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NATURE CHEMISTRY | www.nature.com/naturechemistry 1
SUPPLEMENTARY INFORMATIONDOI: 10.1038/NCHEM.2141
Cresswell, Eey & Denmark S1
Catalytic, Stereospecific Syn-Dichlorination of Alkenes
Alexander J. Cresswell, Stanley T.-C. Eey and Scott E. Denmark*
Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, Illinois 61801
SUPPORTING INFORMATION
TABLE OF CONTENTS PAGE
General Experimental
Literature Preparations
Preparation of Reagents
Preparation of Alkenes
Experimental Procedures
Preparation of Alkenes
Preparation of Diaryl Diselenides
General Procedure I: Reaction Development with Cyclohexene (Table 1)
General Procedure II: Survey of Lewis Base Additives with (E)-1-Benzyloxyl-4-
hexene (17) (Table 2)
General Procedure III: Survey of Diaryl Diselenides with (E)-1-Benzyloxyl-4-
hexene (17) (Table 2)
Table S1. Preliminary Survey of Reaction Generality
General Procedure IV: Preliminary Survey of Reaction Generality (Table S1)
General Procedure V: Control Experiments with (E)-1-Benzyloxyl-4-hexene (17)
General Procedure VI: NMR Spectroscopic Studies on Catalytic,
syn-Dichlorination of Volatile Alkenes
General Procedure VII: Catalytic, syn-Dichlorination of Alkenes with 2,6-Lutidine
N-Oxide as Additive (Table 3)
General Procedure VIII: Catalytic, syn-Dichlorination of Allylic Alcohols (Table 3)
Determination of Relative Configurations Within Dichlorides (Table 3)
S3
S6
S6
S6
S30
S33
S39
S45
S48
S49
S62
S64
S67
S101
S109
Cresswell, Eey & Denmark S1
Catalytic, Stereospecific Syn-Dichlorination of Alkenes
Alexander J. Cresswell, Stanley T.-C. Eey and Scott E. Denmark*
Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, Illinois 61801
SUPPORTING INFORMATION
TABLE OF CONTENTS PAGE
General Experimental
Literature Preparations
Preparation of Reagents
Preparation of Alkenes
Experimental Procedures
Preparation of Alkenes
Preparation of Diaryl Diselenides
General Procedure I: Reaction Development with Cyclohexene (Table 1)
General Procedure II: Survey of Lewis Base Additives with (E)-1-Benzyloxyl-4-
hexene (17) (Table 2)
General Procedure III: Survey of Diaryl Diselenides with (E)-1-Benzyloxyl-4-
hexene (17) (Table 2)
Table S1. Preliminary Survey of Reaction Generality
General Procedure IV: Preliminary Survey of Reaction Generality (Table S1)
General Procedure V: Control Experiments with (E)-1-Benzyloxyl-4-hexene (17)
General Procedure VI: NMR Spectroscopic Studies on Catalytic,
syn-Dichlorination of Volatile Alkenes
General Procedure VII: Catalytic, syn-Dichlorination of Alkenes with 2,6-Lutidine
N-Oxide as Additive (Table 3)
General Procedure VIII: Catalytic, syn-Dichlorination of Allylic Alcohols (Table 3)
Determination of Relative Configurations Within Dichlorides (Table 3)
S3
S6
S6
S6
S30
S33
S39
S45
S48
S49
S62
S64
S67
S101
S109
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General Procedure IX: anti-Selective Dichlorination of Alkenes with Cl2
Determination of Configurations Within Vinylic Chlorides (Figure 2)
Table of Problematic Substrates
References
NMR Spectra
S111
S117
S122
S124
S128
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SUPPLEMENTARY INFORMATIONDOI: 10.1038/NCHEM.2141Cresswell, Eey & Denmark S3
General Experimental
Reaction Setup: All reactions were performed in oven (160 °C) and/or flamed-dried
glassware under an atmosphere of dry argon, unless otherwise indicated. All reported reaction
temperatures correspond to internal temperatures measured with a Teflon coated thermocouple.
Room temperature (rt) was approximately 23 °C. “Brine” refers to a saturated solution of sodium
chloride in H2O.
NMR Spectroscopy: 1H and 13C{1H} NMR spectra were recorded on Varian Unity Inova
400 (400 MHz, 1H; 100 MHz, 13C) or 500 (500 MHz, 1H; 126 MHz, 13C) MHz spectrometers.
Acquisition times were 4.096 s for 1H NMR, and 1.024 s for 13C NMR. Variable temperature
(VT) NMR experiments were performed on a Varian Unity Inova 500 MHz spectrometer
equipped with an external FTS cooling unit (set at 0 °C) for temperature control. Spectra are
referenced to residual chloroform (δ = 7.26 ppm, 1H; 77.00 ppm, 13C) or residual acetonitrile (δ =
1.94 ppm, 1H; 1.32 ppm, 13C). Chemical shifts are reported in parts per million (ppm).
Multiplicities are indicated by s (singlet), d (doublet), t (triplet), q (quartet), pent (pentet), and m
(multiplet). Coupling constants, J, are reported in Hertz. Integration is provided and assignments
are indicated. 1H and 13C assignments are corroborated through 2-D NMR experiments (COSY,
HSQC, HMBC). 1-D NOESY experiments were also used to assign relative configuration in
certain cases.
Infrared Spectroscopy: Infrared (IR) spectra were recorded on a Perkin-Elmer FT-IR
system on NaCl plates. Peaks are reported in cm−1 with indicated relative intensities: s (strong,
0–33% T); m (medium, 34–66% T), w (weak, 67–100% T), and br (broad).
Mass Spectrometry: Mass spectrometry (MS) was performed by the University of Illinois
Mass Spectrometry Laboratory. Electron Impact (EI+) spectra were performed at 70 eV using
methane as the carrier gas, with either a double focusing sector field (DFSF) or time-of-flight
(TOF) mass analyzer. Chemical Ionization (CI+) spectra were performed with methane reagent
gas, with either a double focusing sector field (DFSF) or time-of-flight (TOF) mass analyzer.
Electrospray Ionization (ESI+) spectra were performed using a time-of-flight (TOF) mass
analyzer. Data are reported in the form of m/z (intensity relative to the base peak = 100).
Melting Points: Melting points (mp) were determined on a Thomas-Hoover capillary
melting point apparatus in vacuum-sealed capillary tubes and are corrected.
Elemental Analysis: Elemental analysis was performed by the University of Illinois
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Microanalysis Laboratory or Robertson Microlit Laboratories (1705 U.S. Highway 46, Suite 1D,
Ledgewood, New Jersey 07852, U.S.A.). Reported data is the average of at least 2 runs.
Distillation: Bulb-to-bulb distillation was performed on a Kugelrohr, with boiling points
(bp) corresponding to uncorrected air-bath temperatures (ABT). A vacuum of 10−5 mm Hg was
achieved using a BOC Edwards SI100 diffusion pump.
Chromatography: Analytical thin-layer chromatography was performed on Merck silica
gel 60 F254 or Merck silica gel 60 RP-18 F254s plates. Visualization was accomplished with UV
light and/or potassium permanganate (KMnO4) solution or ceric ammonium molybdate (CAM)
solution. Retention factor (Rf) values reported were measured using a 10 × 2 cm TLC plate in a
developing chamber containing the solvent system (10 mL) described. Flash column
chromatography was performed using Silicycle SiliaFlash® P60 (40-63 µm particle size, 230-400
mesh) (SiO2) or Woelm’s high porosity grade silica. Unless otherwise specified, “SiO2” refers to
P60 grade silica gel. Automated flash column chromatography was performed on a Teledyne
Isco CombiFlash® Rf 200 using pre-packed silica gel columns.
Solvents: Reaction solvents tetrahydrofuran (THF) (Fisher, HPLC grade), ether (Et2O)
(Fisher, BHT stabilized ACS grade), and dichloromethane (CH2Cl2) (Fisher, unstabilized HPLC
grade) were dried by percolation through two columns packed with neutral alumina under a
positive pressure of argon. Reaction solvent toluene (ACS grade) was dried by percolation
through a column packed with neutral alumina and a column packed with Q5 reactant (supported
copper catalyst for scavenging oxygen) under a positive pressure of argon. Reaction solvent
dimethylformamide (DMF) (Fischer, ACS grade) was dried by percolation through two columns
of activated molecular sieves. Reaction solvent acetonitrile (CH3CN) (ACS grade, amylene
stabilized) was distilled from CaH2 prior to use. Reaction solvent ethanol (absolute, Decon
Laboratories) was used as received. Solvents for filtration, transfers, chromatography, and
recrystallization were benzene (PhH) (Fisher, ACS grade), dichloromethane (CH2Cl2) (ACS
grade, amylene stabilized), ether (Et2O) (Fisher, BHT stabilized ACS grade), ethyl acetate
(EtOAc) (Fisher, ACS grade), hexane (Optima), methyl tert-butyl ether (MTBE) (ACS grade),
methanol (MeOH) (ACS grade), pentane (ACS grade), and petroleum ether (35–60°C, ACS
grade).
Chemicals: Cyclohexene (Aldrich) and cycloheptene (Aldrich) were distilled prior to use.
(Z)-4-Hexen-1-ol (Alfa), benzyl bromide (Eastman), chlorotrimethylsilane (Aldrich), 1,1,2,2-
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SUPPLEMENTARY INFORMATIONDOI: 10.1038/NCHEM.2141Cresswell, Eey & Denmark S5
tetrachloroethane, and triethylamine (Aldrich) were distilled from CaH2 prior to use. Sulfolane
(Aldrich) was distilled from 4Å molecular sieves (powder) prior to use. Dimethyl sulfoxide
(DMSO) (Fischer) was dried over 4Å molecular sieves (pellets) prior to use. N-Fluoropyridinium
tetrafluoroborate (11) (TCI), 3-buten-1-ol (Aldrich), 4-N,N′-dimethylaminopyridine (DMAP)
(Aldrich), acetic anhydride (Fisher), benzyltriethylammonium chloride (Oakwood), diphenyl
diselenide (TCI), bis(2-nitrophenyl) diselenide (Acros), selenium powder (Aldrich), imidazole
(Aldrich), (E)-4-octene (GFS Organic), tri-iso-propylsilyl chloride (TIPSCl) (Gelest), tert-
butyldiphenylsilyl chloride (TBDPSCl) (Gelest), m-chloroperbenzoic acid (m-CPBA) (Acros),
cyclopropanecarboxylic acid (Aldrich), N,N’-dicyclohexylcarbodiimide (DCC) (Alfa), 1,1’-
carbonyldiimidazole (CDI) (Aldrich), benzylmagnesium chloride (Aldrich), N,O-
dimethylhydroxylamine hydrochloride (Alfa), ethylene glycol (Aldrich), p-toluenesulfonic acid
(PTSA) monohydrate (Aldrich), oxalyl chloride (Alfa), benzylamine (TCI), sodium hydride
(Aldrich), di-tert-butyl dicarbonate (Boc2O) (Alfa), potassium phthalimide (Aldrich), Red-Al®
(Aldrich), 4-bromoanisole (Aldrich), 2-bromoanisole (Alfa), tert-butyllithium (Aldrich), N-
chlorosuccinimide (NCS) (Aldrich), and triphenylphosphine (Aldrich) were used as received.
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Literature Preparations
Preparation of Reagents
The following compounds were prepared according to literature procedures: 2,6-lutidine
N-oxide (23),1 and bis[3,5-bis(trifluoromethyl)phenyl] diselenide (24).2,3,4
Preparation of Alkenes
The following compounds were prepared according to literature procedures: (E)-4-hexen-
1-ol,5 ethyl (E)-4-hexenoate (28k),5 3-cyclopenten-1-ylmethanol,6 (E)-7-phenylhept-4-en-1-ol,7
4-(but-3-en-1-yl)-2,2-dimethyl-1,3-dioxolane (28e),8 (E)-[(hex-4-en-1-yloxy)methyl]benzene
(17),5 (E)-5-phenylpent-2-en-1-ol (28u),9 (Z)-5-phenylpent-2-en-1-ol (28v),10 (Z)-4-
(benzyloxy)but-2-en-1-ol (28x),11 and (Z)-6-iodo-2-hexene.12
Experimental Procedures
Preparation of Alkenes
Preparation of Cyclopent-3-en-1-ylmethyl acetate (28b)
A 100-mL, round-bottomed flask equipped with a magnetic stirrer bar was charged with
4-N,N-dimethylaminopyridine (61.7 mg, 0.50 mmol, 10 mol %) and 3-cyclopenten-1-ylmethanol
(491 mg, 5.00 mmol, 1.0 equiv) then was sealed with a rubber septum and purged with argon via
an inlet needle. CH2Cl2 (25 mL) and triethylamine (1.01 g, 1.39 mL, 10.0 mmol, 2.0 equiv) were
then added sequentially and stirring was commenced. The mixture was cooled in an ice-water
bath and acetic anhydride (1.02 g, 945 µL, 10.0 mmol, 2.0 equiv) was added dropwise via
syringe over ca. 1 min, then the resultant mixture was allowed to warm to rt over 2 h. The
reaction mixture was then transferred to a separatory funnel and brine (10 mL) and H2O (10 mL)
were added. The layers were separated and the aqueous layer was extracted with CH2Cl2 (2 × 10
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mL). The combined organic extracts were washed sequentially with sat. aq. NaHCO3 (40 mL)
and sat. aq. CuSO4 (40 mL), then dried (MgSO4), filtered, and concentrated in vacuo (45 °C, 120
mm Hg) to give a colorless oil (1.03 g). Purification via flash column chromatography (40 g
SiO2, 30 mm Ø, wet loaded, 97:3 hexane/MTBE, ca. 5 mL fractions) gave a colorless oil (750
mg). Further purification via Kugelrohr distillation at reduced pressure (20 mm Hg) gave 28b as
a clear, colorless oil (488 mg, 70%).
Data for 28b:
bp: 80 °C (ABT) (20 mm Hg) 1H NMR: (500 MHz, CDCl3)
5.67–5.62 (m, 2 H, HC(1,5)), 3.97 (d, J = 7.3 Hz, 2 H, C(3)CH2OAc), 2.64–2.54 (m,
1 H, HC(3)), 2.52–2.43 (m, 2 H, HC(2,4)), 2.13–2.01 (m, 5 H, HC(2,4), COMe) 13C NMR: (126 MHz, CDCl3)
171.1 (COMe), 129.2 (C(1,5)), 68.1 (C(3)CH2OAc), 35.8 (C(3)), 35.6 (C(2,4)),
20.9 (COMe)
IR: (neat)
3056 (w), 2937 (m), 2850 (m), 1743 (s), 1616 (w), 1467 (w), 1443 (m), 1385 (m),
1365 (m), 1237 (s), 1079 (w), 1036 (m), 978 (w), 952 (w), 905 (w), 828 (w), 773
(w), 679 (m), 632 (w), 773 (w), 679 (m), 632 (w), 605 (w)
MS: (CI+, DFSF)
141.1 ([M+H]+, 0.6), 81.1 ([M–OAc]+, 100)
TLC: Rf 0.13 (95:5 hexane/MTBE) [KMnO4]
HRMS: (CI+, DFSF)
calcd for C8H13O2 ([M+H]+): 141.0916, found: 141.0915
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Preparation of tert-Butyl(cyclopent-3-en-1-ylmethoxy)diphenylsilane (28c)
A flame-dried, 50-mL, round-bottomed flask equipped with a magnetic stirrer bar was
charged with 3-cyclopenten-1-ylmethanol (491 mg, 5.00 mmol, 1.0 equiv) and imidazole (518
mg, 7.61 mmol, 1.5 equiv) then was sealed with a rubber septum and purged with argon via an
inlet needle. CH2Cl2 (12.5 mL) was then added and stirring was commenced. tert-
Butyldiphenylsilyl chloride (1.51 g, 1.43 mL, 5.50 mmol, 1.1 equiv) was added dropwise via
syringe and the resultant cloudy mixture was stirred under argon at rt for 16 h. The reaction
mixture was quenched with H2O (20 mL), diluted with CH2Cl2 (10 mL), then was transferred to
a separatory funnel and the layers were separated. The aqueous layer was extracted with CH2Cl2
(2 × 20 mL) and the combined organic extracts were washed with brine (20 mL), dried (MgSO4),
filtered, and concentrated in vacuo (20–23 °C, ca. 20 mm Hg) to give a colourless oil.
Purification via flash column chromatography [72 g high porosity grade SiO2, 34 mm Ø, wet
loaded, petroleum ether (900 mL), ca. 20 mL fractions] gave 28c as a clear, colorless oil (1.61 g,
96%). The 1H and 13C NMR spectroscopic data matched that for alternative preparations.13
Data for 28c: 1H NMR: (500 MHz, CDCl3)
δ 7.72–7.66 (m, 4 H, HC(2′,2′′)), 7.47–7.36 (m, 6 H, HC(3′,3′′,4′,4′′)), 5.68–5.64 (m,
2 H, HC(3,4)), 3.59 (d, J = 7.1 Hz, 2 H, HC(6)), 2.62–2.51 (m, 1 H, HC(1)), 2.49–
2.41 (m, 2 H, HC(2,5)), 2.21–2.12 (m, 2 H, HC(2,5)), 1.07 (s, 9 H, Sit-Bu) 13C NMR: (126 MHz, CDCl3)
δ 135.6 (C(2′,2′′)), 134.1 (C(1′,1′′)), 129.6 (C(4′,4′′)), 129.5 (C(3,4)), 127.6
(C(3′,3′′)), 67.7 (C(6)), 39.4 (C(1)), 35.5 (C(2,5)), 26.9 (SiCMe3), 19.3 (SiCMe3)
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Preparation of (But-3-en-1-yloxy)(tert-butyl)diphenylsilane (28d)
A 25-mL, round-bottomed flask equipped with a magnetic stirrer bar was charged with
imidazole (309 mg, 4.50 mmol, 1.5 equiv) and 3-buten-1-ol (225 mg, 3.00 mmol, 1.0 equiv) then
was sealed with a rubber septum and purged with argon via an inlet needle. CH2Cl2 (6.0 mL) was
then added and stirring was commenced. tert-Butyldiphenylsilyl chloride (922 mg, 872 µL, 3.30
mmol, 1.1 equiv) was added via syringe in one portion and the resultant mixture was stirred
under argon at rt for 22 h. The reaction mixture was then transferred to a separatory funnel and
diluted with CH2Cl2 (25 mL), washed sequentially with H2O (10 mL) and brine (10 mL), then
dried (MgSO4), filtered, and concentrated in vacuo (45 °C, ca. 5 mm Hg) to give a colorless oil
(1.14 g). Purification via flash column chromatography (40 g SiO2, 30 mm Ø, wet loaded, 98:2
hexane/MTBE, ca. 5 mL fractions) gave a colorless oil (975 mg). Further purification via
Kugelrohr distillation at reduced pressure (10–5 mm Hg) gave 28d as a clear, colorless oil (931
mg, quant). The 1H and 13C NMR spectroscopic data matched that for alternative preparations.14
Data for 28d:
bp: 125 °C (ABT) (10–5 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.73–7.69 (m, 4 H, HC(4′,4′′)), 7.47–7.38 (m, 6 H, HC(3′,3′′,4′,4′′)), 5.87 (ddt, J =
17.1, 10.2, 6.9 Hz, 1 H, HC(3)), 5.12–5.03 (m, 2 H, HC(4)), 3.75 (t, J = 6.7 Hz, 2 H,
HC(1)), 2.36 (qt, J = 6.7, 1.3 Hz, 2 H, HC(2)), 1.09 (s, 9 H, Sit-Bu) 13C NMR: (126 MHz, CDCl3)
δ 135.6 (C(2′,2′′)), 135.4 (C(3)), 133.9 (C(1′,1′′)), 129.5 (C(4′,4′′)), 127.6 (C(3′,3′′)),
116.4 (C(4)), 63.5 (C(1)), 37.2 (C(2)), 26.8 (SiCMe3), 19.2 (SiCMe3)
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Preparation of (Z)-[(Hex-4-en-1-yloxy)methyl]benzene (28h)
A flame-dried, 25-mL, Schlenk flask equipped with a magnetic stirrer bar and water-
jacketed reflux condensor was charged sequentially with (Z)-4-hexen-1-ol (620 mg, 723 µL, 6.00
mmol, 1.0 equiv) and THF (10 mL). The solution was cooled in an ice-water bath and NaH
(washed, 158 mg, 6.60 mmol, 1.1 equiv) was added against a backflow of argon, and the
resultant mixture was stirred in the ice-water bath for 15 min. Benzyl bromide (1.13 g, 785 µL,
6.60 mmol, 1.1 equiv) was then added via syringe in one portion and the resultant mixture was
stirred at reflux for 14 h. After being allowed to cool to rt, the reaction was quenched by addition
of sat. aq. NH4Cl (2.0 mL). H2O (20 mL) and EtOAc (20 mL) were then added and the layers
were separated. The aqueous layer was extracted with EtOAc (2 × 20 mL) and the combined
organic extracts were washed with brine (30 mL) then dried (MgSO4), filtered, and concentrated
in vacuo (45 °C, ca. 5 mm Hg) to give a colorless oil (733 mg). Purification via flash column
chromatography (40 g SiO2, 30 mm Ø, wet loaded, 98:2 hexane/MTBE, ca. 5 mL fractions) gave
a clear, colorless oil (1.13 g). Further purification via Kugelrohr distillation at reduced pressure
(0.01 mm Hg) gave 28h as a clear, colorless oil (1.06 g, 93%, >99:1 dr, contaminated with 2%
regioisomeric terminal alkene impurity). The 1H and 13C NMR spectroscopic data matched that
for alternative preparations.15
Data for 28h:
bp: 100 °C (ABT) (0.01 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.39–7.33 (m, 4 H, HC(2′,3′)), 7.33–7.27 (m, 1 H, HC(4′)), 5.52–5.44 (m, 1 H,
HC(5)), 5.43–5.36 (m, 1 H, HC(4)), 4.52 (s, 2 H, HC(5′)), 3.49 (t, J = 6.5 Hz, 2 H,
HC(1)), 2.15 (app q, J = 7.4 Hz, 2 H, HC(3)), 1.73–1.66 (m, 2 H, HC(2)), 1.62 (ddt,
J = 6.7, 1.9, 0.9 Hz, 3 H, HC(6)) 13C NMR: (126 MHz, CDCl3)
δ 138.6 (C(1′)), 129.9 (C(4)), 128.3 (C(3′)), 127.6 (C(2′)), 127.5 (C(4′)), 124.4
(C(5)), 72.9 (C(5′)), 69.8 (C(1)), 29.5 (C(2)), 23.4 (C(3)), 12.7 (C(6))
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Preparation of (E)-tert-Butyl(hex-4-en-1-yloxy)diphenylsilane (13)
A 25-mL, round-bottomed flask equipped with a magnetic stirrer bar was charged with
imidazole (309 mg, 4.50 mmol, 1.5 equiv) and (E)-4-hexen-1-ol (300 mg, 353 µL, 3.00 mmol,
1.0 equiv) then was sealed with a rubber septum and purged with argon via an inlet needle.
CH2Cl2 (6.0 mL) was then added and stirring was commenced. tert-Butyldiphenylsilyl chloride
(922 mg, 872 µL, 3.30 mmol, 1.1 equiv) was added via syringe in one portion and the resultant
mixture was stirred under argon at rt for 18.5 h. The reaction mixture was then transferred to a
separatory funnel and diluted with CH2Cl2 (25 mL), washed sequentially with H2O (10 mL) and
brine (10 mL), then dried (MgSO4), filtered, and concentrated in vacuo (45 °C, ca. 5 mm Hg) to
give a colorless oil (1.15 g). Purification via flash column chromatography (40 g SiO2, 30 mm Ø,
99:1 hexane/MTBE, ca. 5 mL fractions) gave a colorless oil (1.00 g). Further purification via
Kugelrohr distillation at reduced pressure (10–5 mm Hg) gave 13 as a clear, colorless oil (985 mg,
97%, >99:1 dr).
Data for 13:
bp: 125 °C (ABT) (10–5 mm Hg) 1H NMR: (500 MHz, CDCl3)
7.71–7.66 (m, 4 H, HC(2′,2′′)), 7.46–7.36 (m, 6 H, HC(3′,3′′,4′,4′′), 5.48–5.36 (m, 2
H, HC(4,5)), 3.67 (t, J = 6.4 Hz, 2 H, HC(1)), 2.12–2.05 (m, 2 H, HC(3)), 1.67–
1.58 (m, 5 H, HC(2,6)), 1.06 (s, 9 H, Sit-Bu) 13C NMR: (125 MHz, CDCl3)
135.5 (C(2′,2′′)), 134.1 (C(1′,1′′)), 130.9 (C(4)), 129.4 (C(4′,4′′)), 127.5 (C(3′,3′′)),
125.0 (C(5)), 63.3 (C(1)), 32.4 (C(2)), 28.8 (C(3)), 26.8 (SiCMe3), 19.2 (SiCMe3),
17.9 (C(6))
IR: (neat)
3134 (w), 3070 (m), 3049 (m), 3016 (m), 2998 (w), 2931 (s), 2857 (s), 2736 (w),
1958 (w), 1888 (w), 1823 (w), 1654 (w), 1589 (w), 1486 (w), 1472 (m), 1462 (w),
1448 (w), 1427 (m), 1389 (w), 1361 (w), 1305 (w), 1260 (w), 1225 (w), 1188 (w),
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1111 (s), 1042 (w), 1007 (w), 998 (w), 964 (m), 939 (w), 911 (w), 823 (m), 739 (m),
701 (s), 687 (m), 613 (m)
MS: (CI+, DFSF)
339.2 ([M+H]+, 4), 282.1 (24), 281.1 ([M–t-Bu]+, 100), 269.1 (14), 262.1 (16),
261.1 ([M–Ph]+, 72), 253.1 (27), 239.1 (12), 233.1 (14), 219.1 (10), 199.0 (15),
183.0 (10), 91.1 (23), 83.1 (22), 59.1 (33)
TLC: Rf 0.49 (95:5 hexane/MTBE) [KMnO4]
HRMS: (CI+, DFSF)
calcd for C22H31OSi ([M+H]+): 339.2144, found: 339.2128
Preparation of (Z)-tert-Butyl(hex-4-en-1-yloxy)diphenylsilane (28i)
A 25-mL, round-bottomed flask equipped with a magnetic stirrer bar was charged with
imidazole (309 mg, 4.50 mmol, 1.5 equiv) and (Z)-4-hexen-1-ol (310 mg, 361 µL, 3.00 mmol,
1.0 equiv) then was sealed with a rubber septum and purged with argon via an inlet needle.
CH2Cl2 (6.0 mL) was then added and stirring was commenced. tert-Butyldiphenylsilyl chloride
(922 mg, 872 µL, 3.30 mmol, 1.1 equiv) was added via syringe in one portion and the resultant
mixture was stirred under argon at rt for 18.5 h. The reaction mixture was then transferred to a
separatory funnel and diluted with CH2Cl2 (25 mL), washed sequentially with H2O (10 mL) and
brine (10 mL), then dried (MgSO4), filtered, and concentrated in vacuo (45 °C, ca. 5 mm Hg) to
give a colorless oil (1.19 g). Purification via flash column chromatography (40 g SiO2, 30 mm Ø,
wet loaded, 99:1 hexane/MTBE, ca. 5 mL fractions) gave a colorless oil (1.06 g). Further
purification via Kugelrohr distillation at reduced pressure (10–5 mm Hg) gave 28i as a clear,
colorless oil (1.02 g, quant, >99:1 dr).
Data for 28i:
bp: 125 °C (ABT) (10–5 mm Hg) 1H NMR: (500 MHz, CDCl3)
7.73–7.69 (m, 4 H, HC(2′,2′′)), 7.47–7.38 (m, 6 H, HC(3′,4′′)), 5.52–5.35 (m, 2 H,
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HC(4,5)), 3.71 (t, J = 6.4 Hz, 2 H, HC(1)), 2.17 (q, J = 7.3 Hz, 2 H, HC(3)), 1.68–
1.61 (m, 5 H, HC(2,6)), 1.09 (s, 9 H, Sit-Bu) 13C NMR: (125 MHz, CDCl3)
135.5 (C(2′,2′′)), 134.0 (C(1′,1′′)), 130.1 (C(4)), 129.4 (C(4′,4′′)), 127.5 (C(3′,3′′)),
124.1 (C(5)), 63.4 (C(1)), 32.4 (C(2)), 26.8 (SiCMe3), 23.1 (C(3)), 19.2 (SiCMe3),
12.7 (C(6))
IR: (neat)
3135 (w), 3070 (m), 3049 (w), 3013 (m), 2931 (s), 2858 (s), 2739 (w), 1957 (w),
1886 (w), 1824 (w), 1655 (w), 1589 (w), 1486 (w), 1472 (m), 1462 (w), 1446 (w),
1403 (w), 1389 (w), 1361 (w), 1305 (w), 1259 (w), 1222 (w), 1189 (w), 1111 (s),
1043 (w), 1006 (w), 998 (w), 960 (w), 940 (w), 823 (m), 739 (m), 701 (s), 688 (m),
613 (m)
MS: (CI+, DFSF)
339.2 ([M+H]+, 5), 282.1 (23), 281.1 ([M–t-Bu]+, 100), 262.1 (17), 261.1 ([M–Ph]+,
80), 239.1 (12), 199.0 (15), 83.1 (30)
TLC: Rf 0.50 (95:5 hexane/MTBE) [KMnO4]
HRMS: (FAB+, DFSF)
calcd for C22H31OSi ([M+H]+): 339.2144, found: 339.2129
Preparation of (E)-Tri-iso-propyl[(7-phenylhept-4-en-1-yl)oxy]silane (28j)
A flame-dried, 50-mL, round-bottomed flask equipped with a magnetic stirrer bar was
charged with (E)-7-phenylhept-4-en-1-ol (951 mg, 5.00 mmol, 1.0 equiv) and imidazole (515
mg, 7.56 mmol, 1.5 equiv) then was sealed with a rubber septum and purged with argon via an
inlet needle. CH2Cl2 (12.5 mL) was then added and stirring was commenced. Tri-iso-propylsilyl
chloride (1.08 g, 1.20 mL, 5.61 mmol, 1.1 equiv) was added dropwise via syringe and the
resultant mixture was stirred under argon at rt for 16 h. The reaction mixture was quenched with
H2O (20 mL), diluted with CH2Cl2 (10 mL), then transferred to a separatory funnel and the layers
were separated. The aqueous layer was extracted with CH2Cl2 (2 × 20 mL) and the combined
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organic extracts were washed with brine (20 mL), dried (MgSO4), filtered, and concentrated in
vacuo (20–23 °C, ca. 20 mm Hg) to give a pale yellow oil. Purification via flash column
chromatography [71 g high porosity grade SiO2, 34 mm Ø, wet loaded, 100:0 → 98:2
hexane/EtOAc (200 and 900 mL, respectively), ca. 20 mL fractions] gave 28j as a clear,
colorless oil (1.69 g, 98%, >99:1 dr). An analytically pure sample was obtained by further
purification of 28j (219 mg) via flash column chromatography [27 g SiO2, 24 mm Ø, wet loaded
with hexane, 98:2 hexane/EtOAc (400 mL), ca. 10 mL fractions], followed by Kugelrohr
distillation at reduced pressure (0.05 mm Hg), to give 28j as a clear, colorless oil (214 mg, 98%
mass return).
Data for 28j: bp: 158 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.31–7.25 (m, 2 H, HC(2′)), 7.21–7.16 (m, 3 H, HC(3′,4′)), 5.51–5.42 (m, 2 H,
HC(4,5)), 3.67 (t, J = 6.5 Hz, 2 H, HC(1)), 2.70–2.63 (m, 2 H, HC(7)), 2.34–2.27
(m, 2 H, HC(6)), 2.06 (q, J = 7.0, 6.3 Hz, 2 H, HC(3)), 1.59 (app pent, J = 6.6 Hz, 2
H, HC(2)), 1.13–1.02 (m, 21 H, Sii-Pr3) 13C NMR: (126 MHz, CDCl3)
δ 142.2 (C(1′)), 130.6 & 129.6 (C(4,5)), 128.4 (C(2′)), 128.2 (C(3′)), 125.7 (C(4′)),
62.8 (C(1)), 36.1 (C(7)), 34.5 (C(6)), 32.8 (C(2)), 28.8 (C(3)), 18.0 (SiCH(CH3)2),
12.0 (SiCH(CH3)2)
IR: (neat)
3086 (w), 3063 (w), 3028 (w), 2941 (s), 2893 (m), 2865 (s), 2726 (w), 1605 (w),
1497 (w), 1463 (m), 1455 (w), 1383 (w), 1366 (w), 1247 (w), 1108 (m), 1070 (w),
1031 (w), 1013 (w), 996 (w), 967 (m), 919 (w), 883 (w), 785 (w), 744 (w), 698 (m),
681 (m), 659 (w)
MS: (ESI+, TOF)
403.4 (14), 390.4 (32), 389.3 (75), 347.3 ([M+H]+, 4), 231.2 (11), 230.2 (34), 229.2
(100), 215.2 (21), 175.2 (12), 174.2 (29), 173.3 (53), 173.1 (91), 157.2 (21), 131.1
(17)
HRMS: (ESI+, TOF)
calcd for C22H39OSi ([M+H]+): 347.2770, found: 347.2778
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TLC: Rf 0.56 (99:1 hexane/MTBE) [UV/KMnO4]
Analysis: C22H38OSi (346.63)
Calcd: C, 76.23; H, 11.05%
Found: C, 76.38; H, 11.22%
Preparation of (E)-Hex-4-en-1-yl cyclopropanecarboxylate (28l)
A flame-dried, 50-mL, round-bottomed flask equipped with a magnetic stirrer bar was
charged with 4-N,N-dimethylaminopyridine (74 mg, 0.61 mmol, 10 mol %) then was sealed with
a rubber septum and purged with argon via an inlet needle. Et2O (6 mL), cyclopropanecarboxylic
acid (519 mg, 0.48 mL, 6.03 mmol, 1.0 equiv), and (E)-4-hexen-1-ol (639 mg, 0.75 mL, 6.37
mmol, 1.05 equiv) were sequentially added via syringe. The mixture was then cooled in an ice-
water bath and stirring was commenced. N,N′-Dicyclohexylcarbodiimide (1.36 g, 6.60 mmol, 1.1
equiv) was added in one portion against a backflow of argon and the resultant mixture was
stirred in the ice-water bath and allowed to gradually warm to rt over 18 h to give a thick, white
slurry. The reaction mixture was filtered through a pad of Celite (10 g, 35 mm) under house
vacuum to remove the urea by-product, which was rinsed with Et2O (50 mL). The filtrate was
concentrated in vacuo (20–23 °C, ca. 20 mm Hg) to give a pale yellow oil. Caution: the product
is volatile and should not be left on the rotary evaporator for an extended period. Purification
via flash column chromatography [90 g SiO2, 42 mm Ø, wet loaded with hexane, 96:4
hexane/EtOAc (1 L), ca. 20 mL fractions] gave a clear, pale yellow oil (1.03 g). Further
purification via Kugelrohr distillation at reduced pressure (10 mm Hg) gave 28l as a clear,
colorless oil (994 mg, 98%, >99:1 dr).
Data for 28l: bp: 81 °C (ABT) (10 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 5.49–5.36 (m, 2 H, HC(4,5)), 4.06 (t, J = 6.7 Hz, 2 H, HC(1)), 2.05 (dt, J = 7.5,
6.7 Hz, 2 H, HC(3)), 1.71–1.62 (m, 5 H, HC(2,6)), 1.59 (ddd, J = 12.7, 8.1, 4.6 Hz,
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1 H, HC(8)), 1.00–0.96 (m, 2 H, HC(9,10)), 0.86–0.81 (m, 2 H, HC(9,10)) 13C NMR: (126 MHz, CDCl3)
δ 174.9 (C(7)), 130.0 & 125.8 (C(4,5)), 64.0 (C(1)), 28.8 (C(3)), 28.5 (C(2)), 17.9
(C(6)), 12.9 (C(8)), 8.3 (C(9,10))
IR: (neat)
3387 (w), 3021 (w), 2938 (w), 2853 (w), 1729 (m), 1451 (w), 1403 (w), 1372 (w),
1266 (w), 1172 (m), 1135 (s), 1106 (m), 996 (w), 967 (w), 914 (w), 615 (m)
MS: (CI+, DFSF)
169.1 ([M+H]+, 2), 135.0 (11), 83.1 (39), 82.1 (26), 69.0 (22), 67.0 (16), 65.0 (32),
63.0 (100), 62.0 (25), 61.0 (13), 59.0 (57)
HRMS: (EI+, DFSF)
calcd for C10H17O2 ([M+H]+): 169.12286, found: 169.12251
TLC: Rf 0.45 (96:4 hexane/EtOAc) [KMnO4]
Preparation of (E)-2-Benzyl-2-(pent-3-en-1-yl)-1,3-dioxolane (28m)
Preparation of (E)-4-hexenoic acid (S1). An oven-dried, 50-mL, round-bottomed flask
equipped with a magnetic stirrer bar was charged sequentially with ethyl (E)-4-hexenoate (28k)
(1.42 g, 10.0 mmol, 1.0 equiv), EtOH (6.0 mL), H2O (6.0 mL), and NaOH (2.31 g, 57.8 mmol,
5.8 equiv) then was fitted with a water-jacketed condenser (sealed with a rubber septum at the
top) and purged with argon via an inlet needle. Stirring was commenced and the reaction mixture
was refluxed at 98–100 °C (oil bath temperature) for 3 h, then was allowed to cool to rt. The
reaction mixture was diluted with H2O (20 mL) and transferred to a separatory funnel, then
extracted with Et2O (3 × 10 mL). The combined organic extracts were discarded and the aqueous
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layer was then cooled in an ice-water bath, acidified with 2 M HCl to pH 2 (with stirring),
transferred to a separatory funnel, and extracted with CH2Cl2 (3 × 20 mL). The combined
organic extracts were washed with H2O (20 mL) and brine (20 mL), then dried (MgSO4),
filtered, and concentrated in vacuo (20–23 °C, ca. 20 mm Hg) to give a colorless oil. Purification
via Kugelrohr distillation at reduced pressure (10 mm Hg) gave S1 as a clear, colorless oil (1.12
g, 98%, >99:1 dr). The 1H NMR spectroscopic data matched that reported in the literature.16
Data for S1:
bp: 145 °C (ABT) (10 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 11.86 (br s, 1 H, COOH), 5.54–5.39 (m, 2 H, HC(4,5)), 2.41 (ddd, J = 7.9, 7.1,
1.0 Hz, 2 H, HC(2)), 2.34–2.25 (m, 2 H, HC(3)), 1.64 (dq, J = 6.3, 1.3 Hz, 3 H,
HC(6)) 13C NMR: (126 MHz, CDCl3)
δ 180.0 (C(1)), 128.8 (C(4)), 126.4 (C(5)), 34.1 (C(2)), 27.5 (C(3)), 17.8 (C(6))
Preparation of (E)-N-Methoxy-N-methylhex-4-enamide (S2). A flame-dried, 50-mL,
round-bottomed flask equipped with a magnetic stirrer bar was charged with (E)-4-hexenoic acid
(S10) (572 mg, 5.01 mmol, 1.0 equiv) then was sealed with a rubber septum and purged with
argon via an inlet needle. CH2Cl2 (14 mL) was added and stirring was commenced. The mixture
was cooled in an ice-water bath and 1,1′-carbonyldiimidazole (977 mg, 6.02 mmol, 1.2 equiv)
was added in one portion against a backflow of argon, and the resultant mixture was stirred in the
ice-water bath for 30 min. N,O-Dimethylhydroxylamine hydrochloride (1.22 g, 12.5 mmol, 2.5
equiv) was then added in one portion against a backflow of argon. The reaction flask was
removed from the ice-water bath and the resultant mixture was allowed to warm to rt over 7 h.
The reaction mixture was then filtered through a sintered funnel under house vacuum to remove
the amine salt, which was rinsed with CH2Cl2 (50 mL). The filtrate was transferred to a
separatory funnel and the organic layer was washed sequentially with 2 M HCl (30 mL), 2 M
NaOH (30 mL), and brine (30 mL), then dried (MgSO4), filtered, and concentrated in vacuo (20–
23 °C, ca. 20 mm Hg) to give a colorless oil. Purification via Kugelrohr distillation at reduced
pressure (130 °C, 5 mm Hg) gave S2 as a clear, colorless oil (782 mg, 99%, >99:1 dr). The 1H
and 13C NMR spectroscopic data matched that for alternative preparations.17
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Data for S2:
bp: 130 °C (ABT) (5 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 5.52–5.37 (m, 2 H, HC(4,5)), 3.65 (s, 3 H, N(Me)OMe), 3.15 (s, 3 H,
N(Me)OMe), 2.45 (t, J = 7.4 Hz, 2 H, HC(4)), 2.34–2.19 (m, 2 H, HC(3)), 1.66–
1.55 (m, 3 H, HC(6)) 13C NMR: (126 MHz, CDCl3)
δ 174.0 (C(1)), 129.8 (C(4)), 125.6 (C(5)), 61.1 (N(Me)OMe), 32.0 (N(Me)OMe)),
31.8 (C(2)), 27.4 (C(3)), 17.9 (C(6))
Preparation of (E)-1-Phenylhept-5-en-2-one (S3). A flame-dried, 50-mL, round-
bottomed flask equipped with a magnetic stirrer bar was charged with (E)-N-methoxy-N-
methylhex-4-enamide (S2) (629 mg, 4.00 mmol, 1.0 equiv) then was sealed with a rubber septum
and purged with argon via an inlet needle. THF (14 mL) was added and stirring was commenced.
The mixture was cooled in an ice-water bath (bath temperature ca. 0 °C) and benzylmagnesium
chloride (2.0 M in THF, 4.2 mL, 8.40 mmol, 2.1 equiv) was slowly added via syringe under an
argon atmosphere over 5 min. The resultant yellow-brown mixture was allowed to stir in the ice-
water bath and gradually warm to rt over 20 h, then was re-cooled in an ice-water bath and
carefully quenched with 2 M HCl (20 mL). The mixture was transferred to a separatory funnel
and the aqueous layer was extracted with Et2O (3 × 20 mL). The combined organic extracts were
washed with brine (20 mL) then dried (MgSO4), filtered, and concentrated in vacuo (20–23 °C,
ca. 20 mm Hg) to give a yellow oil. Purification via flash column chromatography [37 g SiO2, 30
mm Ø, dry loaded with 2 g SiO2, 100:0 → 98:2 → 95:5 hexane/Et2O (200 mL, 300 mL, and 300
mL, respectively), ca. 10 mL fractions], followed by further purification via flash column
chromatography under the same conditions, gave S3 as a clear, pale yellow oil (455 mg, 60%,
>99:1 dr). Caution: the product is volatile at ca. 0.05 mm Hg – some material was lost as a
result.
Data for S3:
1H NMR: (500 MHz, CDCl3)
δ 7.35–7.31, 7.29–7.24 & 7.22–7.18 (m, 5 H, HC(2′,3′,4′)), 5.45–5.31 (m, 2 H,
HC(5,6)), 3.68 (s, 2 H), 2.50 (t, J = 7.4 Hz, 2 H, HC(3)), 2.26–2.20 (m, 2 H, HC(4)),
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1.61 (dd, J = 6.0, 1.2 Hz, 3 H, HC(7)) 13C NMR: (126 MHz, CDCl3)
δ 207.8 (C(2)), 134.2 (C(1′)), 129.38 (C(2′)), 129.37 (C(5)), 128.7 (C(3′)), 126.9
(C(4′)), 125.9 (C(6)), 50.2 (C(1)), 41.8 (C(3)), 26.7 (C(4)), 17.8 (C(7))
IR: (neat)
3063 (w), 3028 (m), 2959 (w), 2918 (m), 2855 (w), 1714 (s), 1603 (w), 1585 (w),
1496 (m), 1454 (m), 1408 (w), 1361 (w), 1315 (w), 1189 (w), 1113 (w), 1075 (w),
1031 (w), 967 (m), 732 (w), 699 (m)
MS: (ESI+, TOF)
217.1 (12), 216.1 (34), 211.1 ([M+Na]+, 29), 208.1 (85), 206.2 (12), 190.1 (14),
189.1 ([M+H]+, 100), 143.6 (19), 134.6 (21), 119.1 (15), 91.1 ([CH2Ph]+, 45)
HRMS: (ESI+, TOF)
calcd for C13H17O ([M+H]+): 189.1279, found: 189.1285
TLC: Rf 0.28 (96:4 hexane/EtOAc) [UV/KMnO4]
Preparation of (E)-2-Benzyl-2-(pent-3-en-1-yl)-1,3-dioxolane (28m). A flame-dried,
50-mL, round-bottomed flask equipped with a magnetic stirrer bar was charged with (E)-1-
phenylhept-5-en-2-one (S3) (390 mg, 2.07 mmol, 1.0 equiv) and p-toluenesulfonic acid
monohydrate (8.2 mg, 0.04 mmol, 2 mol %) then was sealed with a rubber septum and purged
with argon via an inlet needle. Toluene (20 mL) and ethylene glycol (1.11 g, 1.0 mL, 17.9 mmol,
8.6 equiv) were added sequentially, then the rubber septum was replaced with a Dean-Stark trap
fitted with a condenser (sealed at the top with a rubber septum), and the apparatus was purged
with argon via an inlet needle. The resultant mixture was refluxed at 148–149 °C (oil bath
temperature) for 24 h (N.B. ca. 0.9 mL H2O was collected in the receiver of the Dean-Stark trap
at the end of the reaction). The reaction mixture was then allowed to cool to rt and was
transferred to a separatory funnel and diluted with Et2O (20 mL). The organic phase was washed
sequentially with sat. aq. NaHCO3 (2 × 10 mL) and brine (10 mL), then dried (MgSO4), filtered,
and concentrated in vacuo (20–23 °C, ca. 20 mm Hg) to give a pale yellow oil. Purification via
flash column chromatography [26 g SiO2, 24 mm Ø, dry loaded with 1.9 g SiO2, 97:3
hexane/EtOAc (400 mL), ca. 10 mL fractions)], followed by further purification via flash column
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chromatography under the same conditions, gave 28m as a clear, colourless oil (461 mg, 96%,
>99:1 dr). An analytically pure sample was obtained by further purification of 28m (216 mg) via
Kugelrohr distillation at reduced pressure (0.05 mm Hg) to give 28m as a clear, colourless oil
(211 mg, 98% mass return).
Data for 28m: bp: 100 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.30–7.25 & 7.25–7.20 (m, 5 H, HC(2′,3′,4′)), 5.47–5.35 (m, 2 H, HC(5,6)), 3.90–
3.83 (m, 2 H, HC(8,9)), 3.73–3.66 (m, 2 H, HC(8,9)), 2.89 (s, 2 H, HC(1)), 2.14–
2.06 (m, 2 H, HC(4)), 1.69–1.64 (m, 2 H, HC(3)), 1.64–1.61 (m, 3 H, HC(7)) 13C NMR: (126 MHz, CDCl3)
δ 136.8 (C(1′)), 130.9 (C(5)), 130.5 (C(2′)), 127.9 (C(3′)), 126.3 (C(4′)), 124.8
(C(6)), 111.1 (C(2)), 65.3 (C(8,9)), 43.9 (C(1)), 37.8 (C(3)), 26.6 (C(4)), 17.9
(C(7))
IR: (neat)
3086 (w), 3063 (w), 3029 (m), 2953 (m), 2922 (m), 2884 (m), 2856 (m), 1605 (w),
1496 (m), 1475 (m), 1454 (w), 1377 (w), 1324 (w), 1258 (w), 1198 (m), 1124 (m),
1077 (m), 1048 (m), 967 (m), 950 (m), 851 (w), 751 (m), 700 (m), 671 (w), 640 (w),
617 (w)
MS: (ESI+, TOF)
284.3 (34), 282.3 (24), 256.3 (26), 249.2 (13), 233.2 ([M+H]+, 35), 231.2 (11),
190.1 (13), 189.1 ([M–(CH2CH2O)+H]+, 84), 187.1 (18), 171.1 (32), 163.1 ([M–
(CH3CH=CHCH2CH2)]+, 59), 141.1 ([M–(CH2Ph)]+, 20), 129.1 (20), 124.1 (24),
119.1 (30), 99.1 (12), 91.1 ([CH2Ph]+, 100)
HRMS: (ESI+, TOF)
calcd for C15H21O2 ([M+H]+): 233.1542, found: 233.1547
TLC: Rf 0.36 (96:4 hexane/EtOAc) [UV/KMnO4]
Analysis: C15H20O2 (232.32)
Calcd: C, 77.55; H, 8.68%
Found: C, 77.97; H, 8.67%
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Preparation of Methyl (2E,6E)-Octa-2,6-dienoate (28n)
A flame-dried, 100-mL, round-bottomed flask equipped with a magnetic stirrer bar and
rubber septum was purged with argon via an inlet needle then was charged sequentially with
CH2Cl2 (25 mL) and oxalyl chloride (1.14 g, 0.76 mL, 8.98 mmol, 1.5 equiv) via syringe, and
stirring was commenced. The solution was cooled at –78 °C in a dry ice-acetone bath under an
argon atmosphere, then anhydrous DMSO (1.43 g, 1.3 mL, 18.3 mmol, 3.0 equiv) was added
dropwise via syringe over 5 min, and the resultant mixture was allowed to stir at –78 °C for a
further 5 min. (E)-4-Hexen-1-ol (604 mg, 0.71 mL, 6.03 mmol, 1.0 equiv) was then added via
cannula transfer over 10 min using two portions of CH2Cl2 (4 mL and 2 mL), and the resultant
white suspension was stirred at –78 °C for 30 min. Triethylamine (3.66 g, 5.0 mL, 36.1 mmol,
6.0 equiv) was then added via syringe and the mixture was allowed to warm to –5 °C with
stirring over 2 h, then the dry ice-acetone bath was replaced with an ice-water bath. A solution of
methyl(triphenylphosphoranylidene)acetate (4.02 g, 12.0 mmol, 2.0 equiv) in CH2Cl2 (10 mL)
was then transferred into the reaction mixture via cannula, and the resultant mixture was allowed
to stir in the ice-water bath and gradually warm to rt over 20 h. The mixture was then transferred
to a separatory funnel containing H2O (50 mL) and the aqueous layer was extracted with Et2O (3
× 30 mL). The combined organic layers were washed with brine (30 mL), then dried (MgSO4),
filtered, and concentrated in vacuo (20–23 °C, ca. 20 mm Hg) to give a thick, yellow paste (95:5
E/Z). Caution: the product is volatile and should not be left on the rotary evaporator for an
extended period. Purification via flash column chromatography [66 g SiO2, 34 mm Ø, dry
loaded, 99:1 hexane/Et2O (1.2 L), ca. 20 mL fractions then 28 g SiO2, 24 mm Ø, wet loaded,
100:0 → 99:1 hexane/EtOAc (100 mL and 500 mL, respectively), ca. 10 mL fractions] gave a
colourless oil (785 mg). Further purification via Kugelrohr distillation at reduced pressure (5 mm
Hg) gave 28n as a clear, colourless oil (772 mg, 83%, >99:1 dr).
Data for 28n: bp: 81 °C (ABT) (5 mm Hg)
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1H NMR: (500 MHz, CDCl3)
δ 6.96 (dt, J = 15.7, 6.8 Hz, 1 H, HC(3)), 5.82 (dt, J = 15.7, 1.6 Hz, 1 H, HC(2)),
5.50–5.36 (m, 2 H, HC(6,7)), 3.72 (s, 3 H, CO2Me), 2.25 (q, J = 7.5 Hz, 2 H,
HC(4)), 2.13 (q, J = 6.7 Hz, 2 H, HC(5)), 1.64 (dt, J = 6.2, 1.3 Hz, 3 H, HC(8)) 13C NMR: (126 MHz, CDCl3)
δ 167.1 (C(1)), 149.0 (C(3)), 129.5 (C(6)), 126.1 (C(7)), 121.0 (C(2)), 51.4
(CO2Me), 32.2 (C(4)), 31.0 (C(5)), 17.9 (C(8))
IR: (neat)
3027 (w), 2993 (w), 2950 (m), 2855 (w), 1727 (s), 1659 (m), 1436 (m), 1378 (w),
1324 (w), 1271 (m), 1203 (m), 1164 (m), 1126 (w), 1041 (m), 967 (m), 852 (w),
718 (w)
MS: (EI+, DFSF)
154.1 (M+, 13), 123.1 ([M–OMe]+, 50), 122.1 (28), 100.0 (100), 95.1 ([M–
CO2Me]+, 46), 94.1 (25), 69.0 ([CH3CH=CHCH2CH2]+, 60), 68.0 (54), 67.0 (23),
55.1 ([CH3CH=CHCH2]+, 100), 53.1 (29)
HRMS: (EI+, DFSF)
calcd for C9H14O2 (M+): 154.09938, found: 154.09916
TLC: Rf 0.53 (92:8 hexane/EtOAc) [UV/KMnO4]
Preparation of tert-Butyl (Z)-benzyl(hex-4-en-1-yl)carbamate (28o)
Preparation of tert-Butyl Benzylcarbamate (S5). A flame-dried, 50-mL, round-
bottomed flask equipped with a magnetic stirrer bar and rubber septum was purged with argon
via an inlet needle, then was charged sequentially with CH2Cl2 (15 mL), benzylamine (647 mg,
660 µL, 6.04 mmol, 1.0 equiv), and triethylamine (944 mg, 1.3 mL, 9.33 mmol, 1.5 equiv) via
syringe, and stirring was commenced. The resultant mixture was cooled in an ice-water bath then
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di-tert-butyl dicarbonate (1.61 g, 1.7 mL, 7.40 mmol, 1.2 equiv) was added via syringe over 2–3
min, and the resultant mixture was allowed to warm to rt over 4 h. The reaction mixture was then
transferred to a separatory funnel, diluted with CH2Cl2 (30 mL), and washed sequentially with
H2O (2 × 20 mL) and brine (20 mL), then dried (MgSO4), filtered, and concentrated in vacuo
(20–23 °C, ca. 20 mm Hg) to give a colourless, viscous oil. Purification via flash column
chromatography [75 g SiO2, 42 mm Ø, dry loaded, 92:8 hexane/EtOAc (1.2 L), ca. 20 mL
fractions] gave S5 as a clear, colourless, viscous oil, which solidified to a white solid on standing
in a –20 °C freezer for ca. 1 day (1.25 g, quant.). The 1H and 13C NMR spectroscopic data
matched that for alternative preparations.18
Data for S5:
1H NMR: (500 MHz, CDCl3)
δ 7.34–7.22 (m, 5 H, HC(2′,3′,4′)), 4.98 (br s, 1 H, NH), 4.30 (d, J = 5.4 Hz, 2 H,
HC(5’)), 1.46 (s, 9 H, Ot-Bu) 13C NMR: (126 MHz, CDCl3)
δ 155.8 (NCO2CMe3), 138.9 (C(1′)), 128.5 (C(3′)), 127.4 (C(4′)), 127.2 (C(2′)),
79.3 (NCO2CMe3), 44.5 (C(5’)), 28.3 (NCO2CMe3)
Preparation of tert-Butyl (Z)-Benzyl(hex-4-en-1-yl)carbamate (28o). An oven-dried,
25-mL, Schlenk flask equipped with a magnetic stirrer bar was charged with NaH (washed, 108
mg, 4.50 mmol, 1.5 equiv) in the glovebox, and was then sealed with a rubber septum and
removed from the box. DMF (7.5 mL) was then added via syringe under an atmosphere of argon
and stirring was commenced. The suspension was cooled in an ice-water bath then tert-butyl
benzylcarbamate S5 (622 mg, 3.00 mmol, 1.0 equiv) was added via cannula transfer using two
portions of DMF (2 × 2.0 mL), and the resultant mixture was stirred in the ice-water bath for 10
min, then was allowed to warm to rt over 30 min at rt (N.B. generation of H2 gas was only
observed when the temperature was elevated). (Z)-6-Iodo-2-hexene (662 mg, 3.15 mmol, 1.05
equiv) was added via syringe using two portions of DMF (2 × 1.0 mL), then the rubber septum
was replaced with a water-jacketed reflux condenser (sealed at the top with a rubber septum).
The mixture was allowed to stir at rt for 30 min then was heated at 70–72 °C (oil bath
temperature) for a further 18 h. Once the reaction had been allowed to cool to rt, it was carefully
quenched with H2O (2 mL), transferred to a separatory funnel, and diluted with H2O (20 mL).
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The aqueous layer was extracted with Et2O (3 × 20 mL) and the combined organic extracts were
washed sequentially with H2O (20 mL) and brine (20 mL), then dried (MgSO4), filtered, and
concentrated in vacuo (20–23 °C, ca. 20 mm Hg) to give a pale yellow oil. Purification via flash
column chromatography [88 g SiO2, 42 mm Ø, dry loaded, 97:3 hexane/EtOAc (1 L), ca. 20 mL
fractions] gave 28o as a clear, colourless oil (718 mg, 83%, >99:1 dr). An analytically pure
sample was obtained by further purification of 28o (279 mg) via flash column chromatography
[28 g SiO2, 24 mm Ø, wet loaded with CH2Cl2, 97:3 hexane/EtOAc (400 mL), ca. 10 mL
fractions] followed by Kugelrohr distillation at reduced pressure (0.05 mm Hg) to give 28o as a
clear, colorless oil (275 mg, >99:1 dr, 99% mass return).
Data for 28o: bp: 158 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, MeCN-d3, VT at 53 °C, calibrated with ethylene glycol)
δ 7.36–7.31 (m, 2 H, HC(2′)), 7.29–7.24 (m, 3 H, HC(3′,4′)), 5.49–5.33 (m, 2 H,
HC(4,5)), 4.42 (s, 2 H, HC(5′)), 3.19 (t, J = 7.4 Hz, 2 H, HC(1)), 2.00 (q, J = 7.3 Hz,
2 H, HC(3)), 1.59–1.51 (m, 5 H, HC(2,6)), 1.45 (s, 3 H, Ot-Bu) 13C NMR: (126 MHz, MeCN-d3, VT at 53 °C, calibrated with ethylene glycol)
[N.B. partial isomerization (ca. 1%) of the (Z)-olefin was observed after heating at
53 °C for 1 h whilst collecting the 13C NMR spectroscopic data]
δ 156.7 (NCO2CMe3), 140.4 (C(1′)), 131.0 (C(4)), 129.5 (C(3′)), 128.5 (C(4′)),
128.1 (C(2′)), 125.2 (C(5)), 80.1 (NCO2CMe3), 51.4 (C(5′)), 47.7 (C(1)), 29.1 &
29.0 (C(2), NCO2CMe3), 25.1 (C(3)), 13.1 (C(6))
IR: (neat)
3011 (w), 2975 (m), 2931 (m), 1696 (s), 1605 (w), 1496 (w), 1453 (m), 1415 (m),
1391 (w), 1365 (m), 1241 (m), 1165 (m), 1134 (m), 1029 (w), 987 (w), 878 (w),
770 (w), 733 (w), 699 (m)
MS: (ESI+, TOF)
312.2 ([M+Na]+, 28), 291.2 (12), 290.2 ([M+H]+, 57), 235.2 (20), 234.2 (100),
164.1 (40), 91.1 ([CH2Ph]+, 30)
HRMS: (ESI+, TOF)
calcd for C18H28NO2 ([M+H]+): 290.2120, found: 290.2119
TLC: Rf 0.24 (96:4 hexane/EtOAc) [UV/KMnO4]
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Analysis: C18H27NO2 (289.42)
Calcd: C, 74.70; H, 9.40; N, 4.84%
Found: C, 74.92; H, 9.44; N, 5.11%
Preparation of (Z)-2-(Hex-4-en-1-yl)isoindoline-1,3-dione (28p)
A flame-dried, 25-mL, Schlenk flask equipped with a magnetic stirrer bar and water-
jacketed reflux condenser was charged with (Z)-6-iodo-2-hexene (630 mg, 3.00 mmol, 1.0 equiv)
and DMF (15 mL) under an argon atmosphere, then stirring was commenced. Potassium
phthalimide (680 mg, 3.60 mmol, 1.2 equiv) was added against a backflow of argon and the
resultant mixture was heated at 90 °C for 14.5 h. The reaction mixture was then allowed to cool
to rt and was transferred to a separatory funnel, then diluted with H2O (75 mL) and EtOAc (50
mL). The layers were separated and the aqueous layer was extracted with EtOAc (2 × 50 mL).
The combined organic extracts were then washed with H2O (5 × 50 mL), dried (MgSO4), filtered,
and concentrated in vacuo (20–23 °C, ca. 20 mm Hg) to give a yellow oil (730 mg). Purification
via flash column chromatography (40 g SiO2, 30 mm Ø, 90:10 hexanes/MTBE, ca. 5 mL
fractions) gave a colourless oil (684 mg). Further purification via Kugelrohr distillation at
reduced pressure (0.01 mm Hg) gave 28p as a clear, colorless oil, which solidified to a white
semi-solid on standing in a –20 °C freezer for ca. 1 day (650 mg, 94%, >99:1 dr, ca. 97% purity,
contaminated with a regioisomeric terminal alkene impurity and an unidentified hydrocarbon
impurity). The 1H NMR spectroscopic data matched that for alternative preparations.19
Data for 28p: bp: 120 °C (ABT) (0.01 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.87–7.81 (m, 2 H, HC(3′)), 7.74–7.68 (m, 2 H, HC(4′)), 5.52–5.34 (m, 2 H,
HC(4,5)), 3.69 (dd, J = 8.1, 6.8 Hz, 2 H, HC(1)), 2.11 (q, J = 7.4 Hz, 2 H, HC(3)),
1.80–1.70 (m, 2 H, HC(2)), 1.60 (ddd, J = 6.6, 1.5, 0.7 Hz, 3 H, HC(6))
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13C NMR: (126 MHz, CDCl3)
δ 168.3 (C(1′)), 133.7 (C(4′)), 132.1 (C(2′)), 129.0 (C(4)), 124.8 (C(5)), 123.0
(C(3′)), 37.6 (C(1)), 28.2 (C(2)), 24.2 (C(3)), 12.7 (C(6))
Preparation of (E)-tert-Butyl(hex-2-en-1-yloxy)diphenylsilane (28q)
A 25-mL, round-bottomed flask equipped with a magnetic stirrer bar was charged with
imidazole (309 mg, 4.50 mmol, 1.5 equiv) and trans-2-hexen-1-ol (313 mg, 371 µL, 3.00 mmol,
1.0 equiv) then was sealed with a rubber septum and purged with argon via an inlet needle.
CH2Cl2 (6.0 mL) was then added and stirring was commenced. tert-Butyldiphenylsilyl chloride
(922 mg, 872 µL, 3.30 mmol, 1.1 equiv) was added via syringe in one portion and the resultant
mixture was stirred under argon at rt for 16 h. The reaction mixture was then transferred to a
separatory funnel and diluted with CH2Cl2 (25-mL), washed sequentially with H2O (10 mL) and
brine (10 mL), then dried (MgSO4), filtered, and concentrated in vacuo (45 °C, ca. 5 mm Hg) to
give a colorless oil (1.17 g). Purification via flash column chromatography (40 g SiO2, 30 mm Ø,
wet loaded, 99:1 hexane/MTBE, ca. 5 mL fractions) gave 28q as a clear, colorless oil (900 mg,
89%, >99:1 dr, contaminated with ca. 4% regioisomeric alkene contaminants).
Data for 28q: 1H NMR: (500 MHz, CDCl3)
7.73–7.69 (m, 4 H, HC(2′,2′′)), 7.46–7.37 (m, 6 H, HC(3′,3′′,4′,4′′), 5.71–5.63 &
5.60–5.53 (m, 2 H, HC(2,3)), 4.23–4.14 (m, 2 H, HC(1)), 2.05–1.99 (m, 2 H,
HC(4)), 1.40 (sextet, J = 7.4 Hz, 2 H, HC(5)), 1.08 (s, 9 H, Sit-Bu), 0.92 (t, J = 7.4
Hz, 3 H, HC(6)). 13C NMR: (126 MHz, CDCl3)
135.5 (C(2′,2′′)), 133.9 (C(1′,1′′)), 131.2 (C(2)), 129.5 (C(4′,4′′)), 128.8 (C(3)),
127.6 (C(3′,3′′), 64.7 (C(1)), 34.3 (C(4)), 26.9 (SiCMe3), 22.4, (C(5)), 19.2
(SiCMe3), 13.7 (C(6))
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IR: (neat)
3071 (w), 3051 (w), 2956 (m), 2931 (m), 2895 (w), 2858 (m), 1591 (w), 1473 (w),
1462 (w), 1428 (m), 1379 (w), 1362 (w), 1112 (s), 1058 (m), 1009 (w), 969 (m),
823 (m), 739 (m), 701 (s)
MS: (EI+, TOF)
338.2 (M+, 29), 337.2 (13), 336.2 (14), 323.2 ([M-CH3]+, 18), 296.1 (17), 295.1
([M-CH3CH2CH2]+, 69), 282.1 ([M-CH3CH2CH2CH]+, 22), 281.1 (98), 203.1 (29),
200.1 (17), 199.1 (100), 197.1 (13), 183.0 (13), 181.0 (16)
TLC: Rf 0.38 (99:1 hexane/MTBE) [UV/KMnO4]
HRMS: (EI+, TOF)
calcd for C22H30OSi (M+): 338.2066, found: 338.2058
Preparation of (E)-tert-Butyldimethyl[(5-phenylpent-2-en-1-yl)oxy]silane (28s)
A 25-mL, round-bottomed flask equipped with a magnetic stirrer bar was charged with
(E)-5-phenylpent-2-en-1-ol 28u (487 mg, 3.00 mmol, 1.0 equiv) and imidazole (309 mg, 4.50
mmol, 1.5 equiv) then was sealed with a rubber septum and purged with argon via an inlet
needle. CH2Cl2 (6 mL) was then added and stirring was commenced. tert-Butyldimethylsilyl
chloride (497 mg, 3.30 mmol, 1.1 equiv) was added in one portion against a backflow of argon
and the resultant mixture was stirred at rt for 22 h. The reaction mixture was then transferred to a
separatory funnel and diluted with CH2Cl2 (25 mL), then was washed sequentially with H2O (10
mL) and brine (10 mL), then dried (MgSO4), filtered, and concentrated in vacuo (45 °C, ca. 5
mm Hg) to give a colorless oil (886 mg). Purification via flash column chromatography (40 g
SiO2, 30 mm Ø, wet loaded, 98:2 hexane/MTBE, ca. 5 mL fractions) gave a colorless oil (785
mg). Further purification via Kugelrohr distillation at reduced pressure (10–5 mm Hg) gave 28s
as a clear, colorless oil (758 mg, 91%, >99:1 dr). The 1H and 13C NMR spectroscopic data
matched that for alternative preparations.20
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Data for 28s: bp: 100 °C (ABT) (10–5 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.32–7.27 (m, 2 H, HC(2′)), 7.24–7.17 (m, 3 H, HC(3′,4′)), 5.71 (dt, J = 15.4, 6.5
Hz, 1 H, HC(2)), 5.64–5.56 (m, 1 H, HC(3)), 4.14 (d, J = 5.2 Hz, 1 H, HC(1)), 2.71
(t, J = 7.9 Hz, 2 H, HC(5)), 2.41–2.34 (m, 2 H, HC(4)), 0.93 (s, 9 H, Sit-Bu), 0.08 (s,
6 H, SiMe2) 13C NMR: (126 MHz, CDCl3)
δ 141.9 (C(1′)), 130.2 (C(2)), 129.8 (C(2′)), 128.4 & 128.2 (C(3,3′)), 125.7 (C(4′)),
63.9 (C(1)), 35.6 (C(5)), 34.0 (C(4)), 26.0 (SiCMe3), 18.4 (SiCMe3), –5.1 (SiMe2)
Preparation of (E)-4-(Benzyloxy)but-2-en-1-ol (28w)
Preparation of 4-(benzyloxy)but-2-yn-1-ol (S6). Following a literature procedure,20 an
oven-dried, 100-mL, round-bottomed flask equipped with a magnetic stirrer bar was charged
with 2-butyne-1,4-diol (3.47 g, 40.3 mmol, 4.0 equiv) and an aqueous solution (30 mL) of KOH
(2.26 g, 40.3 mmol, 4.0 equiv), then was sealed with a glass stopper and stirred at rt for 5 min.
Benzyl bromide (1.72 g, 1.2 mL, 10.0 mmol, 1.0 equiv) was added dropwise via syringe over 2–
3 min and the resultant mixture was allowed to stir at rt for 48 h. The reaction mixture was then
transferred to a separatory funnel and extracted with CH2Cl2 (3 × 30 mL), and the combined
organic extracts were washed with brine (20 mL), then dried (MgSO4), filtered, and concentrated
in vacuo (20–23 °C, ca. 20 mm Hg) to give a pale yellow oil. Purification via flash column
chromatography [40 g SiO2, 30 mm Ø, dry loaded, 95:5 → 90:10 → 80:20 → 70:30
hexane/EtOAc (100 mL, 100 mL, 300 mL, and 300 mL, respectively), ca. 20 mL fractions] gave
S6 as a colorless oil (1.56 g, 89%). The 1H NMR spectroscopic data matched that reported in the
literature.21
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Data for S6:
1H NMR: (400 MHz, CDCl3)
δ 7.38–7.28 (m, 5 H, HC(2′,3′,4′)), 4.60 (s, 2 H, HC(5′)), 4.32 (s, 2 H, HC(4)), 4.22
(t, J = 1.8 Hz, 2 H, HC(1)), 1.71 (br s, 1 H, OH) 13C NMR: (100 MHz, CDCl3)
δ 137.0 (C(1′)), 128.3 (C(3′)), 128.0 (C(2′)), 127.8 (C(4′)), 84.9 (C(3)), 81.1 (C(2)),
71.5 (C(5′)), 57.2 (C(4)), 50.6 (C(1))
Preparation of (E)-4-(benzyloxy)but-2-en-1-ol (28w). A flame-dried, 25-mL, round-
bottomed flask equipped with a magnetic stirrer bar was charged with 4-(benzyloxy)but-2-yn-1-
ol S6 (250 mg, 1.42 mmol, 1.0 equiv) then was sealed with a rubber septum and purged with
argon via an inlet needle. THF (7 mL) was added and the mixture was cooled in an ice-water
bath with stirring under argon. Red-Al® (≥60 wt% in toluene) (570 mg, 550 µL, 1.69 mmol, 1.2
equiv) was then added dropwise via syringe (resulting in gas evolution) and the resultant mixture
was stirred in the ice-water bath for 3 h. The reaction mixture was quenched with MeOH (0.3
mL) at 0 °C and the resultant turbid mixture was acidified with 2 M HCl at rt to pH 2, then was
transferred to a separatory funnel, diluted with H2O (20 mL), and extracted with EtOAc (3 × 20
mL). The combined organic extracts were washed with brine (20 mL), dried (MgSO4), filtered,
and concentrated in vacuo (20–23 °C, ca. 20 mm Hg) to give a pale yellow oil. Purification via
flash column chromatography [25 g SiO2, 24 mm Ø, dry loaded with 2 g SiO2, 90:10 → 80:20 →
65:35 hexane/EtOAc (100 mL, 200 mL, and 200 mL, respectively), ca. 10 mL fractions] gave
28w as a clear, pale yellow oil (204 mg, 81%). The 1H NMR spectroscopic data matched that for
alternative preparations.22
Data for 28w:
1H NMR: (400 MHz, CDCl3)
δ 7.45–7.26 (m, 5 H, HC(2′,3′,4′)), 5.97–5.81 (m, 2 H, HC(2,3)), 4.53 (s, 2 H,
HC(5′)), 4.20–4.15 (m, 2 H, HC(4)), 4.07–4.03 (m, 2 H, HC(1)), 1.50 (br s, 1 H,
OH) 13C NMR: (100 MHz, CDCl3)
δ 138.1 (C(1′)), 132.2 (C(3)), 128.4 (C(3′)), 127.8 & 127.7 (C(2′,4′)), 127.6 (C(2)),
72.3 & 70.0 (C(4,5’)), 63.0 (C(1))
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Preparation of Diaryl Diselenides
Preparation of Bis(4-methoxyphenyl) Diselenide (26)
A flame-dried, 100-mL, three-necked, round-bottomed flask equipped with a magnetic
stirrer bar, glass stopper, rubber septum, and an argon inlet was charged with 4-bromoanisole
(514 mg, 370 µL, 3.00 mmol, 1.0 equiv) and THF (15 mL), and stirring was commenced. The
mixture was cooled in a dry ice-acetone bath at –78 °C and tert-butyllithium (1.6 M in pentane,
3.9 mL, 6.24 mmol, 2.1 equiv) was then added dropwise via syringe over 5 min (N.B. the
solution turned yellow at each drop and quickly decolorized; it then remained yellow more than
halfway into the addition). The resultant mixture was stirred at –78 °C for 15 min then the dry-
ice acetone bath was replaced with an ice-water bath, and the reaction was stirred for a further 45
min. Selenium powder (261 mg, 3.30 mmol, 1.1 equiv) was added in one portion against a
backflow of argon, and the resultant mixture was allowed to stir in the ice-water bath for 15 min,
followed by a further 45 min at rt, to give a red-brown solution. The reaction mixture was
quenched with 1 M HCl (2 mL), then was transferred to a separatory funnel, diluted with H2O
(20 mL), and extracted with Et2O (3 × 20 mL). The combined organic extracts were washed with
brine (20 mL), dried (MgSO4), filtered, and concentrated in vacuo (20–23 °C, ca. 20 mm Hg) to
give an orange-brown oil (caution: stench!). The oil was dissolved in EtOH (10 mL), charged
with a NaOH pellet (ca. 60 mg), and the resultant mixture was vigorously stirred under
atmospheric air at rt for 2 h to give a deep orange solution. The solvent was then removed in
vacuo (45 °C, ca. 20 mm Hg) to give an orange paste. Purification via flash column
chromatography [45 g SiO2, 30 mm Ø, dry loaded with 2.5 g SiO2, 96:4 hexane/EtOAc (800 mL),
ca. 20 mL fractions] gave 26 as a clear, orange oil, which solidified to an orange solid on
standing in a –20 °C freezer for ca. 1 day (528 mg, 95%). Further purification was performed via
recrystallization from boiling 98:2 hexane/Et2O (8 mL), with gradual cooling to rt over 22 h in a
20 mL scintillation vial loosely sealed with a screw top cap. The crystals were collected via
filtration through filter paper in a Hirsch funnel under house vacuum, washed with (–78 °C)
pentane (5 × ca. 1 mL), crushed with a spatula, and dried in vacuo (0.05 mm Hg) overnight to
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give 26 as a yellow-orange, crystalline solid (458 mg, 87% mass return from the first crop). The 1H and 13C NMR spectroscopic data matched that for alternative preparations.23
Data for 26: mp: 51–53 °C (hexane/Et2O) [lit: 55–57 °C (MeOH)]24
1H NMR: (500 MHz, CDCl3)
δ 7.51 (d, J = 8.2 Hz, 4 H), 6.81 (d, J = 8.3 Hz, 4 H), 3.81 (s, 6 H) 13C NMR: (126 MHz, CDCl3)
δ 160.1, 135.45, 135.41, 135.36, 122.0, 114.7, 55.3
IR: (neat)
2931 (w), 2901 (w), 2834 (w), 1585 (m), 1570 (w), 1488 (s), 1460 (w), 1439 (w),
1287 (m), 1246 (s), 1171 (m), 1101 (w), 1070 (w), 1028 (m), 821 (m), 791 (w)
MS: (ESI+, TOF)
562.9 (17), 560.9 (40), 558.9 (49), 556.9 (37), 554.9 (21), 375.9 (12), 373.9 (M+,
36), 369.9 (19), 296.0 (20), 294.0 (100), 292.0 (52), 290.0 (18)
HRMS: (ESI+, TOF)
calcd for C14H14O2Se2 (M+): 373.9324, found: 373.9338
TLC: Rf 0.41 (92:8 hexane/EtOAc) [UV/KMnO4]
Preparation of Bis(2-methoxyphenyl) Diselenide (27)
A flame-dried, 100-mL, three-necked, round-bottomed flask equipped with a magnetic
stirrer bar, glass stopper, rubber septum, and an argon inlet was charged with 2-bromoanisole
(514 mg, 370 µL, 3.00 mmol, 1.0 equiv) and THF (15 mL), and stirring was commenced. The
mixture was cooled in a dry ice-acetone bath at –78 °C and tert-butyllithium (1.6 M in pentane,
3.9 mL, 6.24 mmol, 2.1 equiv) was then added dropwise via syringe over 5 min (N.B. the
solution turned yellow at each drop and quickly decolorized; it then remained yellow more than
halfway into the addition). The resultant mixture was stirred at –78 °C for 15 min then the dry-
ice acetone bath was replaced with an ice-water bath, and the reaction was stirred for a further 45
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min. Selenium powder (262 mg, 3.32 mmol, 1.1 equiv) was added in one portion against a
backflow of argon, and the resultant mixture was allowed to stir in the ice-water bath for 15 min,
followed by a further 45 min at rt, to give a red-brown solution. The reaction mixture was
quenched with 1 M HCl (2 mL), then was transferred to a separatory funnel, diluted with H2O
(20 mL), and extracted with Et2O (3 × 20 mL). The combined organic extracts were washed with
brine (20 mL), dried (MgSO4), filtered, and concentrated in vacuo (20–23 °C, ca. 20 mm Hg) to
give an orange-brown oil (caution: stench!). The oil was dissolved in EtOH (10 mL), charged
with a NaOH pellet (ca. 60 mg), and the resultant mixture was vigorously stirred under
atmospheric air at rt for 2 h to give a deep orange solution. The solvent was then removed in
vacuo (45 °C, ca. 20 mm Hg) to give an orange paste. Purification via flash column
chromatography [48 g SiO2, 30 mm Ø, dry loaded with 2.5 g SiO2, 96:4 hexane/EtOAc (800 mL),
ca. 20 mL fractions], followed by further purification of the mixed fractions [40 g SiO2, 30 mm
Ø, dry loaded with 2.2 g SiO2, 96:4 hexane/EtOAc (800 mL), ca. 10 mL fractions], gave 27 as a
yellow solid (487 mg, 87%). Further purification of an aliquot (310 mg) of this material was
performed via recrystallization from boiling 90:10 hexane/CH2Cl2 (6 mL), with gradual cooling
to rt over 22 h in a 20 mL scintillation vial loosely sealed with a screw top cap. The crystals were
collected via filtration through filter paper in a Hirsch funnel under house vacuum, washed with
(–78 °C) hexane (5 × ca. 1 mL), crushed with a spatula, and dried in vacuo (0.05 mm Hg)
overnight to give 27 as a bright yellow, crystalline solid (283 mg, 91% mass return from the first
crop). The 1H NMR spectroscopic data matched that for alternative preparations.25
Data for 27: mp: 85–86 °C (hexane/CH2Cl2) [lit: 79 °C (EtOH)]25
1H NMR: (500 MHz, CDCl3)
δ 7.56 (dd, J = 7.7, 1.5 Hz, 2 H), 7.21 (ddd, J = 8.1, 7.5, 1.6 Hz, 2 H), 6.88 (td, J =
7.6, 1.1 Hz, 2 H), 6.84–6.79 (m, 2 H), 3.91 (s, 6H) 13C NMR: (126 MHz, CDCl3)
δ 156.8, 130.6, 128.1, 121.9, 118.6, 110.1, 55.9
IR: (neat)
3004 (w), 2937 (w), 2834 (w), 1573 (m), 1470 (s), 1447 (w), 1432 (m), 1303 (w),
1268 (m), 1237 (s), 1182 (w), 1159 (w), 1125 (w), 1053 (m), 1022 (m), 788 (w),
751 (s), 711 (w), 655 (w)
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MS: (ESI+, TOF)
563.0 (34), 560.9 (85), 558.9 (100), 557.0 (79), 555.0 (45), 554.0 (18), 376.0 (13),
374.0 (M+, 41), 372.0 (37), 370.0 (21), 296.0 (11), 294.0 (54), 292.0 (27), 230.0
(18)
HRMS: (ESI+, TOF)
calcd for C14H14O2Se2 (M+): 373.9324, found: 373.9342
TLC: Rf 0.47 (92:8 hexane/EtOAc) [UV/KMnO4]
General Procedure I: Reaction Development with Cyclohexene (Table 1)
An oven-dried, 4-mL dram vial equipped with a magnetic stirrer bar was taken into the
glovebox and charged sequentially with diphenyl diselenide (PhSeSePh) (3.1 mg, 0.01 mmol, 5
mol %), the requisite tetraalkylammonium chloride (n-Bu4NCl or BnEt3NCl) (0.0–3.0 equiv),
and the requisite oxidant (N-fluoropyridinium tetrafluoroborate 11 or Selectfluor® 12) (0.26
mmol, 1.3 equiv), and was then sealed with a rubber septum, removed from the box, and placed
under argon via an inlet needle. MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL,
0.20 mmol, 1.0 equiv), and chlorotrimethylsilane (Me3SiCl) (0.0–3.0 equiv) were then added
sequentially via syringe, and stirring was commenced. After ca. 10 min, cyclohexene 6 (16.4 mg,
20.3 µL, 0.20 mmol, 1.0 equiv) was added via syringe, and the resultant suspension was stirred at
rt for ca. 20 h. The reaction mixture was then passed through a short plug of Celite (ca. 1 cm
depth in a Pasteur pipet) and the filtrate was analyzed by 1H NMR spectroscopy in order to
assess the product distribution and determine the syn/anti diastereoisomeric ratio (dr). NMR
yields were measured against 1,1,2,2-tetrachloroethane (1.0 equiv) as an internal standard using
diagnostic 1H NMR resonances measured for authentic samples of compounds 7–10 (and the
anti-diastereoisomer of 7) in MeCN-d3.
Data for 7: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 4.41–4.37 (m, 2 H, HC(1,2))
Data for the anti-diastereoisomer of 7: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 4.04–3.98 (m, 2 H, HC(1,2))
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Data for 8: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only) δ 5.86–5.81 (m, 1 H, HC(3)), 5.76–5.72 (m, 1 H, HC(2))
Data for 9: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only) δ 4.18–4.10 (m, 1 H, HC(2)), 3.50–3.42 (m, 1 H, HC(1))
Data for 10: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only) δ 4.93 & 4.78 (ddd, J = 12.1, 10.7, 3.8 Hz, 1 H, ddd, J = 11.8, 10.8, 4.4 Hz, 1 H,
HC(1,2))
Reaction Development with Cyclohexene (Table 1)
Table 1 Entry 1
Following General Procedure I, PhSeSePh (3.1 mg, 0.01 mmol, 5 mol %), n-Bu4NCl
(167 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), and cyclohexene 6 (16.4 mg,
20 µL, 0.20 mmol, 1.0 equiv) were reacted to give: 6 (50%), 7 (19%, >99:1 dr), 8 (3%) and 9
(9%).
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Table 1 Entry 2
Following General Procedure I, PhSeSePh (3.1 mg, 0.01 mmol, 5 mol %), n-Bu4NCl
(167 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (21.7 mg, 25.4 µL,
0.20 mmol, 1.0 equiv), and cyclohexene 6 (16.4 mg, 20 µL, 0.20 mmol, 1.0 equiv) were reacted
to give: 6 (12%), 7 (61%, >99:1 dr), 8 (10%), and 9 (10%).
Table 1 Entry 3
Following General Procedure I, PhSeSePh (3.1 mg, 0.01 mmol, 5 mol %), n-Bu4NCl
(167 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (43.4 mg, 50.8 µL,
0.40 mmol, 2.0 equiv), and cyclohexene 6 (16.4 mg, 20 µL, 0.20 mmol, 1.0 equiv) were reacted
to give: 7 (81%, >99:1 dr) and 8 (10%).
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Table 1 Entry 4
Following General Procedure I, PhSeSePh (3.1 mg, 0.01 mmol, 5 mol %), n-Bu4NCl
(167 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (65.1 mg, 76.2 µL,
0.60 mmol, 3.0 equiv), and cyclohexene 6 (16.4 mg, 20 µL, 0.20 mmol, 1.0 equiv) were reacted
to give: 7 (81%, >99:1 dr) and 8 (8%).
Table 1 Entry 5
Following General Procedure I, PhSeSePh (3.1 mg, 0.01 mmol, 5 mol %), n-Bu4NCl
(139 mg, 0.50 mmol, 2.5 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (43.4 mg, 50.8 µL,
0.40 mmol, 2.0 equiv), and cyclohexene 6 (16.4 mg, 20 µL, 0.20 mmol, 1.0 equiv) were reacted
to give: 7 (74%, >99:1 dr) and 8 (10%).
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Table 1 Entry 6
Following General Procedure I, PhSeSePh (3.1 mg, 0.01 mmol, 5 mol %), 11 (48.0 mg,
0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20
mmol, 1.0 equiv), Me3SiCl (43.4 mg, 50.8 µL, 0.40 mmol, 2.0 equiv), and cyclohexene 6 (16.4
mg, 20 µL, 0.20 mmol, 1.0 equiv) were reacted to give: 6 (54%), 8 (2%), 10 (8%), and an
unidentified species (11%).
Table 1 Entry 7
Following General Procedure I, PhSeSePh (3.1 mg, 0.01 mmol, 5 mol %), n-Bu4NCl
(167 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), CD2Cl2 (1.0 mL), 1,1,2,2-
tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (43.4 mg, 50.8 µL, 0.40
mmol, 2.0 equiv), and cyclohexene 6 (16.4 mg, 20 µL, 0.20 mmol, 1.0 equiv) were reacted to
give: 7 (73%, >99:1 dr), 8 (12%) and 9 (4%).
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Table 1 Entry 8
Following General Procedure I, PhSeSePh (3.1 mg, 0.01 mmol, 5 mol %), n-Bu4NCl
(167 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), THF-d8 (1.0 mL), 1,1,2,2-
tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (43.4 mg, 50.8 µL, 0.40
mmol, 2.0 equiv), and cyclohexene 6 (16.4 mg, 20 µL, 0.20 mmol, 1.0 equiv) were reacted to
give: 6 (55%), 7 (17%, >99:1 dr), and 8 (2%).
Table 1 Entry 9
Following General Procedure I, PhSeSePh (3.1 mg, 0.01 mmol, 5 mol %), n-Bu4NCl
(167 mg, 0.60 mmol, 3.0 equiv), 12 (97.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (43.4 mg, 50.8 µL,
0.40 mmol, 2.0 equiv), and cyclohexene 6 (16.4 mg, 20 µL, 0.20 mmol, 1.0 equiv) were reacted
to give: 7 (71%, >99:1 dr) and 8 (10%).
Table 1 Entry 10
Following General Procedure I, PhSeSePh (3.1 mg, 0.01 mmol, 5 mol %), BnEt3NCl
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(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (43.4 mg, 50.8 µL,
0.40 mmol, 2.0 equiv), and cyclohexene 6 (16.4 mg, 20 µL, 0.20 mmol, 1.0 equiv) were reacted
to give: 7 (83%, >99:1 dr) and 8 (10%).
Background Reaction (Omission of PhSeSePh)
Following General Procedure I (but with omission of PhSeSePh), BnEt3NCl (138 mg,
0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL), 1,1,2,2-
tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (43.7 mg, 51 µL, 0.40 mmol,
2.0 equiv), and cyclohexene 6 (16.4 mg, 20 µL, 0.20 mmol, 1.0 equiv) were reacted to give: 6
(42%), anti-7 (~35%; diagnostic signal was overlapped with that from an unidentified species at
ca. δ 3.99–3.94), and 8 (16%).
General Procedure II: Survey of Lewis Base Additives with (E)-1-Benzyloxyl-4-hexene (17)
(Table 2, Entries 1-8)
An oven-dried, 4-mL dram vial equipped with a magnetic stirrer bar was taken into the
glovebox and charged sequentially with diphenyl diselenide (PhSeSePh) (3.4 mg, 0.01 mmol, 5
mol %), benzyltriethylammonium chloride (BnEt3NCl) (138 mg, 0.60 mmol, 3.0 equiv), and N-
fluoropyridinium tetrafluoroborate 11 (48.0 mg, 0.26 mmol, 1.3 equiv). In the case of solid
Lewis base additives (entries 6 and 7), the requisite additive was also added at this point. The
vial was then sealed with a rubber septum, removed from the box, and placed under argon via an
inlet needle. MeCN-d3 (1.0 mL) and 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0
equiv) were then added sequentially via syringe. In the case of liquid Lewis base additives
(entries 3–5 and 8), the requisite additive was also added at this point via syringe. Finally,
chlorotrimethylsilane (Me3SiCl) (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv) was added via syringe
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and stirring was commenced. After ca. 10 min, (E)-1-benzyloxyl-4-hexene 17 (38.1 mg, 39 µL,
0.20 mmol, 1.0 equiv) was added via syringe, then the argon inlet needle was removed and the
resultant suspension was stirred at rt. Once the reaction mixture had become homogeneous, it
was stirred for a further ca. 15 min and an aliquot (0.5 mL) was transferred via syringe into an
oven-dried NMR tube. The reaction mixture was then analyzed by 1H NMR spectroscopy in
order to assess the ratio of product 18 to by-products 19–22, and to determine the syn/anti
diastereoisomeric ratio (dr) for 18 (by comparison to an authentic sample of the anti-
diastereoisomer of 18). Relative ratios were determined using diagnostic 1H NMR resonances for
product 18 and by-products 19–22.
Data for 18: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 4.35 (qd, J = 6.6, 2.7 Hz, 1 H, HC(5)), 4.16 (ddd, J = 9.4, 4.1, 2.7 Hz, 1 H,
HC(4))
Data for the anti-diastereoisomer of 18: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 4.29 (qd, J = 6.6, 4.8 Hz, 1 H, HC(5)), 4.14 (ddd, J = 9.6, 4.8, 3.1 Hz, 1 H,
HC(4))
Data for (19–22): 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 5.89 (ddd, J = 17.0, 10.2, 8.3 Hz, 1 H, HC(5) for 21), 5.78–5.71 & 5.68–5.62 (m,
2 H, HC(3,4) for 22), 5.69–5.62 (m, 1 H, HC(5) for 19), 5.57 (tq, J = 7.8, 1.2 Hz, 1
H, HC(4) for 20), 5.26 (dt, J = 16.9, 1.1 Hz, 1 H, HC(6) for 21), 5.12 (dt, J = 10.2,
0.9 Hz, 1 H, HC(6) for 21)
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Survey of Lewis Base Additives (Table 2)
Table 2 Entry 1
Following General Procedure II, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL,
0.41 mmol, 2.0 equiv), and alkene 17 (38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv) were reacted for 6
h to give complete conversion of 17 to a 80:20 mixture of 18 (99:1 dr):(19–22).
Table 2 Entry 2
Following General Procedure II, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (0.75 mL),
sulfolane (0.25 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl
(44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene 17 (38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv)
were reacted for 2 h to give complete conversion of 17 to a 80:20 mixture of 18 (99:1 dr):(19–
22).
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Table 2 Entry 3
Following General Procedure II, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), hexamethylphosphoramide
(HMPA) (36.0 mg, 35 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41 mmol, 2.0
equiv), and alkene 17 (38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv) were reacted for 3 h to give
complete conversion of 17 to a 82:18 mixture of 18 (98:2 dr):(19–22).
Table 2 Entry 4
Following General Procedure II, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), N,N′-dimethylpropyleneurea
(DMPU) (25.4 mg, 24 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41 mmol, 2.0
equiv), and alkene 17 (38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv) were reacted for 3.5 h to give
complete conversion of 17 to a 80:20 mixture of 18 (98:2 dr):(19–22).
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Table 2 Entry 5
Following General Procedure II, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), N,N′-dimethyl-2-
imidazolidinone (DMI) (23.2 mg, 22 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41
mmol, 2.0 equiv), and alkene 17 (38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv) were reacted for 2.5 h
to give complete conversion of 17 to a 80:20 mixture of 18 (99:1 dr):(19–22).
Table 2 Entry 6
Following General Procedure II, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), triphenylphosphine oxide
(35.7 mg, 0.20 mmol, 1.0 equiv), MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL,
0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene 17 (38.1 mg,
39 µL, 0.20 mmol, 1.0 equiv) were reacted for 3.5 h to give complete conversion of 17 to a 80:20
mixture of 18 (98:2 dr):(19–22).
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Table 2 Entry 7
Following General Procedure II, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), pyridine N-oxide (19.0 mg,
0.20 mmol, 1.0 equiv), MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20
mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene 17 (38.1 mg, 39
µL, 0.20 mmol, 1.0 equiv) were reacted for 2.5 h to give complete conversion of 17 to a 80:20
mixture of 18 (98:2 dr):(19–22).
Table 2 Entry 8
Following General Procedure II, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), 2,6-lutidine N-oxide (25.2 mg,
23 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene 17
(38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv) were reacted for 2 h to give complete conversion of 17
to a 80:20 mixture of 18 (99:1 dr):(19–22).
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General Procedure III: Survey of Diaryl Diselenides with (E)-1-Benzyloxyl-4-hexene (17)
(Table 2, Entries 9–12)
An oven-dried, 4-mL dram vial equipped with a magnetic stirrer bar was taken into the
glovebox and charged sequentially with the requisite diaryl diselenide [(ArylSe)2] (0.01 mmol, 5
mol %), benzyltriethylammonium chloride (BnEt3NCl) (138 mg, 0.60 mmol, 3.0 equiv), and N-
fluoropyridinium tetrafluoroborate 11 (48.0 mg, 0.26 mmol, 1.3 equiv), and was then sealed with
a rubber septum, removed from the box, and placed under argon via an inlet needle. MeCN-d3
(1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), and
chlorotrimethylsilane (Me3SiCl) (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv) were then added
sequentially via syringe and stirring was commenced. After ca. 10 min, (E)-1-benzyloxyl-4-
hexene 17 (38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv) was added via syringe, then the argon inlet
needle was removed and the resultant suspension was stirred at rt. Once the reaction mixture had
become homogeneous, it was stirred for a further ca. 15 min and an aliquot (0.5 mL) was
transferred via syringe into an oven-dried NMR tube. The reaction mixture was then analyzed by 1H NMR spectroscopy in order to assess the ratio of product 18 to by-products 19–22, and to
determine the syn/anti diastereoisomeric ratio (dr) for 18 (by comparison to an authentic sample
of the anti-diastereoisomer of 18). Relative ratios were determined using diagnostic 1H NMR
resonances for product 18 and by-products 19–22.
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Survey of Diaryl Diselenides (Table 2)
Table 2 Entry 9
Following General Procedure III, bis[3,5-bis(trifluoromethyl)phenyl] diselenide 24 (5.8
mg, 0.01 mmol, 5 mol %), BnEt3NCl (138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol,
1.3 equiv), MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv),
Me3SiCl (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene 17 (38.1 mg, 39 µL, 0.20 mmol, 1.0
equiv) were reacted for 10 h to give complete conversion of 17 to a 58:42 mixture of 18 (88:12
dr):(19–22).
Table 2 Entry 10
Following General Procedure III, bis(2-nitrophenyl) diselenide 25 (4.0 mg, 0.01 mmol, 5
mol %), BnEt3NCl (138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-
d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2
mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene 17 (38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv) were
reacted for 18 h to give complete conversion of 17 to a 59:41 mixture of 18 (55:45 dr):(19–22).
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Table 2 Entry 11
Following General Procedure III, bis(4-methoxyphenyl) diselenide 26 (3.7 mg, 0.01
mmol, 5 mol %), BnEt3NCl (138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv),
MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl
(44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene 17 (38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv)
were reacted for 3.5 h to give complete conversion of 17 to a 90:10 mixture of 18 (99:1 dr):(19–
22).
Table 2 Entry 12
Following General Procedure III, bis(2-methoxyphenyl) diselenide 27 (3.7 mg, 0.01
mmol, 5 mol %), BnEt3NCl (138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv),
MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl
(44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene 17 (38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv)
were reacted for 8 h to give complete conversion of 17 to a 83:17 mixture of 18 (98:2 dr):(19–
22).
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Table S1. Preliminary Survey of Reaction Generality
entry substrate A
PhSeSePh (5 mol %)
B PhSeSePh (5 mol %)
& 23 (1.0 equiv)
C 26
(5 mol %)
1
19 h (83%) >99:1 dr
89:11
8 h (73%) >99:1 dr 98.5:1.5
10 h (73%) >99:1 dr
96:4
2
7 h (61%) 97:3 dr 80:20
4 h (81%) >98:2 dr
88:12
6 h (83%) >97:3 dr
92:8
3
6 h (79%) 99:1 dr 82:18
3 h (79%) >99:1 dr
94:6
3.5 h (74%) >98:2 dr
85:15
4
14 h (91%) >99:1 dr
n.d.a
9 h (66%) 99:1 dr
n.d.a
12 h (65%) >98:2 dr
93:7
5
7 h (64%) >99:1 dr
78:22
5 h (77%) 99:1
81:19
–b
6
5 h (91%) 90:10
3 h (90%) 90:10
–b
7
6 h (73%) 99:1 dr 80:20
2 h (79%) 99:1 dr 80:20
5 hc (71%) 99:1 dr 85:15
NMR yields, given in parentheses, were measured against 1,1,2,2-tetrachloroethane (1.0 equiv) as an internal standard. In all cases ≥93% of the alkene starting material was consumed. The ratios of product to by-products in the crude reaction mixtures are given in italics. a Ratio of product to by-products could not be determined (n.d.) via 1H NMR spectroscopy. b Pre-catalyst 26 was not surveyed in the catalytic syn-dichlorination of alkenes 28r and 28d. c 2,6-Lutidine N-oxide 23 (1.0 equiv) was added to the reaction mixture with pre-catalyst 26 in the catalytic syn-dichlorination of alkene 17.
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General Procedure IV: Preliminary Survey of Reaction Generality (Table S1)
An oven-dried, 4-mL dram vial equipped with a magnetic stirrer bar was taken into the
glovebox and charged sequentially with the requisite diaryl diselenide [(ArylSe)2] (0.01 mmol, 5
mol %), benzyltriethylammonium chloride (BnEt3NCl) (138 mg, 0.60 mmol, 3.0 equiv), and N-
fluoropyridinium tetrafluoroborate 11 (48.0 mg, 0.26 mmol, 1.3 equiv), and was then sealed with
a rubber septum, removed from the box, and placed under argon via an inlet needle. MeCN-d3
(1.0 mL) and 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv) were then added
and stirring was commenced. 2,6-Lutidine N-oxide 23 (25.2 mg, 23 µL, 0.20 mmol, 1.0 equiv)
was added (for condition B, entries 1–7, and condition C, entry 7), followed by
chlorotrimethylsilane (Me3SiCl) (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), both via syringe. After
ca. 10 min, the alkene substrate (0.20 mmol) was transferred via syringe to the reaction mixture
[for alkenes of unknown density, only 0.6 mL of MeCN-d3 was added initially and the remaining
0.4 mL (in two 0.2 mL portions) was used to transfer the alkene across from an oven-dried, 4 mL
dram vial under an argon atmosphere, via syringe]. The argon inlet needle was then removed, the
rubber septum sealed, and the resultant suspension was stirred at rt. At the time stated, an aliquot
(0.5 mL) was transferred via syringe into an oven-dried NMR tube, and the reaction was
analyzed by 1H NMR spectroscopy to measure the NMR yield, syn/anti diastereoisomeric ratio
(dr) and product to by-products ratio via diagnostic 1H NMR resonances (in the range δ 5.9–4.0).
Table S1 Condition A Entry 1
Following General Procedure IV, PhSeSePh (3.1 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL,
0.41 mmol, 2.0 equiv), and cyclohexene 6 (16.4 mg, 20 µL, 0.20 mmol, 1.0 equiv) were reacted
for 19 h to give complete conversion to a 89:11 mixture of 7 (83% NMR yield, >99:1 dr):8.
(Note: see General Procedure I for diagnostic 1H NMR resonances for 7 and 8).
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Table S1 Condition B Entry 1
Following General Procedure IV, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), 2,6-lutidine N-oxide 23 (25.2
mg, 23 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and
cyclohexene 6 (16.4 mg, 20 µL, 0.20 mmol, 1.0 equiv) were reacted for 8 h to give 96%
conversion to a 98.5:1.5 mixture of 7 (73% NMR yield, >99:1 dr):8. (Note: see General
Procedure I for diagnostic 1H NMR resonances for 7 and 8).
Table S1 Condition C Entry 1
Following General Procedure IV, bis(4-methoxyphenyl) diselenide 26 (3.7 mg, 0.01
mmol, 5 mol %), BnEt3NCl (138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv),
MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl
(44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and cyclohexene 6 (16.4 mg, 20 µL, 0.20 mmol, 1.0
equiv) were reacted for 8 h to give 95% conversion to a 96:4 mixture of 7 (73% NMR yield,
>99:1 dr):8. (Note: see General Procedure I for diagnostic 1H NMR resonances for 7 and 8).
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Table S1 Condition A Entry 2
Following General Procedure IV, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL,
0.41 mmol, 2.0 equiv), and alkene 28q (67.7 mg, 0.20 mmol, 1.0 equiv) were reacted for 7 h to
give complete conversion to a 80:20 mixture of 29q (61% NMR yield, 97:3 dr):(S7–S9). [Note:
the diagnostic 1H NMR chemical shifts for (S7 + S8 + S9) were tentatively assigned].
Data for 29q: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 4.51 (ddd, J = 8.2, 5.4, 2.2 Hz, 1 H, HC(3)), 4.25 (ddd, J = 7.9, 5.9, 2.2 Hz, 1 H,
HC(2))
Data for the anti-diastereoisomer of 29q: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 4.37 (ddd, J = 9.5, 6.3, 2.8 Hz, 1 H, HC(3)), 4.22 (dt, J = 6.4, 4.8 Hz, 1 H, HC(2))
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Data for (S7–S9): 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 5.87–5.78, 5.69–5.62, 5.57–5.46 (m, 1 H for S7, 1 H for S8, 2 H for S9, HC(3) for
S7, HC(2) for S8, HC(3,4) for S9)
Table S1 Condition B Entry 2
Following General Procedure IV, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), 2,6-lutidine N-oxide 23 (25.2
mg, 23 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene
28q (67.7 mg, 0.20 mmol, 1.0 equiv) were reacted for 4 h to give complete conversion to a 88:12
mixture of 29q (81% NMR yield, >98:2 dr):(S7–S9). The by-product giving rise to the 1H signal
at δ 5.69–5.62 was only present in a trace amount. [Note: the diagnostic 1H NMR chemical shifts
for (S7–S9) were tentatively assigned].
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Table S1 Condition C Entry 2
Following General Procedure IV, bis(4-methoxyphenyl) diselenide 26 (3.7 mg, 0.01
mmol, 5 mol %), BnEt3NCl (138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv),
MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl
(44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene 28q (67.7 mg, 0.20 mmol, 1.0 equiv) were
reacted for 6 h to give complete conversion to a 92:8 mixture of 29q (83% NMR yield, >97:3
dr):(S7–S9). The by-product giving rise to the 1H signal at δ 5.69–5.62 was absent. [Note: the
diagnostic 1H NMR chemical shifts for (S7–S9) were tentatively assigned].
Table S1 Condition A Entry 3
Following General Procedure IV, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
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1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL,
0.41 mmol, 2.0 equiv), and alkene 28h (38.1 mg, 0.20 mmol, 1.0 equiv) were reacted for 6 h to
give complete conversion to a 82:18 mixture of 29h (79% NMR yield, 99:1 dr):(S10 + S11 + 21
+ 22). S10 and S11 were the major by-products observed.
Data for 29h: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 4.29 (qd, J = 6.6, 4.8 Hz, 1 H, HC(5)), 4.14 (ddd, J = 9.6, 4.8, 3.1 Hz, 1 H,
HC(4))
Data for the anti-diastereoisomer of 29h: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 4.35 (qd, J = 6.6, 2.7 Hz, 1 H, HC(5)), 4.16 (ddd, J = 9.4, 4.1, 2.7 Hz, 1 H,
HC(4))
Data for (S10 + S11 + 21 + 22): 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 5.88 (ddd, J = 16.9, 10.2, 8.2 Hz, 1 H, HC(5) for 21), 5.77–5.70 & 5.68–5.62 (m,
2 H, HC(3,4) for 22), 5.59–5.50 (m, 1 H for S10, 1 H for S11, HC(5) for S10,
HC(4) for S11), 5.25 (dt, J = 17.0, 1.2 Hz, 1 H, HC(6) for 21), 5.13–5.09 (m, 1 H,
HC(6) for 21)
Table S1 Condition B Entry 3
Following General Procedure IV, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
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1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), 2,6-lutidine N-oxide 23 (25.2
mg, 23 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene
28h (38.1 mg, 0.20 mmol, 1.0 equiv) were reacted for 3 h to give complete conversion to a 94:6
mixture of 29h (79% NMR yield, >99:1 dr):(S10 + S11 + 21 + 22). S10 and S11 were the major
by-products observed, while 21 and 22 were only present in trace amounts under these
conditions.
Table S1 Condition C Entry 3
Following General Procedure IV, bis(4-methoxyphenyl) diselenide 26 (3.7 mg, 0.01
mmol, 5 mol %), BnEt3NCl (138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv),
MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl
(44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene 28h (38.1 mg, 0.20 mmol, 1.0 equiv) were
reacted for 3.5 h to give complete conversion to a 85:15 mixture of 29h (74% NMR yield, >98:2
dr):(S10 + S11 + 21 + 22). S10 and S11 were the major by-products observed.
Table S1 Condition A Entry 4
Following General Procedure IV, PhSeSePh (3.1 mg, 0.01 mmol, 5 mol %), BnEt3NCl
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(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL,
0.41 mmol, 2.0 equiv), and alkene 28t (20.0 mg, 24 µL, 0.20 mmol, 1.0 equiv) were reacted for
14 h to give complete conversion to a mixture of 29t (91% NMR yield, >99:1 dr), S12, S13, and
S14. Unfortunately the ratio 29t:(S12–S14) could not be determined due to signal overlap.
Data for 29t: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 4.48–4.43 (m, 1 H, HC(3)), 4.29 (ddd, J = 7.9, 6.0, 2.1 Hz, 1 H, HC(2))
Data for the anti-diastereoisomer of 29t: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 4.25–4.20 (m, 2 H, HC(2,3))
Table S1 Condition B Entry 4
Following General Procedure IV, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), 2,6-lutidine N-oxide 23 (25.2
mg, 23 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene
28t (20.0 mg, 24 µL, 0.20 mmol, 1.0 equiv) were reacted for 9 h to give ~93% conversion to a
mixture of 29t (66% NMR yield, 99:1 dr), S12, S13, and S14. Unfortunately the ratio 29t:(S12–
S14) could not be determined due to signal overlap from unidentified background reactions.
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Table S1 Condition C Entry 4
Following General Procedure IV, bis(4-methoxyphenyl) diselenide 26 (3.7 mg, 0.01
mmol, 5 mol %), BnEt3NCl (138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv),
MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl
(44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene 28t (20.0 mg, 24 µL, 0.20 mmol, 1.0 equiv)
were reacted for 12 h to give ~96% conversion to a 93:7 mixture of 29t (65% NMR yield, >98:2
dr):( S12–S14). [Note: the diagnostic 1H NMR chemical shifts for (S12–S14) were tentatively
assigned].
Data for (S12–S14): 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 5.84–5.76, 5.66–5.56, 5.53–5.47 (m, 1 H for S12, 1 H for S13, 2 H for S14,
HC(3) for S12, HC(2) for S13, HC(3,4) for S14)
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Table S1 Condition A Entry 5
Following General Procedure IV, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL,
0.41 mmol, 2.0 equiv), and alkene 28r (67.7 mg, 0.20 mmol, 1.0 equiv) were reacted for 7 h to
give complete conversion to a 78:22 mixture of 29r (64% NMR yield, >99:1 dr):(S15 + S16 +
S9). [Note: the diagnostic 1H NMR chemical shifts for (S15 + S16 + S9) were tentatively
assigned].
Data for 29r: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 4.37 (ddd, J = 9.5, 6.3, 2.8 Hz, 1 H, HC(3)), 4.22 (dt, J = 6.4, 4.8 Hz, 1 H, HC(2))
Data for the anti-diastereoisomer of 29r: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 4.51 (ddd, J = 8.2, 5.4, 2.2 Hz, 1 H, HC(3)), 4.25 (ddd, J = 7.9, 5.9, 2.2 Hz, 1 H,
HC(2))
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Data for (S15 + S16 + S9): 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 5.8–5.81, 5.78–5.70, 5.63–5.54 (m, 1 H for S15, 1 H for S16, 2 H for S9, HC(3)
for S15, HC(2) for S16, HC(3,4) for S9)
Table S1 Condition B Entry 5
Following General Procedure IV, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), 2,6-lutidine N-oxide 23 (25.2
mg, 23 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene
28r (67.7 mg, 0.20 mmol, 1.0 equiv) were reacted for 5 h to give complete conversion to a 81:19
mixture of 29r (77% NMR yield, 99:1 dr):(S15 + S16 + S9). [Note: the diagnostic 1H NMR
chemical shifts for (S15 + S16 + S9) were tentatively assigned].
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Table S1 Condition A Entry 6
Following General Procedure IV, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL,
0.41 mmol, 2.0 equiv), and alkene 28d (62.1 mg, 0.20 mmol, 1.0 equiv) were reacted for 5 h to
give complete conversion to a 90:10 mixture of 29d (91% NMR yield):(S17–S19). [Note: the
diagnostic 1H NMR chemical shifts for (S17–S19) were tentatively assigned].
Data for 29d: 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 4.45 (dtd, J = 9.3, 5.5, 3.6 Hz, 1 H, HC(3))
Data for (S17–S19): 1H NMR: (500 MHz, MeCN-d3, diagnostic resonances only)
δ 6.18–6.16 (m, 1 H, HC(4) for S17), 6.12–6.08 (m, 1 H, HC(3) for S17), 5.95–5.86
(m, 2 H, HC(2,3) for S19), 5.03 (dq, J = 17.2, 1.7 Hz, 1 H, HC(4) for S18), 4.98
(ddt, J = 10.3, 2.3, 1.1 Hz, 1 H, HC(4) for S18)
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Table S1 Condition B Entry 6
Following General Procedure IV, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL),
1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), 2,6-lutidine N-oxide 23 (25.2
mg, 23 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene
28d (62.1 mg, 0.20 mmol, 1.0 equiv) were reacted for 3 h to give >95% conversion to a 90:10
mixture of 29d (90% NMR yield):(S17–S19). [Note: the diagnostic 1H NMR chemical shifts for
(S17–S19) were tentatively assigned].
Table S1 Condition C Entry 7
Following General Procedure IV, bis(4-methoxyphenyl) diselenide 26 (3.7 mg, 0.01
mmol, 5 mol %), BnEt3NCl (138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg, 0.26 mmol, 1.3 equiv),
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MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), 2,6-
lutidine N-oxide 23 (25.2 mg, 23 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41
mmol, 2.0 equiv), and alkene 17 (38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv) were reacted for 18 h to
give ~99% conversion to a 85:15 mixture of 18 (72% NMR yield, 99:1 dr):(19–22). Earlier time
points taken at 3 h and 5 h showed 61% and 71% NMR yields of 18, respectively, with the same
85:15 ratio of 18:(19–22) in both cases.
General Procedure V: Control Experiments with (E)-1-Benzyloxyl-4-hexene (17)
[Note: Reagents were selectively omitted from the following procedure as described in
the various control experiments below]. An oven-dried, 4-mL dram vial equipped with a
magnetic stirrer bar was taken into the glovebox and charged sequentially with diphenyl
diselenide (PhSeSePh) (3.4 mg, 0.01 mmol, 5 mol %), benzyltriethylammonium chloride
(BnEt3NCl) (138 mg, 0.60 mmol, 3.0 equiv), and N-fluoropyridinium tetrafluoroborate 11 (48.0
mg, 0.26 mmol, 1.3 equiv), and was then sealed with a rubber septum, removed from the box,
and placed under argon via an inlet needle. MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3
mg, 21 µL, 0.20 mmol, 1.0 equiv), 2,6-lutidine N-oxide 23 (25.2 mg, 23 µL, 0.20 mmol, 1.0
equiv), and chlorotrimethylsilane (Me3SiCl) (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv) were then
added sequentially and stirring was commenced. After ca. 10 min, (E)-1-benzyloxyl-4-hexene 17
(38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv) was transferred via syringe to the reaction mixture. The
argon inlet needle was then removed, the rubber septum sealed, and the resultant suspension was
stirred at rt. At the time stated, an aliquot (0.1 mL) was transferred via syringe into an oven-dried
NMR tube and was diluted with MeCN-d3 (0.4 mL), then the reaction was analyzed by 1H NMR
spectroscopy.
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Control Experiment I – Omission of PhSeSePh
Following General Procedure V, BnEt3NCl (138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg,
0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20
mmol, 1.0 equiv), 23 (25.2 mg, 23 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41
mmol, 2.0 equiv), and alkene 17 (38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv) were reacted. After 20
h, 50% conversion of 17 had occurred to give the anti-diastereomer of 29h (40% NMR yield)
and allylic chloride 21 (6% NMR yield) as the main by-product (based on the diagnostic 1H
NMR resonance for 21 described in General Procedure II). After 40 h, 86% conversion of 17 had
occurred to give the anti-diastereoisomer of 29h (60% NMR yield) and 21 (8% NMR yield).
Control Experiment II – Omission of PhSeSePh and 2,6-Lutidine N-Oxide 23
Following General Procedure V, BnEt3NCl (138 mg, 0.60 mmol, 3.0 equiv), 11 (48.0 mg,
0.26 mmol, 1.3 equiv), MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL, 0.20
mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL, 0.41 mmol, 2.0 equiv), and alkene 17 (38.1 mg, 39
µL, 0.20 mmol, 1.0 equiv) were reacted. After 20 h, 46% conversion of 17 had occurred to give
the anti-diastereoisomer of 29h (38% NMR yield) and allylic chloride 21 (7% NMR yield) as the
main by-product (based on the diagnostic 1H NMR resonance for 21 described in General
Procedure II). After 40 h, complete conversion of 17 had occurred to give the anti-
diastereoisomer of 29h (74% NMR yield) and 21 (10% NMR yield).
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Control Experiment III – Omission of N-Fluoropyridinium Tetrafluoroborate 11
Following General Procedure V, PhSeSePh (3.4 mg, 0.01 mmol, 5 mol %), BnEt3NCl
(138 mg, 0.60 mmol, 3.0 equiv), MeCN-d3 (1.0 mL), 1,1,2,2-tetrachloroethane (33.3 mg, 21 µL,
0.20 mmol, 1.0 equiv), 23 (25.2 mg, 23 µL, 0.20 mmol, 1.0 equiv), Me3SiCl (44.2 mg, 52 µL,
0.41 mmol, 2.0 equiv), and alkene 17 (38.1 mg, 39 µL, 0.20 mmol, 1.0 equiv) were reacted.
After either 20 h or 40 h, no conversion of 17 had occurred.
General Procedure VI: NMR Spectroscopic Studies on Catalytic, syn-Dichlorination of
Volatile Alkenes
An oven-dried, 10-mL Schlenk flask equipped with a magnetic stirrer bar was taken into
the glovebox and charged sequentially with diphenyl diselenide (PhSeSePh) (15.8 mg, 0.05
mmol, 5 mol %), benzyltriethylammonium chloride (BnEt3NCl) (690 mg, 3.03 mmol, 3.0 equiv),
and N-fluoropyridinium tetrafluoroborate 11 (240 mg, 1.30 mmol, 1.3 equiv), and was then
sealed with a rubber septum, removed from the box, and placed under argon. MeCN-d3 (5.0 mL),
1,1,2,2-tetrachloroethane (168 mg, 106 µL, 1.00 mmol, 1.0 equiv), 2,6-lutidine N-oxide 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), and chlorotrimethylsilane (Me3SiCl) (218 mg, 255 µL, 2.01
mmol, 2.0 equiv) were then added sequentially and stirring was commenced. After ca. 10 min, an
off-white suspension (occasionally with yellow tinges) was observed. At this point, the requisite
alkene (1.00 mmol, 1.0 equiv) was transferred via syringe to the reaction mixture, and the
resultant suspension was stirred at rt. At the time stated, stirring was interrupted to let any solids
settle to the bottom of the flask and an aliquot (0.5 mL) was transferred via syringe into an oven-
dried NMR tube. The reaction was analyzed by 1H NMR spectroscopy to determine the NMR
yield and syn/anti diastereoisomeric ratio (dr).
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NMR Study on Formation of (u)-1,2-Dichlorocyclohexane (7)
Following General Procedure VI, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN-d3 (5.0 mL),
1,1,2,2-tetrachloroethane (174 mg, 110 µL, 1.04 mmol, 1.0 equiv), 23 (126 mg, 115 µL, 1.02
mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and cyclohexene 6 (85.2
mg, 105 µL, 1.04 mmol, 1.0 equiv) were reacted for 10 h to give a red-brown suspension.
Analysis by 1H NMR spectroscopy showed almost complete conversion of cyclohexene 6 had
occurred to give (u)-1,2-dichlorocyclohexane 7 (80% NMR yield, >99:1 dr) and allylic chloride
by-product 8 (4% NMR yield). (Note: For diagnostic 1H NMR resonances for 7 and 8 see
General Procedure I). Extension of the reaction time to 24 h gave complete consumption of
cyclohexene 6 but only a negligible increase in the amount of 7 (82% NMR yield, >99:1 dr) and
8 (6% NMR yield).
NMR Study on Formation of (u)-1,2-Dichlorocycloheptane (29a)
Following General Procedure VI, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN-d3 (5.0 mL),
1,1,2,2-tetrachloroethane (174 mg, 110 µL, 1.04 mmol, 1.0 equiv), 23 (126 mg, 115 µL, 1.02
mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and cycloheptene 28a (98.9
mg, 120 µL, 1.03 mmol, 1.0 equiv) were reacted for 4 h to give a red-brown suspension.
Analysis by 1H NMR spectroscopy showed complete conversion of cycloheptene 28a had
occurred to give (u)-1,2- dichlorocycloheptane 29a (96% NMR yield, 99:1 dr) and allylic
chloride by-product S22 (ca. 3% NMR yield).
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Data for 29a: 1H NMR: (400 MHz, MeCN-d3, diagnostic resonances only)
δ 4.52–4.47 (m, 2 H, HC(1,2))
Data for the anti-diastereoisomer of 29a: 1H NMR: (400 MHz, MeCN-d3, diagnostic resonances only)
δ 4.33–4.28 (m, 2 H, HC(1,2))
Data for S20: 1H NMR: (400 MHz, MeCN-d3, diagnostic resonances only)
δ 5.86–5.76 (m, 2 H, HC(2,3))
NMR Study on Formation of (l)-4,5-Dichlorooctane (29g)
Following General Procedure VI, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN-d3 (5.0 mL),
1,1,2,2-tetrachloroethane (174 mg, 110 µL, 1.04 mmol, 1.0 equiv), 23 (126 mg, 115 µL, 1.02
mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and (E)-4-octene 28g (98.9
mg, 160 µL, 1.02 mmol, 1.0 equiv) were reacted for 4 h to give an orange-red suspension.
Analysis by 1H NMR spectroscopy showed complete conversion of (E)-4-octene 28g had
occurred to give (l)-4,5-dichlorooctane 29g (66% NMR yield, 99:1 dr) and tentatively assigned
vinylic and allylic chlorides by-products (S21 + S22) (ca. 34% combined yield).
Data for 29g: 1H NMR: (400 MHz, MeCN-d3, diagnostic resonances only)
δ 4.20–4.14 (m, 2 H, HC(4,5))
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Data for the anti-diastereoisomer of 29g: 1H NMR: (400 MHz, MeCN-d3, diagnostic resonances only)
δ 4.00–3.96 (m, 2 H, HC(4,5))
Data for (S21 + S22): 1H NMR: (400 MHz, MeCN-d3, diagnostic resonances only)
δ 5.76 & 5.73 (t, J = 6.4 Hz, 1 H, HC(4) for S22), 5.58 (t, J = 7.8 Hz, 1 H, HC(5)
for S21), 5.51 & 5.47 (dt, J = 8.9, 1.5 Hz, 1 H, HC(3) for S22)
General Procedure VII: Catalytic, syn-Dichlorination of Alkenes with 2,6-Lutidine N-
Oxide as Additive (Table 3)
An oven-dried, 10-mL Schlenk flask equipped with a magnetic stirrer bar was taken into
the glovebox and charged sequentially with diphenyl diselenide (PhSeSePh) (15.8 mg, 0.05
mmol, 5 mol %), benzyltriethylammonium chloride (BnEt3NCl) (690 mg, 3.03 mmol, 3.0 equiv),
and N-fluoropyridinium tetrafluoroborate 11 (240 mg, 1.30 mmol, 1.3 equiv), and was then
sealed with a rubber septum, removed from the box, and placed under argon. MeCN (5.0 mL),
2,6-lutidine N-oxide 23 (126 mg, 115 µL, 1.02 mmol, 1.0 equiv), and chlorotrimethylsilane
(Me3SiCl) (218 mg, 255 µL, 2.01 mmol, 2.0 equiv) were then added sequentially and stirring
was commenced. After ca. 10 min, an off-white suspension (occasionally with yellow tinges)
was observed. At this point, the requisite alkene (1.00 mmol, 1.0 equiv) was transferred via
syringe to the reaction mixture [for alkenes of unknown density, only 3.0 mL of MeCN was
added initially and the remaining 2.0 mL (in two 1.0 mL portions) was used to transfer the
alkene across from an oven-dried, 4-mL dram vial under an argon atmosphere, via syringe]. The
resultant suspension was stirred at rt, and was monitored by TLC until no alkene substrate could
be detected. Once the reaction had reached completion, sat. aq. NaHCO3 (1.0 mL) was added to
quench any unreacted chlorotrimethylsilane. After stirring for ca. 10 min at rt, the resultant
mixture was transferred to a separatory funnel and diluted with H2O (15 mL). The aqueous layer
was extracted with Et2O (3 × 15 mL), and the combined organic extracts were washed with brine
(15 mL), then dried (MgSO4), filtered, and concentrated in vacuo (20–23 °C, ca. 20 mm Hg for
non-volatile products or 5–8 °C, ca. 20 mm Hg for volatile products). The resultant residue was
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re-dissolved in Et2O (5.0 mL) and eluted through a short plug of silica gel (ca. 0.55 g SiO2
packed into a Pasteur pipet to a height of ca. 40 mm) in order to partially remove 2,6-lutidine N-
oxide and any ammonium salts, and the plug was then rinsed through with further portions of
Et2O (3 × 5 mL). The solvent was removed in vacuo (20–23 °C, ca. 20 mm Hg for non-volatile
products or 5–8 °C, ca. 20 mm Hg for volatile products), and an aliquot of the crude mixture was
dissolved in CDCl3 to measure the syn/anti diastereoisomeric ratio (dr) by 1H NMR spectroscopy.
The syn-dichloride product was then isolated as described.
Preparation of (u)-1,2-Dichlorocyclohexane (7) (Table 3)
Following General Procedure VII (but on double the scale in a 25-mL Schlenk flask),
PhSeSePh (31.4 mg, 0.10 mmol, 5 mol %), BnEt3NCl (1.375 g, 6.04 mmol, 3.0 equiv), 11 (486
mg, 2.63 mmol, 1.3 equiv), MeCN (10.0 mL), 23 (246 mg, 225 µL, 2.00 mmol, 1.0 equiv),
Me3SiCl (445 mg, 520 µL, 4.10 mmol, 2.0 equiv), and cyclohexene 6 (166 mg, 205 µL, 2.02
mmol, 1.0 equiv) were reacted for 10 h. (Note: TLC was indeterminate in this case due to the
volatility of cyclohexene and the reaction time was instead based on a previous test reaction
monitored by 1H NMR spectroscopy). A red-brown suspension was obtained which, following
the work-up described in the general procedure, gave an orange oil (>99:1 dr). Caution: the
product is volatile and should not be left on the rotary evaporator for an extended period.
Purification via flash column chromatography [33 g high porosity grade SiO2, 34 mm Ø, wet
loaded, petroleum ether (500 mL), ca. 10 mL fractions] gave a yellow oil (174 mg, ca. 95%
purity) (N.B. solvent was removed in vacuo at 5–8 °C, ca. 20 mm Hg). Further purification via
Kugelrohr distillation at reduced pressure (15 mm Hg) gave 7 as a clear, colorless oil (156 mg,
51%).
Data for 7: bp: 90 °C (ABT) (15 mm Hg)
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1H NMR: (500 MHz, CDCl3)
δ 4.29–4.27 (m, 2 H, HC(1,2)), 2.15–2.09 (m, 2 H, HC(3,6)), 1.89–1.83 (m, 2 H,
HC(3,6)), 1.83–1.76 (m, 2 H, HC(4,5)), 1.46–1.39 (m, 2 H, HC(4,5)) 13C NMR: (126 MHz, CDCl3)
δ 62.7 (C(1,2)), 32.3 (C(3,6)), 22.1 (C(4,5))
IR: (neat)
2944 (s), 2856 (m), 1447 (m), 1356 (w), 1313 (w), 1290 (w), 1274 (m), 1227 (w),
1192 (w), 1132 (w), 1084 (w), 1056 (w), 1267 (w), 986 (m), 907 (m), 877 (m), 834
(m), 817 (m), 741 (m), 694 (m)
MS: (EI+, TOF)
154.0 (18), 152.0 (M+, 30), 118.0 (26), 116.0 (100), 90.0 (11), 88.0 (23), 81.6 (20),
81.1 (27), 80.0 (53), 79.0 (81), 77.0 (15), 75.0 (53), 67.1 (52), 62.0 (12), 55.1 (16),
54.0 (13), 53.0 (15)
HRMS: (EI+, TOF)
calcd for C6H10Cl2 (M+): 152.0160, found: 152.0161
TLC: Rf 0.44 (hexane) [CAM; developed at <300 °C, white spot against yellow
background which quickly disappeared with further and/or stronger heating]
Analysis: C6H10Cl2 (153.05)
Calcd: C, 47.09; H, 6.59%
Found: C, 47.05; H, 6.51%
Preparation of (u)-1,2-Dichlorocycloheptane (29a) (Table 3)
Following General Procedure VII (but on double the scale in a 25-mL Schlenk flask),
PhSeSePh (31.2 mg, 0.10 mmol, 5 mol %), BnEt3NCl (1.373 g, 6.03 mmol, 3.0 equiv), 11 (483
mg, 2.61 mmol, 1.3 equiv), MeCN (10.0 mL), 23 (246 mg, 225 µL, 2.00 mmol, 1.0 equiv),
Me3SiCl (445 mg, 520 µL, 4.10 mmol, 2.0 equiv), and cycloheptene 28a (194 mg, 235 µL, 2.01
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mmol, 1.0 equiv) were reacted for 4 h to give a red-brown suspension which, following the
work-up described in the general procedure, gave an orange-red oil (99:1 dr). Caution: the
product is volatile and should not be left on the rotary evaporator for an extended period.
Purification via flash column chromatography [27 g high porosity grade SiO2, 24 mm Ø,
wet loaded, pentane (500 mL), ca. 10 mL fractions] gave a yellow oil (268 mg) (N.B. solvent
was removed in vacuo at 5–8 °C, ca. 20 mm Hg). Further purification via two successive
Kugelrohr distillations at reduced pressure (10 mm Hg) gave 29a as a clear, colorless oil (256
mg, 77%).
Data for 29a: bp: 118 °C (ABT) (10 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 4.41–4.39 (m, 2 H, HC(1,2)), 2.22–2.15 (m, 2 H, HC(3,7)), 2.01–1.94 (m, 2 H,
HC(3,7)), 1.81–1.68 (m, 3 H, HC(4,5,6)), 1.62–1.46 (m, 3 H, HC(4,5,6)) 13C NMR: (126 MHz, CDCl3)
δ 66.2 (C(1,2)), 34.1 (C(3,7)), 25.6 (C(5)), 23.4 (C(4,6))
IR: (neat)
2936 (s), 2863 (m), 2693 (w), 1455 (m), 1434 (w), 1361 (s), 1315 (s), 1285 (w),
1233 (w), 1196 (w), 1150 (w), 1047 (w), 1004 (w), 977 (w), 942 (w), 915 (w), 882
(w), 863 (w), 840(w), 822 (w), 795 (w), 769 (w), 716 (w), 685 (m), 643 (w)
MS: (CI+, DFSF)
131.0 ([M–Cl]+, 7), 129.0 ([(M–HCl)-H]+, 6), 96.1 ([M–2Cl]+, 25), 95.1 ([(M–
HCl)–Cl]+, 100), 94.1 (22), 81.1 (11), 79.1 (12), 68.0 (12), 63.0 (27), 59.0 (12),
55.0 (12)
HRMS: (CI+, DFSF)
calcd for C7H10Cl [(M–HCl)-H]+: 129.04721, found: 129.04710
TLC: Rf 0.46 (hexane) [CAM; developed at <300 °C, white spot against yellow
background which quickly disappeared with further and/or stronger heating]
Analysis: C7H12Cl2 (167.07)
Calcd: C, 50.32; H, 7.24%
Found: C, 50.58; H, 7.02%
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Preparation of [1r-(u)-3,4-Dichlorocyclopentyl]methyl acetate (29b) (Table 3)
Following General Procedure VII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (242 mg, 1.31 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28b (141 mg, 1.01 mmol, 1.0 equiv) were reacted for 24 h (TLC analysis showed that a
trace amount of 28b remained). Following the work-up described in the general procedure, a
89:11 mixture of dichlorides 29b [diastereoisomeric at C(1)] was obtained as an orange oil
(>99:1 syn/anti dichloride ratio w.r.t. the major diastereoisomer). Purification via flash column
chromatography [74 g SiO2, 34 mm Ø, dry loaded with 2.4 g SiO2, 92:8 hexane/EtOAc (1 L), ca.
10 mL fractions] gave a colourless oil [159 mg, 91:9 dr at C(1)]. Caution: the product is volatile
at ca. 0.05 mm Hg. Further purification via Kugelrohr distillation at reduced pressure (0.05 mm
Hg) gave 29b as a clear, colorless oil [155 mg, 73%, 91:9 dr at C(1)]. By analogy to known syn-
and anti-epoxy ethers of 1-hydroxymethyl-3-cyclopentene,26 the relative configuration at C(1) in
29b was determined by chemical correlation with 29c [which was compared to an authentic
sample (vide infra)]. HC(6) of the major syn-diastereoisomer [at C(1)] has a larger vicinal 1H-1H 3J coupling constant (3Jsyn = 7.2 Hz versus 3Janti = 6.0 Hz) and is shifted downfield [δ HC(6)syn =
4.11 versus δ HC(6)anti = 3.99] than HC(6) of the corresponding minor anti-diastereoisomer [at
C(1)].
Data for 29b: bp: 71 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 4.36–4.33 (m, 2 H, HC(3,4), minor diastereoisomer), 4.31–4.28 (m, 2 H, HC(3,4),
major diastereoisomer), 4.11 (d, J = 7.2 Hz, 2 H, HC(6), major diastereoisomer),
3.99 (d, J = 6.0 Hz, 2 H, HC(6), minor diastereoisomer), 2.85–2.77 (m, 1 H, HC(1),
minor diastereoisomer), 2.47–2.26 (m, 3 H for major diastereoisomer, 2 H for
minor diastereoisomer, HC(1) for major diastereoisomer, HC(2,5) for both
diastereoisomers), 2.06 (s, 3 H, HC(8), minor diastereoisomer), 2.05 (s, 3 H, HC(8),
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major diastereoisomer), 2.03–1.91 (m, 2 H each, HC(2,5), both diastereoisomers) 13C NMR: (126 MHz, CDCl3)
δ 170.9 (C(7), both diastereoisomers), 68.1 (C(6), major diastereoisomer), 66.9
(C(6), minor diastereoisomer), 62.6 (C(3,4), minor diastereoisomer), 62.0 (C(3,4),
major diastereoisomer), 36.1 (C(2,5), major diastereoisomer), 36.0 (C(2,5), minor
diastereoisomer), 34.2 (C(1), major diastereoisomer), 33.7 (C(1), minor
diastereoisomer), 20.9 (C(8), both diastereoisomers)
IR: (neat)
3445 (w), 2976 (w), 2951 (w), 2898 (w), 2856 (w), 1741 (s), 1441 (m), 1388 (w),
1367 (m), 1311 (w), 1239 (s), 1135 (m), 1042 (m), 996 (w), 950 (w), 893 (w), 794
(w), 640 (w), 614 (w)
MS: (ESI+, TOF)
235.0 (30), 233.0 ([M+Na]+, 45), 209.0 (33), 208.0 (16), 207.2 (34), 207.0 (87),
206.0 (20), 205 (100), 187 (10)
HRMS: (ESI+, TOF)
calcd for C8H12Cl2NaO2 [M+Na]+: 233.0112, found: 233.0112
TLC: Rf 0.23 (92:8 hexane/EtOAc) [KMnO4]
Analysis: C8H12Cl2O2 (211.08)
Calcd: C, 45.52; H, 5.73%
Found: C, 45.55; H, 5.57%
Preparation of tert-Butyl{[1r-(u)-3,4-dichlorocyclopentyl]methoxy}diphenylsilane (29c)
(Table 3)
Following General Procedure VII, PhSeSePh (15.6 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
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alkene 28c (337 mg, 1.00 mmol, 1.0 equiv) were reacted for 16 h to give an orange suspension
which, following the work-up described in the general procedure, gave a 91:9 mixture of
dichlorides 29c [diastereoisomeric at C(1)] as an orange oil (>99:1 syn/anti dichloride ratio w.r.t.
the major diastereoisomer). Purification via flash column chromatography [48 g high porosity
grade SiO2, 30 mm Ø, dry loaded with 1.8 g SiO2, 98:2 petroleum ether/MTBE (700 mL), ca. 10
mL fractions] gave a colourless oil [292 mg, 91:9 dr at C(1)]. Further purification via Kugelrohr
distillation at reduced pressure (0.05 mm Hg) gave 29c as a clear, colorless, viscous oil [288 mg,
71%, 91:9 dr at C(1)]. The relative configuration at C(1) in 29c was determined by comparison
with authentic samples of both diastereoisomers obtained via deoxochlorination of the
corresponding epoxides under Appel-type conditions.27
Data for 29c: bp: 186 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.68–7.62 (m, 4 H each, HC(2′,2′′), both diastereoisomers), 7.46–7.37 (m, 6 H
each, HC(3′,4′,3′′,4′′), both diastereoisomers), 4.39–4.36 (m, 2 H, HC(3,4), minor
diastereoisomer), 4.31–4.26 (m, 2 H, HC(3,4), major diastereoisomer), 3.69 (d, J =
6.8 Hz, 2 H, HC(6), major diastereoisomer), 3.57 (d, J = 5.0 Hz, 2 H, HC(6), minor
diastereoisomer), 2.70–2.62 (m, 1 H, HC(1), minor diastereoisomer), 2.37–2.20 (m,
3 H for major diastereoisomer, 2 H for minor diastereoisomer, HC(1) for major
diastereoisomer, HC(2,5) for both diastereoisomers), 2.10–1.98 (m, 2 H each,
HC(2,5), both diastereoisomers), 1.06 (s, 9 H, Sit-Bu, both diastereoisomers) 13C NMR: (126 MHz, CDCl3)
δ 135.5 (C(2′,2′′), both diastereoisomers), 133.6 (C(1′,1′′), major diastereoisomer),
133.3 (C(1′,1′′), minor diastereoisomer), 129.8 (C(4′,4′′), minor diastereoisomer),
129.6 (C(4′,4′′), major diastereoisomer), 127.74 (C(3′,3′′), minor diastereoisomer),
127.66 (C(3′,3′′), major diastereoisomer), 67.9 (C(6), major diastereoisomer), 66.2
(C(6), minor diastereoisomer), 63.4 (C(3,4), minor diastereoisomer), 62.3 (C(3,4),
major diastereoisomer), 37.7 (C(1), major diastereoisomer), 36.8 (C(1), minor
diastereoisomer), 35.9 (C(2,5), major diastereoisomer), 35.7 (C(2,5), minor
diastereoisomer), 26.87 (SiCMe3, minor diastereoisomer), 26.82 (SiCMe3, major
diastereoisomer), 19.3 (SiCMe3, both diastereoisomers)
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IR: (neat)
3071 (m), 3050 (w), 2931 (m), 2894 (w), 2858 (m), 2742 (w), 1961 (w), 1893 (w),
1824 (w), 1590 (w), 1472 (m), 1428 (m), 1388 (w), 1361 (w), 1312 (w), 1277 (w),
1257 (w), 1112 (s), 1030 (w), 1008 (w), 998 (w), 975 (w), 949 (w), 916 (w), 892
(w), 824 (m), 798 (m), 740 (m), 702 (m), 642 (w), 613 (m)
MS: (ESI+, TOF)
407.2 ([M+H]+, 10), 339.4 (25), 338.4 ([M–2Cl]+, 100), 284.3 (13), 257.2 (11),
151.0 (10)
HRMS: (ESI+, TOF)
calcd for C22H29Cl2OSi ([M+H]+): 407.1365, found: 407.1368
TLC: major diastereoisomer – Rf 0.22 (99:1 hexane/MTBE) [UV/KMnO4]
minor diastereoisomer – Rf 0.29 (99:1 hexane/MTBE) [UV/KMnO4]
Analysis: C22H28Cl2OSi (407.45)
Calcd: C, 64.85; H, 6.93%
Found: C, 64.86; H, 6.74%
Preparation of tert-Butyl(3,4-dichlorobutoxy)diphenylsilane (29d) (Table 3)
Following General Procedure VII, PhSeSePh (15.7 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (241 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28d (311 mg, 1.00 mmol, 1.0 equiv) were reacted for 6 h to give a yellow-brown
suspension which, following the work-up described in the general procedure, gave a yellow oil.
Purification via flash column chromatography [62 g high porosity grade SiO2, 34 mm Ø, dry
loaded with 2.2 g SiO2, 100:0 → 99:1 → 98:2 hexane/MTBE (2 L, 500 mL, and 400 mL,
respectively), ca. 10 mL fractions] gave a clear, pale yellow oil (350 mg). Further purification
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via Kugelrohr distillation at reduced pressure (0.05 mm Hg) gave 29d as a clear, colorless,
viscous oil, which solidified to a white solid on standing in a –20 °C freezer for ca. 3 days (346
mg, 91%). The 1H and 13C NMR spectroscopic data matched that for alternative preparations.28
Data for 29d: bp: 163 °C (ABT) (0.05 mm Hg)
mp: 38–40 °C
1H NMR: (500 MHz, CDCl3)
δ 7.73–7.66 (m, 4 H, HC(2′,2′′)), 7.49–7.38 (m, 6 H, HC(3′,3′′,4′,4′′)), 4.46–4.38 (m,
1 H, HC(3)), 3.95–3.80 (m, 3 H, HC(1,4)), 3.76 (dd, J = 11.4, 6.9 Hz, 1 H, HC(4)),
2.34–2.25 (m, 1 H, HC(2)), 1.87 (app ddt, J = 14.0, 9.0, 4.3 Hz, 1 H, HC(2)), 1.09
(s, 9 H, Sit-Bu) 13C NMR: (126 MHz, CDCl3)
δ 135.54 & 135.51 (C(2′,2′′)), 133.4 & 133.3 (C(1′,1′′)), 129.73 (C(4′,4′′)), 127.7
(C(3′,3′′)), 60.0 (C(1)), 58.0 (C(3)), 48.7 (C(4)), 37.9 (C(2)), 26.8 (SiCMe3), 19.2
(SiCMe3)
IR: (neat)
3071 (w), 3050 (w), 2958 (m), 2931 (m), 2883 (w), 2858 (m), 1589 (w), 1472 (m),
1428 (m), 1390 (w), 1362 (w), 1293 (w), 1267 (w), 1195 (w), 1112 (s), 1091 (m),
998 (w), 941 (w), 823 (m), 757 (w), 738 (m), 701 (s), 688 (w), 664 (w), 614 (m)
MS: (ESI+, TOF)
399.2 (10), 381.1 ([M+H]+, 9), 377.2 (17), 360.2 (20), 359.2 (100), 283.2 (23),
150.0 (15), 149.0 (16), 125.0 (11), 124.1 (57), 111.1 (21)
HRMS: (ESI+, TOF)
calcd for C20H27Cl2OSi ([M+H]+): 381.1208, found: 381.1213
TLC: Rf 0.51 (99:1 hexane/MTBE) [UV/KMnO4]
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Preparation of 4-(3,4-Dichlorobutyl)-2,2-dimethyl-1,3-dioxolane (29e) (Table 3)
Following General Procedure VII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (241 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28e (156 mg, 1.00 mmol, 1.0 equiv) were reacted for 4.5 h to give a yellow-brown
suspension which, following the work-up described in the general procedure, gave a 1:1
diastereoisomeric mixture of dichlorides 29e as an orange oil. Purification via flash column
chromatography [45 g SiO2, 34 mm Ø, dry loaded with 1.8 g SiO2, 92:8 hexane/Et2O (700 mL),
ca. 10 mL fractions] gave a colourless oil (205 mg, 1:1 dr). Caution: the product is volatile at ca.
0.05 mm Hg. Further purification via Kugelrohr distillation at reduced pressure (5 mm Hg) gave
29e as a clear, colorless oil (194 mg, 85%, 1:1 dr). An analytically pure sample was obtained by
further purification of an aliquot (180 mg) of 29e via Kugelrohr distillation at reduced pressure
(1 mm Hg) to give a clear, colourless oil (172 mg, 95% mass return).
Data for 29e: bp: 118 °C (ABT) (5 mm Hg) / 90 °C (ABT) (1 mm Hg)
1H NMR: (500 MHz, CDCl3) (N.B. *diastereoisomeric pair)
δ 4.16–4.04 (m, 3 H, HC(3,4′,5′) & HC(3,4′,5′)*), 3.78 (ddd, J = 11.4, 5.1, 3.2 Hz, 1
H, HC(4) & HC(4)*), 3.66 (ddd, J = 11.5, 7.5, 4.1 Hz, 1 H, HC(4) & HC(4)*), 3.55
(app q, J = 7.4 Hz, 1 H, HC(5′) & HC(5′)*), 2.23–2.15 (m, 1 H, HC(2)), 2.11–2.03
(m, 1 H, HC(2)*), 1.92–1.79 (m, 3 H, HC(1,2*)), 1.76–1.63 (m, 3 H, HC(1*,2)),
1.41 (s, 3 H, HC(6′) & HC(6′)*), 1.35 (s, 3 H, HC(7′) & HC(7′)*) 13C NMR: (126 MHz, CDCl3)
δ 109.1 (C(2′)), 109.0 (C(2′)*), 75.6 (C(4′)), 75.0 (C(4′)*), 69.3 (C(5′)), 69.2
(C(5′)*), 61.0 (C(3), 60.7 (C(3)*), 48.1 (C(4)), 48.0 (C(4)*), 31.7 (C(2)), 31.1
(C(2)*), 30.2 (C(1)), 29.8 (C(1)*), 26.9 (C(6′),C(6′)*), 25.64 (C(7′)), 25.59 (C(7′)*)
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IR: (neat)
2986 (m), 2937 (w), 2873 (w), 1445 (w), 1380 (m), 1371 (m), 1215 (m), 1154 (m),
1065 (m), 980 (w), 853 (m), 796 (w), 735 (w), 664 (w)
MS: (EI+, TOF)
213.0 (57), 211.0 ([M–CH3]+, 100), 153.0 (13), 151.0 (19), 115.0 (18), 79.1 (41),
72.1 (19)
HRMS: (EI+, TOF)
calcd for C8H13Cl2O2 ([M–CH3]+): 211.0293, found: 211.0294
TLC: Rf 0.22 (96:4 hexane/EtOAc) [KMnO4]
Analysis: C9H16Cl2O2 (227.13)
Calcd: C, 47.59; H, 7.10%
Found: C, 47.44; H, 7.03%
Preparation of 5-(2,3-Dichloropropyl)benzo[d][1,3]dioxole (29f) (Table 3)
Following General Procedure VII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (241 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
safrole 28f (164 mg, 150 µL, 1.01 mmol, 1.0 equiv) were reacted for 3.5 h to give a yellow-
brown suspension which, following the work-up described in the general procedure, gave a
yellow oil. Purification via flash column chromatography [65 g SiO2, 34 mm Ø, dry loaded with
2.0 g SiO2, 100:0 → 99:1 hexane/MTBE (2 L and 1.5 L, respectively), ca. 10 mL fractions then
25 g SiO2, 24 mm Ø, wet loaded, 100:0 → 99:1 hexane/Et2O (both 300 mL), ca. 10 mL
fractions] gave a clear, pale yellow oil (182 mg). Further purification via Kugelrohr distillation at
reduced pressure (0.05 mm Hg) gave 29f as a clear, pale yellow oil (180 mg, 77%).
Data for 29f:
bp: 118 °C (ABT) (0.05 mm Hg)
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1H NMR: (500 MHz, CDCl3)
δ 6.79–6.70 (m, 3 H, HC(3′,4′,6′)), 5.96 (s, 2 H, HC(7′)), 4.23–4.18 (m, 1 H, HC(2)),
3.72 (dd, J = 11.4, 4.7 Hz, 1 H, HC(3)), 3.65 (dd, J = 11.4, 6.9 Hz, 1 H, HC(3)),
3.21 (dd, J = 14.3, 5.7 Hz, 1 H, HC(1)), 2.99 (dd, J = 14.3, 7.1 Hz, 1 H, HC(1)) 13C NMR: (126 MHz, CDCl3)
δ 147.7 (C(1′)), 146.7 (C(2′)), 129.8 (C(5′)), 122.7 (C(4′)), 109.8 (C(6′)), 108.3
(C(3′)), 101.0 (C(7′)), 61.0 (C(2)), 47.3 (C(3)), 40.6 (C(1))
IR: (neat)
2895 (w), 2778 (w), 1852 (w), 1608 (w), 1504 (m), 1490 (m), 1444 (m), 1364 (w),
1250 (m), 1191 (m), 1123 (w), 1100 (w), 1039 (m), 992 (w), 930 (m), 879 (m), 810
(w), 776 (w), 724 (w), 669 (w), 601 (w)
MS: (EI+, TOF)
234.0 (11), 232.0 (M+, 18), 135.0 ([M–C2H3Cl2]+, 100), 77.0 (10)
HRMS: (EI+, TOF)
calcd for C10H10Cl2O2 (M+): 232.0058, found: 232.0057
TLC: Rf 0.46 (96:4 hexane/EtOAc) [UV/KMnO4]
Analysis: C10H10Cl2O2 (233.09)
Calcd: C, 51.53; H, 4.32%
Found: C, 51.71; H, 4.22%
Preparation of (l)-4,5-Dichlorooctane (29g) (Table 3)
Following General Procedure VII (but on double the scale in a 25-mL Schlenk flask),
PhSeSePh (31.8 mg, 0.10 mmol, 5 mol %), BnEt3NCl (1.388 g, 6.09 mmol, 3.0 equiv), 11 (492
mg, 2.66 mmol, 1.3 equiv), MeCN (10.0 mL), 23 (246 mg, 225 µL, 2.00 mmol, 1.0 equiv),
Me3SiCl (445 mg, 520 µL, 4.10 mmol, 2.0 equiv), and (E)-4-octene 28g (229 mg, 320 µL, 2.04
mmol, 1.0 equiv) were reacted for 4 h to give an orange-red solution which, following the work-
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up described in the general procedure, gave an orange oil (99:1 dr). Caution: the product is
highly volatile and should not be left on the rotary evaporator for an extended period.
Purification via flash column chromatography [92 g high porosity grade SiO2, 30 mm Ø, wet
loaded, petroleum ether (500 mL), ca. 10 mL fractions] gave a yellow oil (249 mg, ≥90% purity)
(N.B. solvent was removed in vacuo at 5–8 °C, ca. 20 mm Hg). Further purification via
Kugelrohr distillation at reduced pressure (20 mm Hg) gave 29g as a clear, colorless oil (151 mg,
40%, contaminated with 3% vinylic chloride by-product). A yellow residue (79.0 mg) containing
29g (≥90%) and an inseparable, unidentified selenium-containing by-product remained, which
was not purified further.
Data for 29g: bp: 120 °C (ABT) (20 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 4.07–4.04 (m, 2 H, HC(4,5)), 1.92–1.84 (m, 2 H, HC(3,6)), 1.83–1.75 (m, 2 H,
HC(3,6)), 1.66–1.55 (m, 2 H, HC(2,7)), 1.47–1.36 (m, 2 H, HC(2,7)), 0.95 (t, J =
7.4 Hz, 6 H, HC(1,8)) 13C NMR: (126 MHz, CDCl3)
δ 65.3 (C(4,5)), 36.4 (C(3,6)), 19.9 (C(2,7)), 13.5 (C(1,8))
IR: (neat)
2962 (s), 2935 (m), 2875 (m), 1466 (m), 1461 (m), 1433 (w), 1382 (w), 1274 (w),
1257 (w), 1206 (w), 1122(w), 1049 (w), 985(w), 876 (w), 764 (w), 751 (m), 721
(w), 647(m)
MS: (EI+, TOF)
182.1 (M+, 5), 148.1 (22), 146.1 ([M–Cl]+, 65), 111.1 ([M–2Cl]+, 88), 110.1 (58),
55.1 (100)
HRMS: (EI+, TOF)
calcd for C8H16Cl2 (M+): 182.0629, found: 182.0628
TLC: Rf 0.66 (hexane) [CAM; developed at <300 °C, white spot against yellow
background which quickly disappeared with further and/or stronger heating]
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Preparation of (l)-{[(4,5-Dichlorohexyl)oxy]methyl}benzene (18) (Table 3)
Following General Procedure VII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 17 (191 mg, 1.00 mmol, 1.0 equiv) were reacted for 3.5 h to give a yellow-brown
suspension which, following the work-up described in the general procedure, gave a yellow oil
(99:1 dr). Purification via flash column chromatography [69 g SiO2, 34 mm Ø, dry loaded with
1.9 g SiO2, 98:2 hexane/Et2O (1.1 L), ca. 10 mL fractions] gave a pale yellow oil (190 mg).
Further purification via Kugelrohr distillation at reduced pressure (0.05 mm Hg) gave 18 as a
clear, colorless oil (185 mg, 71%).
Data for 18: bp: 118 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.38–7.27 (m, 5 H, HC(2′,3′,4′)), 4.53 & 4.51 (ABq, JAB = 12.0 Hz, 2 H, HC(5′)),
4.26 (qd, J = 6.7, 3.0 Hz, 1 H, HC(5)), 4.04 (dt, J = 9.9, 3.2 Hz, 1 H, HC(4)), 3.57–
3.49 (m, 2 H, HC(1)), 2.13–2.05 (m, 1 H, HC(3)), 1.96–1.80 (m, 2 H, HC(2,3)),
1.77–1.69 (m, 1 H, HC(2)), 1.58 (d, J = 6.7 Hz, 3 H, HC(6)) 13C NMR: (126 MHz, CDCl3)
δ 138.3 (C(1′)), 128.4 (C(3′)), 127.63 (C(2′)), 127.59 (C(4′)), 72.9 (C(5′)), 69.4
(C(1)), 66.1 (C(4)), 60.0 (C(5)), 30.9 (C(3)), 26.9 (C(2)), 20.8 (C(6))
IR: (neat)
3399 (w), 3030 (w), 2928 (m), 2857 (m), 2795 (w), 1496 (w), 1453 (m), 1381 (w),
1362 (w), 1104 (s), 1028 (m), 996 (w), 913 (w), 737 (m), 698 (m), 615 (m)
MS: (ESI+, TOF)
437.2 (23), 415.2 (38), 413.3 (13), 381.3 (25), 359.2 (27), 341.3 (20), 284.3 (43),
282.3 (74), 263.1 (31), 261.1 ([M+H]+, 40), 256.3 (45), 229.2 (61), 189.1 (27),
185.1 (49), 124.1 ([(M–CH2OCH2Ph)-CH3]+, 93), 91.1 ([CH2Ph]+, 100)
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HRMS: (ESI+, TOF)
calcd for C13H19Cl2O ([M+H]+): 261.0813, found: 261.0826
TLC: Rf 0.31 (98:2 hexane/EtOAc) [UV/KMnO4]
Analysis: C13H18Cl2O (261.19)
Calcd: C, 59.78; H, 6.95%
Found: C, 60.06; H, 6.84%
Preparation of (u)-{[(4,5-Dichlorohexyl)oxy]methyl}benzene (29h) (Table 3)
Following General Procedure VII, PhSeSePh (15.6 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28h (191 mg, 1.00 mmol, 1.0 equiv) were reacted for 4 h to give a yellow-brown
suspension which, following the work-up described in the general procedure, gave a yellow oil
(>99:1 dr). Purification via flash column chromatography [75 g SiO2, 34 mm Ø, dry loaded with
2.2 g SiO2, 99:1 hexane/EtOAc (1.5 L), ca. 10 mL fractions], followed by further purification of
the mixed fractions [52 g high porosity grade SiO2, 34 mm Ø, dry loaded with 1.8 g SiO2,
98.4:1.6 hexane/MTBE (1 L), ca. 10 mL fractions], gave a pale yellow oil (176 mg). Further
purification via Kugelrohr distillation at reduced pressure (0.05 mm Hg) gave 29h as a clear,
colorless oil (175 mg, 67%).
Data for 29h: bp: 118 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.37–7.27 (m, 5 H, HC(2′,3′,4′)), 4.53 & 4.50 (ABq, JAB = 12.0 Hz, 2 H, HC(5′)),
4.11 (app pent, J = 6.5 Hz, 1 H, HC(5)), 3.98 (ddd, J = 9.5, 6.4, 2.9 Hz, 1 H, HC(4)),
3.56–3.48 (m, 2 H, HC(1)), 2.18–2.12 (m, 1 H, HC(3)), 1.98–1.90 (m, 1 H, HC(2)),
1.85–1.70 (m, 2 H, HC(2,3)), 1.62 (d, J = 6.6 Hz, 3 H, HC(6))
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13C NMR: (126 MHz, CDCl3)
δ 138.4 (C(1′)), 128.4 (C(3′)), 127.62 (C(2′)), 127.58 (C(4′)), 72.9 (C(5′)), 69.3
(C(1)), 67.1 (C(4)), 60.2 (C(5)), 31.9 (C(3)), 26.5 (C(2)), 21.9 (C(6))
IR: (neat)
3087 (w), 3064 (w), 3031 (w), 2983 (w), 2935 (m), 2858 (m), 2795 (w), 1496 (w),
1454 (m), 1380 (w), 1362 (w), 1309 (w), 1244 (w), 1198 (m), 1106 (s), 1028 (w),
996 (w), 911 (w), 737 (m), 698 (m), 648 (m), 615 (m)
MS: (ESI+, TOF)
359.2 (27), 283.2 ([M+Na]+, 15), 263.1 (17), 261.1 ([M+H]+, 26), 125.1 (21), 124.2
(45), 124.1 ([(M–CH2OCH2Ph)-CH3]+, 100), 107.1 ([OCH2Ph]+, 12), 91.1
([CH2Ph]+, 53)
HRMS: (ESI+, TOF)
calcd for C13H19Cl2O ([M+H]+): 261.0813, found: 261.0826
TLC: Rf 0.34 (98:2 hexane/EtOAc) [UV/KMnO4]
Analysis: C13H18Cl2O (261.19)
Calcd: C, 59.78; H, 6.95%
Found: C, 59.98; H, 6.73%
Preparation of tert-Butyl{[(l)-4,5-dichlorohexyl]oxy}diphenylsilane (14) (Table 3)
Following General Procedure VII, PhSeSePh (15.7 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 13 (339 mg, 1.00 mmol, 1.0 equiv) were reacted for 4 h to give an orange-red solution
which, following the work-up described in the general procedure, gave an orange oil (>99:1 dr).
Purification via flash column chromatography [42 g high porosity grade SiO2, 30 mm Ø, dry
loaded with 1.8 g SiO2, 99:1 → 98:2 → 96:4 → 95:5 petroleum ether/benzene (1.5 L, 500 mL,
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200 mL, and 200 mL, respectively), ca. 10 mL fractions then 26 g SiO2, 24 mm Ø, wet loaded,
100:0 → 99.2:0.8 hexane/Et2O (400 mL and 500 mL, respectively), ca. 10 mL fractions] gave a
clear, colourless oil (266 mg). Further purification via Kugelrohr distillation at reduced pressure
(0.05 mm Hg) gave 14 as a clear, colorless oil (262 mg, 64%).
Data for 14: bp: 171 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.69–7.66 (m, 4 H, HC(2′,2′′)), 7.46–7.37 (m, 6 H, HC(3′,3′′,4′,4′′)), 4.24 (qd, J =
6.6, 3.1 Hz, 1 H, HC(5)), 4.04 (dt, J = 9.6, 3.4 Hz, 1 H, HC(4)), 3.76–3.68 (m, 2 H,
HC(1)), 2.15–2.07 (m, 1 H, HC(3)), 1.88–1.78 (m, 2 H, HC(2,3)), 1.71–1.62 (m, 1
H, HC(2)), 1.57 (d, J = 6.7 Hz, 3 H, HC(6)), 1.07 (s, 9 H, Sit-Bu) 13C NMR: (126 MHz, CDCl3)
δ 135.6 (C(2′,2′′)), 133.79 & 133.76 (C(1′,1′′)), 129.6 (C(4′,4′′)), 127.7 (C(3′,3′′)),
66.1 (C(4)), 63.1 (C(1)), 60.0 (C(5)), 30.5 (C(3)), 29.5 (C(2)), 26.9 (SiCMe3), 20.8
(C(6)), 19.2 (SiCMe3)
IR: (neat)
3071 (w), 3050 (w), 2998 (w), 2958 (m), 2931 (m), 2895 (w), 2858 (m), 2740 (w),
1590 (w), 1472 (m), 1463 (w), 1445 (w), 1428 (m), 1389 (w), 1361 (w), 1261 (w),
1232 (w), 1111 (s), 1007 (w), 997 (w), 970 (w), 823 (m), 737 (m), 702 (m), 647 (w),
614 (m)
MS: (ESI+, TOF)
411.1 (26), 409.2 ([M+H]+, 36), 257.1 (48), 179.1 (14), 155.0 (60), 153.0 (92),
134.1 (100), 117.0 (38)
HRMS: (ESI+, TOF)
calcd for C22H31Cl2OSi ([M+H]+): 409.1521, found: 409.1519
TLC: Rf 0.33 (99:1 hexane/MTBE) [UV/KMnO4]
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Preparation of tert-Butyl{[(u)-4,5-dichlorohexyl]oxy}diphenylsilane (29i) (Table 3)
Following General Procedure VII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (241 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28i (340 mg, 1.00 mmol, 1.0 equiv) were reacted for 6 h to give a yellow-green
suspension which, following the work-up described in the general procedure, gave a yellow oil
(>99:1 dr). Purification via flash column chromatography [83 g SiO2, 34 mm Ø, dry loaded with
2.8 g SiO2, 99:1 hexane/MTBE (1.5 L), ca. 10 mL fractions] gave a pale yellow oil (≥85%
purity). Following division into two batches, further purification of each batch via flash column
chromatography {[batch I (156 mg): 42 g high porosity grade SiO2, 34 mm Ø, dry loaded with
1.8 g SiO2, 100:0 → 99:1 hexane/MTBE (2.5 L and 1.5 L, respectively), ca. 10 mL fractions]
and [batch II (176 mg): 46 g high porosity grade SiO2, 34 mm Ø, dry loaded with 2.0 g SiO2,
100:0 → 99:1 hexane/MTBE (2.5 L and 1.5 L, respectively), ca. 10 mL fractions]} gave a clear,
pale yellow oil (281 mg). Further purification via Kugelrohr distillation at reduced pressure (0.05
mm Hg) gave 29i as a clear, colorless oil (274 mg, 67%).
Data for 29i: bp: 171 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.69–7.65 (m, 4 H, HC(2′,2′′)), 7.46–7.37 (m, 6 H, HC(3′,3′′,4′,4′′)), 4.10 (app
pent, J = 6.5 Hz, 1 H, HC(5)), 3.99 (ddd, J = 9.4, 6.5, 3.0 Hz, 1 H, HC(4)), 3.75–
3.67 (m, 2 H, HC(1)), 2.21–2.14 (m, 1 H, HC(3)), 1.90–1.76 (m, 2 H, HC(2,3)),
1.72–1.65 (m, 1 H, HC(2)), 1.62 (d, J = 6.5 Hz, 3 H, HC(6)), 1.06 (s, 9 H, Sit-Bu) 13C NMR: (126 MHz, CDCl3)
δ 135.6 (C(2′,2′′)), 133.76 & 133.74 (C(1′,1′′)), 129.6 (C(4′,4′′)), 127.7 (C(3′,3′′)),
67.2 (C(4)), 63.0 (C(1)), 60.2 (C(5)), 31.7 (C(3)), 29.1 (C(2)), 26.8 (SiCMe3), 21.9
(C(6)), 19.2 (SiCMe3)
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IR: (neat)
3071 (w), 3050 (w), 2958 (m), 2931 (m), 2895 (w), 2858 (m), 2740 (w), 1590 (w),
1473 (w), 1463 (w), 1446 (w), 1428 (m), 1381 (w), 1361 (w), 1246 (w), 1195 (w),
1111 (s), 1007 (w), 998 (w), 969 (w), 823 (m), 737 (w), 702 (s), 688 (w), 650 (m),
614 (m)
MS: (ESI+, TOF)
415.3 (14), 409.2 ([M+H]+, 3), 359.2 (10), 310.3 (20), 284.3 (29), 283.3
([CH2CH2OSiPh2t-Bu]+, 23), 282.3 (100), 256.3 ([HOSiPh2t-Bu]+, 23)
HRMS: (ESI+, TOF)
calcd for C22H31Cl2OSi ([M+H]+): 409.1521, found: 409.1538
TLC: Rf 0.31 (99:1 hexane/MTBE) [UV/KMnO4]
Analysis: C22H30Cl2OSi (409.47)
Calcd: C, 64.53; H, 7.39%
Found: C, 64.68; H, 7.61%
Preparation of {[(l)-4,5-Dichloro-7-phenylheptyl]oxy}tri-iso-propylsilane (29j) and (l)-4,5-
Dichloro-7-phenylheptan-1-ol (S23) (Table 3)
Following General Procedure VII, PhSeSePh (15.7 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (241 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28j (347 mg, 1.00 mmol, 1.0 equiv) were reacted for 5 h to give a yellow-green
suspension which, following the work-up described in the general procedure, gave a yellow oil
(97:3 dr w.r.t. 29j). Partial cleavage of the tri-iso-propylsilyl group was observed; however, the
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ratio of 29j to the free alcohol dichloride S23 could not be determined by 1H NMR spectroscopy
of the crude mixture. Purification via flash column chromatography [73 g high porosity grade
SiO2, 34 mm Ø, dry loaded with 2.5 g SiO2, 100:0 → 99:1 hexane/Et2O followed by 75:25 →
60:40 hexane/EtOAc (2 L, 800 mL, 500 mL, and 400 mL, respectively), ca. 10 mL fractions]
gave 29j and S23 as pale yellow oils. Further purification of the mixed fractions, containing 29j,
[63 g high porosity grade SiO2, 34 mm Ø, dry loaded with 2.5 g SiO2, 100:0 → 99:1
hexane/MTBE (3.5 L and 1 L, respectively), ca. 10 mL fractions] gave a clear, pale yellow oil
(163 mg). Further purification via Kugelrohr distillation at reduced pressure (0.05 mm Hg) gave
29j as a clear, pale yellow oil (156 mg, 37%, contaminated with ~2% of tentatively assigned
cyclized by-products). Further purification of S23 [16 g SiO2, 18 mm Ø, wet loaded with CH2Cl2,
95:5 → 82:18 hexane/EtOAc (100 mL and 300 mL, respectively), ca. 10 mL fractions] gave a
clear, colourless oil (68.8 mg). Further purification via Kugelrohr distillation at reduced pressure
(0.05 mm Hg) gave S23 (64.9 mg, 24%) as a clear, colourless oil.
Data for 29j: bp: 163 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.34–7.28 (m, 2 H, HC(2′)), 7.24–7.18 (m, 3 H, HC(3′,4′)), 4.12 (dt, J = 9.8, 3.6
Hz, 1 H, HC(4)), 4.02 (dt, J = 9.7, 3.3 Hz, 1 H, HC(5)), 3.77–3.67 (m, 2 H, HC(1)),
2.93 (ddd, J = 13.8, 8.6, 5.2 Hz, 1 H, HC(7)), 2.74 (dt, J = 13.9, 8.2 Hz, 1 H,
HC(7)), 2.25–2.11 (m, 2 H, HC(6)), 2.11–2.02 (m, 1 H, HC(3)), 1.87 (dtd, J = 14.3,
9.7, 4.8 Hz, 1 H, HC(3)), 1.82–1.74 (m, 1 H, HC(2)), 1.67–1.58 (m, 1 H, HC(2)),
1.14–0.99 (m, 21 H, Sii-Pr3) 13C NMR: (126 MHz, CDCl3)
δ 140.5 (C(1′)), 128.53 (C(2′)), 128.50 (C(3′)), 126.2 (C(4′)), 65.5 (C(4)), 64.6
(C(5)), 62.6 (C(1)), 36.2 (C(6)), 32.7 (C(7)), 31.4 (C(3)), 29.9 (C(2)), 18.0
(SiCH(CH3)2), 12.0 (SiCH(CH3)2)
IR: (neat)
3064 (w), 3028 (w), 2943 (m), 2866 (m), 2727 (w), 1604 (w), 1497 (w), 1463 (m),
1383 (w), 1366 (w), 1235 (w), 1108 (s), 1013 (w), 996 (m), 919 (w), 882 (m), 789
(w), 732 (w), 699 (m), 681 (m), 615 (m)
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MS: (ESI+, TOF)
417.2 ([M+H]+, 11), 391.3 (13), 390.4 (33), 389.3 (94), 230.2 (23), 229.2 ([M–
CH2OSii-Pr3]+, 100), 215.0 (21), 207.1 (53)
HRMS: (ESI+, TOF)
calcd for C22H39Cl2OSi ([M+H]+): 417.2147, found: 417.2156
TLC: Rf 0.34 (99:1 hexane/MTBE) [UV/KMnO4]
Data for S23: bp: 150 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.34–7.28 (m, 2 H, HC(2′)), 7.24–7.19 (m, 3 H, HC(3′,4′)), 4.08 (dt, J = 10.0, 3.1
Hz, 1 H, HC(4)), 4.02 (dt, J = 9.9, 3.2 Hz, 1 H, HC(5)), 3.69 (tt, J = 6.0, 3.3 Hz, 2
H, HC(1)), 2.93 (ddd, J = 13.8, 8.6, 5.1 Hz, 1 H, HC(7)), 2.73 (dt, J = 13.8, 8.2 Hz,
1 H, HC(7)), 2.26–2.11 (m, 2 H, HC(6)), 2.08–2.00 (m, 1 H, HC(3)), 1.92–1.78 (m,
2 H, HC(2,3)), 1.69–1.59 (m, 1 H, HC(2)), 1.38 (br s, 1 H, OH) 13C NMR: (126 MHz, CDCl3)
δ 140.4 (C(1′)), 128.54 (C(2′)), 128.50 (C(3′)), 126.2 (C(4′)), 65.4 (C(4)), 64.5
(C(5)), 62.1 (C(1)), 36.0 (C(6)), 32.6 (C(7)), 31.1 (C(3)), 29.7 (C(2))
IR: (neat)
3577 (m), 3355 (w), 3086 (w), 3063 (w), 3027 (w), 2954 (m), 2867 (w), 1950 (w),
1873 (w), 1809 (w), 1603 (w), 1583 (w), 1497 (m), 1455 (m), 1436 (w), 1377 (w),
1288 (w), 1261 (w), 1232 (w), 1057 (m), 1030 (w), 939 (w), 909 (w), 849 (w), 751
(m), 700 (s), 648 (w), 600 (w)
MS: (ESI+, TOF)
263.1 (12), 261.1 ([M+H]+, 18), 209.1 (16), 207.1 ([M–H2O–Cl]+, 51), 189.1 ([M–
2Cl]+, 47), 173.0 (38), 171.1 (44), 171.0 ([M–2Cl–H2O]+, 100)
HRMS: (ESI+, TOF)
calcd for C13H19Cl2O ([M+H]+): 261.0813, found: 261.0820
TLC: Rf 0.27 (80:20 hexane/EtOAc) [UV/KMnO4]
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Preparation of Ethyl (l)-4,5-Dichlorohexanoate (29k) (Table 3)
Following General Procedure VII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28k (143 mg, 1.01 mmol, 1.0 equiv) were reacted for 3.5 h to give a yellow-brown
suspension which, following the work-up described in the general procedure, gave an orange oil
(>99:1 dr). Purification via flash column chromatography [77 g SiO2, 34 mm Ø, dry loaded with
2.4 g SiO2, 96:4 hexane/MTBE (1 L), ca. 10 mL fractions], followed by further purification of
the mixed fractions [24 g SiO2, 24 mm Ø, dry loaded with 1.6 g SiO2, 96:4 hexane/MTBE (500
mL), ca. 10 mL fractions], gave a pale yellow oil (176 mg). Further purification via flash column
chromatography [27 g SiO2, 24 mm Ø, wet loaded, 98:2 hexane/Et2O (600 mL), ca. 10 mL
fractions] gave a colourless oil (158 mg). Caution: the product is volatile at ca. 0.05 mm Hg.
Further purification via Kugelrohr distillation at reduced pressure (5 mm Hg) gave 29k as a clear,
colorless oil (150 mg, 70%).
Data for 29k: bp: 118 °C (ABT) (5 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 4.26 (qd, J = 6.7, 3.0 Hz, 1 H, HC(5)), 4.14 (q, J = 7.2 Hz, 2 H, CO2CH2CH3),
4.10 (dt, J = 10.7, 3.0 Hz, 1 H, HC(4)), 2.59 (ddd, J = 16.7, 7.8, 5.6 Hz, 1 H,
HC(2)), 2.54–2.45 (m, 1 H, HC(2)), 2.28 (dtd, J = 14.9, 7.8, 2.9 Hz, 1 H, HC(3)),
2.10–1.97 (m, 1 H, HC(3)), 1.59 (d, J = 6.7 Hz, 3 H, HC(6)), 1.26 (t, J = 7.1 Hz, 3
H, CO2CH2CH3) 13C NMR: (126 MHz, CDCl3)
δ 172.6 (C(1)), 65.1 (C(4)), 60.6 (CO2CH2CH3), 59.8 (C(5)), 31.1 (C(2)), 29.2
(C(3)), 20.8 (C(6)), 14.2 (CO2CH2CH3)
IR: (neat)
2983 (m), 2936 (w), 1734 (s), 1443 (m), 1378 (m), 1352 (w), 1325 (w), 1300 (w),
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1267 (m), 1187 (m), 1099 (m), 1032 (m), 994 (w), 908 (w), 857 (w), 804 (w), 691
(w), 649 (w), 603 (w)
MS: (ESI+, TOF)
284.3 (25), 282.3 (16), 256.3 (21), 252.2 (13), 215.1 (41), 213.1 ([M+H]+, 57),
181.1 (11), 179.1 (19), 177.1 ([M–Cl]+, 53), 150.0 (14), 149.0 (40), 141.1 ([M–
2Cl]+, 100), 131.0 (23), 119.1 (16), 113.1 (68), 99.1 (37)
HRMS: (ESI+, TOF)
calcd for C8H15Cl2O2 ([M+H]+): 213.0449, found: 213.0457
TLC: Rf 0.29 (96:4 hexane/EtOAc) [KMnO4]
Analysis: C8H14Cl2O2 (213.10)
Calcd: C, 45.09; H, 6.62%
Found: C, 44.96; H, 6.38%
Preparation of (l)-4,5-Dichlorohexyl Cyclopropanecarboxylate (29l) (Table 3)
Following General Procedure VII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (241 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28l (169 mg, 1.00 mmol, 1.0 equiv) were reacted for 3.5 h to give a yellow-brown
suspension which, following the work-up described in the general procedure, gave an orange oil
(>99:1 dr). Purification via flash column chromatography [66 g SiO2, 34 mm Ø, dry loaded with
2.2 g SiO2, 97:3 hexane/EtOAc (1 L), ca. 10 mL fractions] gave a pale yellow oil (174 mg).
Caution: the product is volatile at ca. 0.05 mm Hg. Further purification via Kugelrohr distillation
at reduced pressure (0.05 mm Hg) gave 29l as a clear, colorless oil (166 mg, 69%).
Data for 29l: bp: 81 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
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δ 4.26 (qd, J = 6.7, 3.0 Hz, 1 H, HC(5)), 4.17–4.07 (m, 2 H, HC(1)), 4.03 (dt, J =
10.1, 3.1 Hz, 1 H, HC(4)), 2.08–2.00 (m, 1 H, HC(3)), 2.00–1.91 (m, 1 H, HC(2)),
1.87–1.80 (m, 1 H, HC(3)), 1.80–1.71 (m, 1 H, HC(2)), 1.64–1.57 (m, 1 H, HC(8)),
1.59 (d, J = 6.7 Hz, 3 H. HC(6)), 1.01–0.97 (m, 2 H, HC(9,10)), 0.86 (dq, J = 7.6,
3.9 Hz, 2 H, HC(9,10)) 13C NMR: (126 MHz, CDCl3)
δ 174.8 (C(7)), 65.5 (C(4)), 63.5 (C(1)), 59.8 (C(5)), 30.3 (C(3)), 26.0 (C(2)), 20.6
(C(6)), 12.8 (C(8)), 8.4 (C(9,10)
IR: (neat)
3099 (w), 3016 (w), 2961 (m), 1727 (s), 1447 (m), 1404 (m), 1378 (m), 1365 (m),
1269 (m), 1235 (w), 1200 (m), 1175 (s), 1100 (w), 1077 (m), 1032 (w), 986 (w),
953 (w), 915 (w), 898 (w), 852 (w), 824 (w), 771 (w), 747 (w), 695 (w), 650 (w),
613 (w)
MS: (ESI+, TOF)
415.3 (23), 381.3 (18), 310.3 (18), 304.3 (13), 284.3 (29), 283.3 (24), 282.3 (100),
263.1 (19), 261.1 (19), 256.3 (26), 254.0 (55), 252.0 (31), 239.1 ([M+H]+, 23),
229.2 (26), 185.1 (15), 155.0 (29), 153.0 ([M–CO2CH(CH2)2]+, 43), 124.1 (30),
117.1 (15)
HRMS: (ESI+, TOF)
calcd for C10H17Cl2O2 ([M+H]+): 239.0606, found: 239.0611
TLC: Rf 0.36 (92:8 hexane/EtOAc) [KMnO4]
Analysis: C10H16Cl2O2 (239.14)
Calcd: C, 50.23; H, 6.74%
Found: C, 50.39; H, 6.70%
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Preparation of 2-Benzyl-2-[(l)-3,4-dichloropentyl]-1,3-dioxolane (29m) (Table 3)
Following General Procedure VII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (241 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28m (233 mg, 1.00 mmol, 1.0 equiv) were reacted for 3.5 h to give a yellow-brown
suspension which, following the work-up described in the general procedure, gave an orange oil
(>99:1 dr). Purification via flash column chromatography [68 g SiO2, 34 mm Ø, dry loaded with
2.2 g SiO2, 97:3 hexane/EtOAc (1.2 L), ca. 10 mL fractions] gave a pale yellow oil (226 mg).
Further purification via Kugelrohr distillation at reduced pressure (0.05 mm Hg) gave 29m as a
clear, pale yellow oil (222 mg, 73%).
Data for 29m: bp: 150 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.31–7.21 (m, 5 H, HC(2′,3′4′)), 4.23 (qd, J = 6.7, 3.0 Hz, 1 H, HC(6)), 4.02 (dt, J
= 9.9, 3.2 Hz, 1 H, HC(5)), 3.93–3.85 (m, 2 H, HC(8,9)), 3.77–3.68 (m, 2 H,
HC(8,9)), 2.93 & 2.89 (ABq, JAB = 13.8 Hz, 2 H, HC(1)), 2.13–2.04 (m, 1 H,
HC(4)), 1.94 (ddd, J = 14.6, 10.2, 4.6 Hz, 1 H, HC(3)), 1.90–1.81 (m, 1 H, HC(4)),
1.70 (ddd, J = 13.5, 10.3, 5.3 Hz, 1 H, HC(3)), 1.57 (d, J = 6.7 Hz, 3 H, HC(6)) 13C NMR: (126 MHz, CDCl3)
δ 136.4 (C(1′)), 130.5 (C(3′)), 128.0 (C(2′)), 126.5 (C(4′)), 110.8 (C(2)), 66.2 (C(5)),
65.3 & 65.2 (C(8,9), 59.9 (C(6)), 43.9 (C(1)), 34.6 (C(3)), 27.9 (C(4)), 20.6 (C(7))
IR: (neat)
3086 (w), 3062 (w), 3030 (w), 2957 (m), 2928 (m), 2886 (m), 1605 (w), 1496 (m),
1477 (m), 1455 (m), 1446 (m), 1380 (w), 1315 (w), 1266 (m), 1228 (m), 1197 (m),
1129 (m), 1078 (w), 1037 (m), 983 (w), 949 (m), 932 (w), 853 (w), 829 (w), 751
(m), 702 (m), 648 (m)
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MS: (ESI+, TOF)
305.1 (62), 304.1 (16), 303.1 ([M+H]+, 100), 261.1 (37), 259.1 (63), 225.1 ([M–
Ph]+, 13), 223.1 (46), 219.2 (35), 183.1 (12), 124.1 (20), 105.1 (10)
HRMS: (ESI+, TOF)
calcd for C15H21Cl2O2 ([M+H]+): 303.0919, found: 303.0915
TLC: Rf 0.49 (92:8 hexane/EtOAc) [UV/KMnO4]
Analysis: C15H20Cl2O2 (303.22)
Calcd: C, 59.42; H, 6.65%
Found: C, 59.66; H, 6.65%
Preparation of Methyl (l)-(E)-6,7-Dichlorooct-2-enoate (29n) (Table 3)
Following General Procedure VII, PhSeSePh (15.6 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28n (154 mg, 1.00 mmol, 1.0 equiv) were reacted for 4.5 h to give a yellow-brown
suspension which, following the work-up described in the general procedure, gave an orange oil
(99:1 dr). Purification via flash column chromatography {[74 g SiO2, 34 mm Ø, dry loaded with
2.5 g SiO2, 96:4 hexane/EtOAc (1.2 L), ca. 10 mL fractions] then [26 g SiO2, 24 mm Ø, wet
loaded with hexane, 96:4 hexane/EtOAc (500 mL), ca. 10 mL fractions]} gave a colourless oil
(162 mg). Caution: the product is volatile at ca. 0.05 mm Hg. Further purification via Kugelrohr
distillation at reduced pressure (5 mm Hg) gave 29n as a clear, colourless oil (158 mg, 70%).
Data for 29n: bp: 140 °C (ABT) (5 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 6.93 (ddd, J = 15.6, 7.6, 6.4 Hz, 1 H, HC(3)), 5.90 (dt, J = 15.7, 1.5 Hz, 1 H,
HC(2)), 4.24 (qd, J = 6.7, 3.0 Hz, 1 H, HC(7)), 3.98 (dt, J = 10.6, 3.0 Hz, 1 H,
HC(6)), 3.73 (s, 3 H, CO2CH3), 2.56–2.47 (m, 1 H, HC(4)), 2.40–2.31 (m, 1 H,
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HC(4)), 2.12–2.04 (m, 1 H, HC(5)), 1.98–1.88 (m, 1 H, HC(5)), 1.58 (d, J = 6.7 Hz,
3 H, HC(8)) 13C NMR: (126 MHz, CDCl3)
δ 166.7 (C(1)), 147.0 (C(3)), 122.2 (C(2)), 64.8 (C(6)), 59.7 (C(7)), 51.5 (CO2CH3),
31.9 (C(5)), 29.1 (C(4)), 20.5 (C8))
IR: (neat)
2985 (w), 2952 (m), 2847 (w), 1726 (s), 1660 (m), 1436 (m), 1381 (w), 1327 (w),
1314 (w), 1273 (m), 1231 (w), 1202 (m), 1161 (m), 1105 (w), 1078 (w), 1040 (w),
989 (w), 914 (w), 856 (w), 822 (w), 792 (w), 721 (w), 698 (w), 650 (w), 614 (w)
MS: (ESI+, TOF)
421.3 (38), 399.3 (29), 365.1 (13), 363.1 (19), 338.4 (14), 327.2 (21), 313.2 (38),
311.2 (92), 310.3 (18), 293.0 (23), 291.2 (27), 291.0 (31), 289.2 (61), 282.3 (100),
280.3 (15), 259.2 (21), 257.2 (45), 256.3 (25), 229.2 (30), 227.1 (54), 225.1
([M+H]+, 75), 185.1 (17), 93.1 (29)
HRMS: (ESI+, TOF)
calcd for C9H15Cl2O2 ([M+H]+): 225.0449, found: 225.0457
TLC: Rf 0.33 (92:8 hexane/EtOAc) [UV/KMnO4]
Analysis: C9H14Cl2O2 (225.11)
Calcd: C, 48.02; H, 6.27%
Found: C, 48.26; H, 6.02%
Preparation of tert-Butyl Benzyl[(u)-4,5-dichlorohexyl]carbamate (29o) (Table 3)
Following General Procedure VII, PhSeSePh (15.7 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28o (290 mg, 1.00 mmol, 1.0 equiv) were reacted for 5 h to give a yellow-brown
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suspension which, following the work-up described in the general procedure, gave a yellow oil
(99:1 dr). Purification via flash column chromatography [76 g SiO2, 34 mm Ø, dry loaded with
2.5 g SiO2, 97:3 → 96:4 hexane/EtOAc (1.2 L and 300 mL, respectively), ca. 10 mL fractions],
followed by further purification of the mixed fractions [45 g SiO2, 30 mm Ø, dry loaded with 1.5
g SiO2, 97:3 hexane/EtOAc (1 L), ca. 10 mL fractions], gave a pale yellow oil (275 mg). Further
purification via flash column chromatography [27 g SiO2, 24 mm Ø, wet loaded, 96:4
hexane/EtOAc (500 mL), ca. 10 mL fractions] gave a clear, colourless oil (263 mg). Further
purification via Kugelrohr distillation at reduced pressure (0.05 mm Hg) gave 29o as a clear,
colorless oil (258 mg, 72%).
Data for 29o: bp: 158 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, MeCN-d3, VT at 53 °C, calibrated with ethylene glycol)
δ 7.39–7.34 (m, 2 H, HC(2′)), 7.33–7.27 (m, 3 H, HC(3′,4′)), 4.49 & 4.43 (ABq,
JAB = 15.7 Hz, 2 H, HC(5′)), 4.25 (qd, J = 6.5, 5.2 Hz, 1 H, HC(5)), 4.10 (dt, J =
9.1, 3.9 Hz, 1 H, HC(4)), 3.34–3.22 (m, 2 H, HC(1)), 1.97–1.89 (m, 1 H, HC(3)),
1.87–1.78 (m, 1 H, HC(3)), 1.77–1.61 (m, 2 H, HC(2)), 1.58 (d, J = 6.6 Hz, 3 H,
HC(6)), 1.50 (s, 9 H, Ot-Bu) 13C NMR: (126 MHz, MeCN-d3, VT at 53 °C, calibrated with ethylene glycol)
δ 156.6 (NCO2t-Bu), 140.1 (C(1′)), 129.5 (C(3′)), 128.5 (C(4′)), 128.1 (C(2′)), 80.3
(NCO2CMe3), 68.4 (C(4)), 61.6 (C(5)), 51.2 (C(5′)), 47.0 (C(1)), 32.9 (C(3)), 28.92
& 28.90 (NCO2CMe3), 26.0 (C(2)), 21.84 & 21.81 (C(6))
IR: (neat)
3088 (w), 3065 (w), 3030 (w), 2977 (m), 2934 (m), 1694 (s), 1605 (w), 1586 (w),
1496 (w), 1465 (m), 1454 (m), 1416 (m), 1391 (w), 1381 (w), 1366 (m), 1308 (w),
1245 (m), 1166 (m), 1137 (m), 1176 (w), 1029 (w), 1002 (w), 969 (w), 880 (w),
769 (w), 737 (w), 700 (m), 650 (w)
MS: (ESI+, TOF)
382.2 ([M+Na]+, 11), 362.2 (13), 360.2 ([M+H]+, 21), 308.1 (14), 306.1 (72), 305.1
(18), 304.1 (100), 164.1 (12)
HRMS: (ESI+, TOF)
calcd for C18H28Cl2NO2 ([M+H]+): 360.1497, found: 360.1503
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TLC: Rf 0.24 (96:4 hexane/EtOAc) [UV/KMnO4]
Analysis: C18H27Cl2NO2 (360.32)
Calcd: C, 60.00; H, 7.55%
Found: C, 59.96; H, 7.72%
Preparation of 2-[(u)-4,5-Dichlorohexyl]isoindoline-1,3-dione (29p) (Table 3)
Following General Procedure VII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (241 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28p (231 mg, 1.01 mmol, 1.0 equiv) were reacted for 3.5 h to give a yellow-brown
suspension which, following the work-up described in the general procedure, gave a yellow oil
(97:3 dr). Purification via flash column chromatography [70 g SiO2, 34 mm Ø, dry loaded with
2.2 g SiO2, 92:8 → 90:10 hexane/EtOAc (1.2 L and 100 mL, respectively), ca. 10 mL fractions]
gave a pale yellow oil, which solidified on standing in a –20 °C freezer for ca. 1 day (239 mg).
Further purification was performed via recrystallization from boiling Et2O (2 mL), with gradual
cooling to rt and, finally, to 0 °C in a 20 mL scintillation vial loosely sealed with a screw top cap.
The crystals were collected via filtration through filter paper in a Hirsch funnel under house
vacuum, washed with (–78 °C) pentane (3 × ca. 1 mL), crushed with a spatula, and dried in
vacuo (0.05 mm Hg) overnight to give an off-white crystalline solid (138 mg). The filtrate was
concentrated in vacuo (20–23 °C, ca. 20 mm Hg) and the pale yellow solid recovered (102 mg)
was re-subjected to the same recrystallization conditions. The material from both crops was
combined to give 29p as an off-white crystalline solid (217 mg, 72%, >97:3 dr).
Data for 29p: mp: 64–65 °C (Et2O)
1H NMR: (500 MHz, CDCl3)
δ 7.87–7.82 (m, 2 H, HC(3′)), 7.75–7.69 (m, 2 H, HC(4′)), 4.07 (app pent, J = 6.5
Hz, 1 H, HC(5)), 4.02–3.95 (m, 1 H, HC(4)), 3.73 (t, J = 5.9 Hz, 2 H, HC(1)), 2.08–
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1.96 (m, 2 H, HC(2,3)), 1.88–1.77 (m, 2 H, HC(2,3)), 1.60 (d, J = 5.9 Hz, 3 H,
HC(6))
13C NMR: (126 MHz, CDCl3)
δ 168.3 (C(1′)), 134.0 (C(4′)), 132.0 (C(2′)), 123.3 (C(3′)), 66.3 (C(4)), 60.0 (C(5)),
37.1 (C(1)), 32.1 (C(3)), 25.4 (C(2)), 22.0 (C(6))
IR: (neat)
2935 (w), 2873(w), 1771 (m), 1716 (s), 1615 (w), 1465 (w), 1456 (w), 1436 (w),
1397 (m), 1366 (w), 1331 (w), 1257 (w), 1220 (w), 1203 (w), 1186 (w), 1088 (w),
1061 (w), 1045 (w), 1021 (m), 988 (w), 887 (w), 835 (w), 801 (w), 750 (w), 720
(m), 713 (m), 648 (m),
MS: (ESI+, TOF)
304.1 (14), 302.1 (72), 300.1 ([M+H]+, 100), 282.3 (12), 264.1 ([M–Cl]+, 19), 228.1
([M–2Cl]+, 36), 160.1 ([C9H6NO2]+, 13)
HRMS: (ESI+, TOF)
calcd for C14H16Cl2NO2 ([M+H]+): 300.0558, found: 300.0558
TLC: Rf 0.22 (92:8 hexane/EtOAc) [UV/KMnO4]
Analysis: C14H15Cl2NO2 (300.18)
Calcd: C, 56.02; H, 5.04%
Found: C, 56.13; H, 4.97%
Preparation of tert-Butyl{[(l)-2,3-dichlorohexyl]oxy}diphenylsilane (29q) (Table 3)
Following General Procedure VII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28q (340 mg, 1.00 mmol, 1.0 equiv) were reacted for 7 h to give a red-brown suspension
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which, following the work-up described in the general procedure, gave a yellow oil (>99:1 dr).
Purification via flash column chromatography [42 g high porosity grade SiO2, 30 mm Ø, dry
loaded with 1.5 g SiO2, 99:1 petroleum ether/benzene (900 mL), ca. 10 mL fractions], followed
by further purification of the mixed fractions [46 g high porosity grade SiO2, 34 mm Ø, dry
loaded with 1.8 g SiO2, hexane (1.5 L), ca. 10 mL fractions], gave a colourless oil (287 mg).
Further purification via Kugelrohr distillation at reduced pressure (0.05 mm Hg) gave 29q as a
clear, colorless oil (280 mg, 71%, contaminated with 4% vinylic chloride by-product). The 1H
and 13C NMR spectroscopic data matched that for alternative preparations.27
Data for 29q: bp: 171 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.70–7.64 (m, 4 H, HC(2′,2′′)), 7.48–7.38 (m, 6 H, HC(3′,3′′,4′4′′)), 4.47 (ddd, J =
9.0, 5.2, 2.1 Hz, 1 H, HC(3)), 4.07 (ddd, J = 7.8, 5.5, 2.2 Hz, 1 H, HC(2)), 3.98 (dd,
J = 10.3, 8.2 Hz, 1 H, HC(1)), 3.84 (dd, J = 10.3, 5.5 Hz, 1 H, HC(1)), 1.92 (ddt, J
= 14.3, 9.3, 4.7 Hz, 1 H, HC(4)), 1.86–1.77 (m, 1 H, HC(4)), 1.63–1.52 (m, 1 H,
HC(5)), 1.52–1.41 (m, 1 H, HC(5)), 1.07 (s, 9 H, Sit-Bu), 0.97 (t, J = 7.4 Hz, 3 H,
HC(6)) 13C NMR: (126 MHz, CDCl3)
δ 135.6 & 135.5 (C(2′,2′′)), 133.0 & 132.8 (C(1′,1′′)), 129.9 (C(4′,4′′)), 127.82 &
127.80 (C(3′,3′′)), 64.9 (C(2)), 63.7 (C(1)), 61.2 (C(3)), 37.6 (C(4)), 26.8 (SiCMe3),
19.8 (SiCMe3), 19.2 (C(5)), 13.4 (C(6))
IR: (neat)
3072 (w), 3051 (w), 2999 (w), 2960 (m), 2933 (m), 2859 (m), 1590 (w), 1488 (w),
1472 (m), 1428 (m), 1391 (w), 1362 (w), 1274 (w), 1258 (w), 1189 (w), 1113 (s),
1008 (w), 999 (w), 937 (w), 920 (w), 881 (w), 824 (m), 760 (w), 740 (m), 702 (s),
650 (w), 613 (m)
MS: (ESI+ TOF)
431.1 ([M+Na]+, 10), 421.2 (15), 413.3 (48), 399.2 (17), 377.2 (11), 360.2 (20),
359.2 (100), 348.3 (10), 283.2 (37), 282.3 (28), 256.8 (16), 149.0 (14), 125.1 (10),
124.1 (91)
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HRMS: (ESI+ TOF)
calcd for C22H31Cl2OSi ([M+H]+): 409.1521, found: 409.1516
TLC: Rf 0.53 (MTBE/hexanes, 1%) [UV/KMnO4]
Preparation of tert-Butyl{[(u)-2,3-dichlorohexyl]oxy}diphenylsilane (29r) (Table 3)
Following General Procedure VII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (241 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28r (340 mg, 1.01 mmol, 1.0 equiv) were reacted for 9 h to give a yellow-brown
suspension which, following the work-up described in the general procedure, gave an orange oil
(99:1 dr). Purification via flash column chromatography [41 g high porosity grade SiO2, 30 mm
Ø, dry loaded with 1.5 g SiO2, 100:0 → 98:2 → 95:5 petroleum ether/Et2O (700 mL, 200 mL,
and 100 mL, respectively), ca. 10 mL fractions] gave a colourless oil (266 mg). Further
purification via Kugelrohr distillation at reduced pressure (0.05 mm Hg) gave 29r as a clear,
colorless oil (260 mg, 67%, >99:1 dr, contaminated with 1% vinylic chloride by-product). The 1H and 13C NMR spectroscopic data matched that for alternative preparations.27
Data for 29r: bp: 171 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.72–7.68 (m, 4 H, HC(2′,2′′)), 7.48–7.38 (m, 6 H, HC(3′,3′′,4′4′′)), 4.36 (ddd, J =
9.4, 6.3, 2.8 Hz, 1 H, HC(3)), 4.11–4.06 (m, 2 H, HC(1,2)), 3.91 (dd, J = 12.5, 6.5
Hz, 1 H, HC(1)), 1.94 (dddd, J = 12.8, 9.1, 6.2, 2.7 Hz, 1 H, HC(4)), 1.82–1.74 (m,
1 H, HC(4)), 1.72–1.83 (m, 1 H, HC(5)), 1.51–1.40 (m, 1 H, HC(5)), 1.08 (s, 9 H,
Sit-Bu), 0.96 (t, J = 7.4 Hz, 3 H, HC(6)) 13C NMR: (126 MHz, CDCl3)
δ 135.61 & 135.57 (C(2′,2′′)), 132.85 & 132.82 (C(1′,1′′)), 129.9 (C(4′,4′′)), 127.8
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(C(3′,3′′)), 65.2 (C(2)), 65.1 (C(1)), 61.7 (C(3)), 35.9 (C(4)), 26.7 (SiCMe3), 19.3
(SiCMe3), 19.2 (C(5)), 13.5 (C(6))
IR: (neat)
2985 (w), 2952 (m), 2847 (w), 1726 (s), 1660 (m), 1436 (m), 1381 (w), 1327 (w),
1314 (w), 1273 (m), 1231 (w), 1202 (m), 1161 (m), 1105 (w), 1178 (w), 1040 (w),
989 (w), 914 (w), 856 (w), 922 (w), 792 (w), 721 (w), 698 (w), 650 (w), 614 (w)
MS: (ESI+ TOF)
414.3 (29), 413.3 (100), 409.3 ([M+H]+, 2), 392.3 (10), 391.3 (35). 339.3 (10),
338.3 (36), 279.2 (24), 167.0 (25), 149.0 (37), 113.1 (25)
HRMS: (ESI+ TOF)
calcd for C22H31Cl2OSi ([M+H]+): 409.1521, found: 409.1522
TLC: Rf 0.56 (MTBE/hexanes, 1%) [UV/KMnO4]
Preparation of tert-Butyl{[(l)-2,3-dichloro-5-phenylpentyl]oxy}dimethylsilane (29s) and (l)-
2,3-Dichloro-5-phenylpentan-1-ol (29u) (Table 3)
Following General Procedure VII, PhSeSePh (15.6 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), 23 (126
mg, 115 µL, 1.02 mmol, 1.0 equiv), Me3SiCl (218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and
alkene 28s (277 mg, 1.00 mmol, 1.0 equiv) were reacted for 6 h to give a yellow-brown
suspension which, following the work-up described in the general procedure, gave a yellow oil
(>98:2 dr w.r.t. sum of 29s and the free alcohol dichloride 29u). Partial cleavage of the tert-
butyldimethylsilyl group was observed by 1H NMR spectroscopy of the crude mixture as a 2.3:1
mixture of 29s:29u. Purification via flash column chromatography [72 g SiO2, 34 mm Ø, dry
loaded with 2.5 g SiO2, 100:0 → 99.2:0.8 hexane/Et2O followed by 88:12 hexane/EtOAc (1 L, 1
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L, and 1.1 L, respectively), ca. 10 mL fractions] gave 29s and 29u as pale yellow oils. Further
purification of the mixed fractions, containing 29s, via flash column chromatography [53 g high
porosity grade SiO2, 34 mm Ø, dry loaded with 2.2 g SiO2, 100:0 → 98:8:1.2 hexane/MTBE (2 L
and 500 mL, respectively), ca. 10 mL fractions then 25 g SiO2, 24 mm Ø, wet loaded, 100:0 →
95.5:0.5 → 99:1 hexane:Et2O (400 mL, 200 mL, and 200 mL, respectively), ca. 10 mL fractions]
gave a colourless oil (166 mg). Further purification via Kugelrohr distillation at reduced pressure
(0.05 mm Hg) gave 29s as a clear, colourless oil (163 mg, 47%). Further purification of 29u via
flash column chromatography [26 g SiO2, 24 mm Ø, wet loaded with CH2Cl2, 96:4 → 88:12
hexane/EtOAc (100 mL and 500 mL, respectively), ca. 10 mL fractions] gave 29u as a clear,
colourless oil (49.9 mg, 21%, contaminated with 3% vinylic chloride by-product). The 1H and 13C NMR spectroscopic data matched that for the catalytic syn-dichlorination of allylic alcohol
28u (vide infra).
Data for 29s: bp: 118 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.32–7.27 (m, 2 H, HC(2′)), 7.24–7.18 (m, 3 H, HC(3′,4′)), 4.29 (ddd, J = 9.9, 4.0,
2.0 Hz, 1 H, HC(3)), 4.01 (ddd, J = 7.5, 5.4, 2.0 Hz, 1 H, HC(2)), 3.87 (dd, J = 10.0,
8.6 Hz, 1 H, HC(1)), 3.78 (dd, J = 10.0, 5.4 Hz, 1 H, HC(1)), 2.90 (ddd, J = 13.6,
8.3, 5.2 Hz, 1 H, HC(5)), 2.77 (dt, J = 13.9, 8.1 Hz, 1 H, HC(5)), 2.34–2.24 (m, 1 H,
HC(4)), 2.09 (ddd, J = 18.2, 8.2, 4.0 Hz, 1 H, HC(4)), 0.84 (s, 9 H, Sit-Bu), 0.05 (s,
6 H, SiMe2) 13C NMR: (126 MHz, CDCl3)
δ 140.4 (C(1′)), 128.54 & 128.52 (C(2′,3′)), 126.2 (C(4′)), 64.3 (C(1)), 64.0 (C(2)),
60.4 (C(3)), 37.4 (C(4)), 32.5 (C(5)), 25.7 (SiCMe3), 18.1 (SiCMe3), –5.45 & –5.52
(SiMe2)
IR: (neat)
3087 (w), 3065 (w), 3028 (w), 2955 (m), 2929 (m), 2884 (w), 2857 (m), 1604 (w),
1497 (w), 1471 (m), 1463 (m), 1455 (m), 1433 (w), 1407 (w), 1390 (w), 1362 (w),
1258 (m), 1120 (s), 1006 (w), 996 (w), 939 (w), 838 (m), 815 (w), 779 (m), 749 (w),
699 (m), 667 (w), 624 (w), 615 (w)
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MS: (ESI+, TOF)
437.2 (18), 416.2 (29), 415.2 (100), 399.3 (56), 390.2 (13), 362.2 (11), 356.2 (15),
349.2 (25), 347.2 ([M+H]+, 35), 282.3 (24), 275.2 (13), 179.1 (21), 156.1 (11),
143.1 (23), 119.1 (44)
HRMS: (ESI+, TOF)
calcd for C17H29Cl2OSi ([M+H]+): 347.1365, found: 347.1378
TLC: Rf 0.42 (99:1 hexane/MTBE) [UV/KMnO4]
Analysis: C17H28Cl2OSi (347.39)
Calcd: C, 58.78; H, 8.12%
Found: C, 59.07; H, 7.73%
General Procedure VIII: Catalytic, syn-Dichlorination of Allylic Alcohols (Table 3)
An oven-dried, 10-mL Schlenk flask equipped with a magnetic stirrer bar was taken into
the glovebox and charged sequentially with diphenyl diselenide (PhSeSePh) (15.8 mg, 0.05
mmol, 5 mol %), benzyltriethylammonium chloride (BnEt3NCl) (690 mg, 3.03 mmol, 3.0 equiv),
and N-fluoropyridinium tetrafluoroborate 11 (240 mg, 1.30 mmol, 1.3 equiv), and was then
sealed with a rubber septum, removed from the box, and placed under argon. MeCN (5.0 mL)
and chlorotrimethylsilane (Me3SiCl) (218 mg, 255 µL, 2.01 mmol, 2.0 equiv) were then added
sequentially and stirring was commenced. After ca. 10 min, an off-white suspension
(occasionally with yellow tinges) was observed. At this point, the requisite allylic alcohol (1.00
mmol, 1.0 equiv) was transferred via syringe to the reaction mixture [for allylic alcohols of
unknown density, only 3.0 mL of MeCN was added initially and the remaining 2.0 mL (in two
1.0 mL portions) was used to transfer the allylic alcohol across from an oven-dried, 4-mL dram
vial under an argon atmosphere, via syringe]. The resultant suspension was stirred at rt, and was
monitored by TLC until no allylic alcohol substrate could be detected. Once the reaction had
reached completion, sat. aq. NaHCO3 (1.0 mL) was added to quench any unreacted
chlorotrimethylsilane. After stirring for ca. 10 min at rt, the resultant mixture was transferred to a
separatory funnel and diluted with H2O (15 mL). The aqueous layer was extracted with Et2O (3 ×
15 mL), and the combined organic extracts were washed with brine (15 mL), then dried (MgSO4),
filtered, and concentrated in vacuo (20–23 °C, ca. 20 mm Hg). The resultant residue was re-
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dissolved in EtOAc/Et2O (1:1 v/v, 5 mL) and eluted through a short plug of silica gel (ca. 0.55 g
SiO2 packed into a Pasteur pipet to a height of ca. 40 mm) to remove any ammonium salts, and
the plug was rinsed through with further portions of Et2O (3 × 5 mL) The solvent was removed
in vacuo (20–23 °C, ca. 20 mm Hg for non-volatile products or 5–8 °C, ca. 20 mm Hg for
volatile products), and an aliquot of the crude mixture was dissolved in CDCl3 to measure the
syn/anti diastereoisomeric ratio (dr) by 1H NMR spectroscopy. The syn-dichloride product was
then isolated as described.
Preparation of (l)-2,3-Dichlorohexan-1-ol (29t) (Table 3)
Following General Procedure VIII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (241 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), Me3SiCl
(218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and (E)-2-hexen-1-ol 28t (102 mg, 120 µL, 1.02 mmol,
1.0 equiv) were reacted for 14 h to give a clear, light yellow solution which, following the work-
up described in the general procedure, gave a yellow oil (99:1 dr). Purification via flash column
chromatography [26 g SiO2, 24 mm Ø, dry loaded with 1.2 g SiO2, 95:5 → 84:16 hexane/Et2O
(100 mL and 500 mL, respectively), ca. 10 mL fractions then 22 g SiO2, 24 mm Ø, wet loaded,
98:2 → 90:10 hexane/EtOAc (100 mL and 500 mL, respectively), ca. 10 mL fractions] gave a
clear, slightly yellow oil (113 mg). Caution: the product is volatile at ca. 0.05 mm Hg. Further
purification via Kugelrohr distillation at reduced pressure (5 mm Hg) gave 29t as a clear,
colorless oil (109 mg, 66%).
Data for 29t: bp: 100 °C (ABT) (5 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 4.24 (ddd, J = 8.4, 6.0, 2.7 Hz, 1 H, HC(3)), 4.16 (td, J = 6.4, 2.7 Hz, 1 H, HC(2)),
3.95 (dt, J = 12.8, 6.6 Hz, 1 H, HC(1)), 3.92–3.85 (m, 1 H, HC(1)), 2.15–2.04 (m, 1
H, OH), 1.92–1.80 (m, 2 H, HC(4)), 1.65–1.53 (m, 1 H, HC(5)), 1.50–1.38 (m, 1 H,
HC(5)), 0.96 (t, J = 7.4 Hz, 3 H, HC(6))
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13C NMR: (126 MHz, CDCl3)
δ 65.4 (C(2)), 64.5 (C(1)), 61.7 (C(3)), 37.2 (C(4)), 19.8 (C(5)), 13.4 (C(6))
IR: (neat)
3363 (m), 2962 (m), 2937 (m), 2876 (m), 1634 (w), 1465 (m), 1434 (w), 1383 (w),
1274 (w), 1135 (s), 1058 (m), 997 (w), 915 (w), 881 (w), 843 (w), 771 (w), 756 (w),
732 (w), 615 (m)
MS: (CI+, DFSF)
173.0 (12), 171.0 ([M+H]+, 18), 155.0 (18), 153.0 ([M–OH]+, 21), 119.0 (39), 117.0
([(M–HCl)–OH]+, 75), 106.0 (34), 104.0 (70), 99.1 (48), 91.0 (20), 89.0 (24), 81.1
({[(M–HCl)–OH]-HCl}+, 100), 75.0 (24), 69.1 (40), 68.1 (42), 57.1 (34), 55.1 (61)
HRMS: (CI+, DFSF)
calcd for C6H13Cl2O ([M+H]+): 171.03436, found: 171.03426
TLC: Rf 0.44 (80:20 hexane/EtOAc) [KMnO4]
Analysis: C6H12Cl2O (171.06)
Calcd: C, 42.13; H, 7.07%
Found: C, 42.13; H, 7.02%
Preparation of (l)-2,3-Dichloro-5-phenylpentan-1-ol (29u) (Table 3)
Following General Procedure VIII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), Me3SiCl
(218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and allylic alcohol 28u (162 mg, 1.00 mmol, 1.0 equiv)
were reacted for 9 h to give a clear, light yellow solution which, following the work-up described
in the general procedure, gave an orange oil (98:2 dr). Purification via flash column
chromatography [76 g SiO2, 34 mm Ø, dry loaded with 2.5 g SiO2, 95:5 → 85:15 hexane/EtOAc
(500 mL and 1 L, respectively), ca. 10 mL fractions then 72 g high porosity grade SiO2, 34 mm
Ø, wet loaded with CH2Cl2, 100:0 (not collected) → 91:9 hexane/acetone (100 mL and 800 mL,
respectively), ca. 10 mL fractions] gave 29u as a clear, colourless oil (173 mg, 76%). The
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product 29u was obtained in three different fractions, each being contaminated with ≤6.5% of the
vinylic chloride by-product, (E)-3-chloro-5-phenylpent-2-en-1-ol: fraction I (T50–52, 51 mg,
93.5% purity), fraction II (T53–63, 83 mg, 97.5% purity), and fraction III (T64–82, 39 mg, 99%
purity).
Data for 29u (from fraction III): bp: 127 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.35–7.29 (m, 2 H, HC(2′)), 7.25–7.20 (m, 3 H, HC(3′,4′)), 4.21–4.13 (m, 2 H,
HC(2,3)), 3.97–3.84 (m, 2 H, HC(1)), 2.93 (ddd, J = 13.8, 8.6, 5.2 Hz, 1 H, HC(5)),
2.76 (dt, J = 13.9, 8.2 Hz, 1 H, HC(5)), 2.28–2.13 (m, 2 H, HC(4)), 2.05 (dd, J =
7.5, 5.3 Hz, 1 H, OH) 13C NMR: (126 MHz, CDCl3)
δ 140.2 (C(1′)), 128.6 & 128.5 (C(2′,3′)), 126.3 (C(4′)), 65.4 (C(2)), 64.4 (C(1)),
61.0 (C(3)), 36.8 (C(4)), 32.5 (C(5))
IR: (neat)
3554 (w), 3385 (m), 3086 (w), 3063 (w), 3027 (m), 2939 (m), 2863 (w), 1949 (w),
1875 (w), 1808 (w), 1603 (w), 1583 (w), 1496 (m), 1455 (m), 1432 (w), 1285 (w),
1267 (w), 1135 (m), 1101 (m), 1079 (m), 1031 (m), 996 (w), 910 (w), 840 (w), 782
(w), 751 (m), 700 (m), 623 (m)
MS: (EI+, TOF)
234.0 (17), 232.0 (M+, 27), 197.1 ([M–Cl]+, 10), 160.1 (10), 143.1 (64), 129.1 (26),
128.1 (19), 125.1 (16), 117.1 (22), 115.1 (16), 105.1 (23), 104.1 (48), 92.1 (18),
91.0 ([CH2Ph]+, 100), 65.0 (13)
HRMS: (EI+, TOF)
calcd for C11H14Cl2O (M+): 232.0422, found: 232.0427
TLC: 29u – Rf 0.38 (80:20 hexane/EtOAc) [UV/KMnO4]
vinylic chloride – Rf 0.32 (80:20 hexane/EtOAc) [UV/KMnO4]
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Preparation of (u)-2,3-Dichloro-5-phenylpentan-1-ol (29v) (Table 3)
Following General Procedure VIII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), Me3SiCl
(218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and allylic alcohol 28v (163 mg, 1.00 mmol, 1.0 equiv)
were reacted for 9 h to give a clear, light yellow solution which, following the work-up described
in the general procedure, gave an orange oil (98:2 dr). Purification via flash column
chromatography [73 g SiO2, 34 mm Ø, dry loaded with 2.4 g SiO2, 96:4 → 88:12 hexane/EtOAc
(500 mL and 1.1 L, respectively), ca. 10 mL fractions then 74 g high porosity grade SiO2, 34 mm
Ø, wet loaded with CH2Cl2, 100:0 (not collected) → 96:4 (not collected) → 88:12 hexane/EtOAc
(100 mL, 100 mL, and 1 L, respectively), ca. 10 mL fractions] gave 29v as a clear, pale yellow
oil (166 mg, 71%). The product 29v was obtained in two different fractions, in which fraction II
was contaminated with the vinylic chloride by-product, (Z)-3-chloro-5-phenylpent-2-en-1-ol:
fraction I (T54–69, 136 mg), fraction II (T70–86, 30 mg, ca. 89% purity). Further purification of
29v from fraction I via Kugelrohr distillation at reduced pressure (0.05 mm Hg) gave a clear,
colorless oil (134 mg, 98.5% mass return).
Data for 29v (from fraction I): bp: 130 °C (ABT) (0.05 mm Hg)
1H NMR: (500 MHz, CDCl3)
δ 7.35–7.28 (m, 2 H, HC(2′)), 7.25–7.18 (m, 3 H, HC(3′,4′)), 4.13–4.06 (m, 2 H,
HC(2,3)), 4.01 (dd, J = 6.9, 3.7 Hz, 2 H, HC(1)), 2.96 (ddd, J = 13.9, 9.6, 4.6 Hz, 1
H, HC(5)), 2.77 (ddd, J = 13.7, 9.2, 7.4 Hz, 1 H, HC(5)), 2.47–2.38 (m, 1 H,
HC(4)), 2.14–2.04 (m, 1 H, HC(4)), 1.95 (t, J = 7.0 Hz, 1 H, OH) 13C NMR: (126 MHz, CDCl3)
δ 140.4 (C(1′)), 128.6 & 128.5 (C(2′,3′)), 126.3 (C(4′)), 66.3 (C(2)), 64.5 (C(1)),
60.8 (C(3)), 36.7 (C(4)), 31.8 (C(5))
IR: (neat)
3564 (w), 3390 (m), 3086 (w), 3063 (m), 3028 (w), 2931 (m), 2882 (w), 1948 (w),
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1603 (w), 1497 (m), 1455 (m), 1433 (w), 1385 (w), 1240 (w), 1196 (w), 1105 (w),
1065 (m), 1030 (w), 966 (w), 908 (w), 839 (w), 775 (w), 750 (m), 700 (m), 655 (m)
MS: (EI+, TOF)
234.0 (19), 232.0 (M+, 33), 160.1 (11), 143.1 (66), 129.1 (28), 128.1 (21), 125.1
(20), 117.1 (28), 115.1 (18), 105.1 (21), 104.1 (57), 103.1 (11), 92.1 (29), 91.0
([CH2Ph]+, 100), 77.0 ([C6H5]+, 15), 65.0 (28)
HRMS: (EI+, TOF)
calcd for C11H14Cl2O (M+): 232.0422, found: 232.0425
TLC: Rf 0.40 (80:20 hexane/EtOAc) [UV/KMnO4]
Preparation of 4-(Benzyloxy)-(l)-2,3-dichlorobutan-1-ol (29w) and 4-(Benzyloxy)-(u)-2,3-
dichlorobutan-1-ol (29x) (Table 3)
Following General Procedure VIII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (241 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), Me3SiCl
(218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and allylic alcohol 28w (179 mg, 1.00 mmol, 1.0
equiv) were reacted for 47 h to give a light yellow solution with tinges of cloudiness. TLC
analysis showed that a trace amount of 28w remained. Following the work-up described in the
general procedure, an orange oil was obtained (56:44 29w:29x). (Note: 29w and its
diastereoisomeric dichloride 29x were inseparable on TLC despite numerous attempts with
different solvent systems). Purification via flash column chromatography [41 g high porosity
grade SiO2, 30 mm Ø, dry loaded with 1.5 g SiO2, 95:5 → 80:20 → 75:25 petroleum ether/Et2O
(120 mL, 1 L, and 200 mL, respectively), ca. 10 mL fractions then 28 g SiO2, 24 mm Ø, wet
loaded with CH2Cl2, 96:4 → 88:12 hexane/EtOAc (100 mL and 600 mL, respectively), ca. 10
mL fractions] gave a 56:44 mixture of 29w:29x as a clear, colourless, viscous oil (168 mg, 67%
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combined, contaminated with 3% of an unidentified benzyloxy-containing impurity). The 1H and 13C NMR spectroscopic data of 29w matched that for alternative preparations.27,29
Data for mixture of 29w and 29x:
1H NMR: (500 MHz, CDCl3)
δ 7.40–7.29 (m, 5 H, HC(2′,3′,4′), 29w & 29x), 4.64 & 4.60 (ABq, JAB = 12.0 Hz, 2
H, HC(5′), 29x), 4.59 (s, 2 H, HC(5′), 29w), 4.45–4.37 (m, 2 H, HC(2′,3′), 29w),
4.36 (dt, J = 8.2, 4.3 Hz, 1 H, HC(2), 29x), 4.30 (dt, J = 8.0, 4.1 Hz, 1 H, HC(3),
29x), 4.07–3.96 (m, 2 H, HC(1), 29x), 3.95–3.84 (m, 2 H each for both 29w & 29x,
HC(1) for 29w, HC(4) for 29x), 3.83–3.75 (m, 2 H, HC(4), 29w), 2.26 (t, J = 7.0
Hz, 1 H, OH, 29x), 2.21 (dd, J = 7.7, 5.4 Hz, 1 H, OH, 29w) 13C NMR: (126 MHz, CDCl3)
δ 137.3 (C(1′), 29x), 137.2 (C(1′), 29w), 128.51 (C(3′), 29w), 128.47 (C(3′), 29x),
128.0 (C(4′), 29w), 127.9 (C(4′), 29x), 127.8 (C(2′), 29w), 127.7 (C(2′), 29x), 73.6,
(C(5′), 29w & 29x), 70.8 (C(4), 29x), 70.6 (C(4), 29w), 64.1 (C(1), 29w & 29x),
62.9 (C(2), 29x), 61.9 (C(2), 29w), 59.3 (C(3), 29x), 58.4 (C(3), 29w)
IR: (neat)
3404 (m), 3088 (w), 3064 (w), 3031 (w), 2936 (w), 2872 (m), 1604 (w), 1497 (w),
1455 (m), 1364 (m), 1310 (w), 1251 (w), 1207 (w), 1077 (m), 1029 (m), 911 (w),
861 (w), 790 (w), 740 (m), 698 (m), 665 (w), 607 (w)
MS: (ESI+, TOF)
342.0 (17), 341.0 (17), 303.0 (14), 251.1 (65), 250.1 (14), 249.1 ([M+H]+, 100),
158.0 (17), 130.0 (13), 91.1 ([CH2Ph]+, 91)
HRMS: (ESI+, TOF)
calcd for C11H15Cl2O2 ([M+H]+): 249.0449, found: 249.0450
TLC: Rf 0.34 (80:20 hexane/EtOAc) [UV/KMnO4]
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Preparation of 4-(Benzyloxy)-(u)-2,3-dichlorobutan-1-ol (29x) (Table 3)
Following General Procedure VIII, PhSeSePh (15.8 mg, 0.05 mmol, 5 mol %), BnEt3NCl
(690 mg, 3.03 mmol, 3.0 equiv), 11 (240 mg, 1.30 mmol, 1.3 equiv), MeCN (5.0 mL), Me3SiCl
(218 mg, 255 µL, 2.01 mmol, 2.0 equiv), and allylic alcohol 28x (179 mg, 1.00 mmol, 1.0 equiv)
were reacted for 15 h to give a clear, light yellow solution which, following the work-up
described in the general procedure, gave a yellow oil (93:7 dr). Purification via flash column
chromatography [24 g SiO2, 24 mm Ø, dry loaded with 1.2 g SiO2, 95:5 → 82:18 hexane/EtOAc
(100 mL and 400 mL, respectively), ca. 10 mL fractions], followed by further purification of the
mixed fractions [23 g SiO2, 24 mm Ø, dry loaded with 1.2 g SiO2, 96:4 → 88:12 hexane/EtOAc
(100 mL and 500 mL, respectively), ca. 10 mL fractions], gave 29x as a clear, colorless oil,
which solidified to a white solid on standing in a –20 °C freezer for ca. 1 day (181 mg, 73%,
96:4 dr). Further purification was performed via recrystallization from boiling Et2O (2 mL), with
gradual cooling to rt and, finally, to 0 °C in a 20 mL scintillation vial loosely sealed with a screw
top cap. The crystals were collected via filtration through filter paper in a Hirsch funnel under
house vacuum, washed with (–78 °C) hexane (3 × ca. 1 mL), crushed with a spatula, and dried in
vacuo (0.05 mm Hg) overnight to give a white, crystalline solid (138 mg). The filtrate was
concentrated in vacuo (20–23 °C, ca. 20 mm Hg) and the white solid recovered (52 mg) was re-
subjected to the same recrystallization conditions. The material from both crops was combined to
give 29x as a white, crystalline solid (170 mg, 94% mass return, 97:3 dr). The 1H and 13C NMR
spectroscopic data matched that for alternative preparations.27,29
Data for 29x: mp: 44–46 °C (Et2O) [lit: 36–40 °C (hexane/Et2O)]27
1H NMR: (500 MHz, CDCl3)
δ 7.40–7.29 (m, 5 H, HC(2′,3′,4′)), 4.64 & 4.60 (ABq, JAB = 12.0 Hz, 2 H, HC(5′)),
4.36 (dt, J = 8.2, 4.3 Hz, 1 H, HC(2)), 4.30 (dt, J = 8.0, 4.1 Hz, 1 H, HC(3)), 4.07–
3.96 (m, 2 H, HC(1)), 3.95–3.84 (m, 2 H, HC(4)), 2.21 (t, J = 7.0 Hz, 1 H, OH)
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13C NMR: (126 MHz, CDCl3)
δ 137.3 (C(1′)), 128.47 (C(3′)), 127.9 (C(4′)), 127.7 (C(2′)), 73.6, (C(5′)), 70.8
(C(4)), 64.1 (C(1)), 62.9 (C(2)), 59.3 (C(3))
IR: (neat)
3361 (m), 3267 (m), 3065 (w), 3029 (w), 2937 (w), 2909 (w), 2872 (w), 1605 (w),
1495 (w), 1451 (w), 1404 (w), 1359 (m), 1308 (w), 1288 (w), 1238 (w), 1194 (w),
1140 (w), 1111 (w), 1086 (m), 1077 (w), 1044 (w), 1027 (w), 1003 (w), 931 (w),
731 (s), 694 (m), 655 (m)
MS: (ESI+, TOF)
271.0 ([M+Na]+, 10), 251.1 (52), 249.1 ([M+H]+, 76), 125.1 (15), 124.2 (24), 124.1
({[M–(OCH2Ph)]–OH}+, 100), 91.1 ([CH2Ph]+, 66)
HRMS: (ESI+, TOF)
calcd for C11H15Cl2O2 ([M+H]+): 249.0449, found: 249.0454
TLC: Rf 0.31 (80:20 hexane/EtOAc) [UV/KMnO4]
Determination of Relative Configurations within Dichlorides (Table 3)
The relative configurations within the dichlorides prepared via catalytic syn-
dichlorination (Table 3) were determined as follows:
1. The relative configuration within dichloride 7 was assigned as syn by comparing the 1H
NMR spectroscopic data to that from a commercial sample of its diastereoisomeric
dichloride trans-1,2-dichlorocyclohexane (Aldrich, 99%) (all measurements in CDCl3).
2. The relative configurations within dichlorides 29q,r,w,x were assigned as syn by
comparing the 1H and 13C NMR spectroscopic data to those from known dichlorides (all
measurements in CDCl3).27,29
3. The relative configurations within dichlorides 29t-v were assigned as syn by comparing
the 1H chemical shifts for HC(1,2,3) within the dichlorides to those from the analogous
anti-dichloride (u)-2,3-dichloro-1-nonanol (all measurements in CDCl3).30
4. The relative configurations in syn-configured dichlorides 18, 14, 29j-n were assigned by
comparison of the vicinal dichloride 1H-1H 3J coupling constants of 3.0–3.3 Hz to that
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measured for the known syn-dichloride (l)-2,3-dichlorooctane,28 which is also 3.0 Hz (all
measurements in CDCl3).
5. An authentic sample of the anti-configured dichloride 29i was prepared via an anti-
selective dichlorination of the (E)-alkene 13 with Cl2 (NMR experiment), and its1H NMR
data matched that for its preparation via a catalytic syn-dichlorination of the (Z)-alkene
28i. The measured vicinal dichloride 1H-1H 3J coupling constant of 6.5 Hz for 29i
contrasts with the value of ca. 3 Hz measured for its diastereoisomer 14. A similar
observation was made with the syn-configured dichloride 29j (3JHH = 3.2 Hz) and its
diastereoisomeric dichloride (3JHH = 6.3 Hz). Thus, the relative configurations within
anti-configured dichlorides 29h,p,o were all assigned based on measured vicinal chloride 1H-1H 3J coupling constants of 6.5–6.6 Hz (all measurements in CDCl3).
6. The relative configuration within dichloride 29s was assigned as syn by comparison of
the vicinal dichloride 1H-1H 3J coupling constant of 2.1 Hz to that measured for the
known syn-dichloride 29q, which has a 3JHH coupling constant of 2.2 Hz (all
measurements in CDCl3). An authentic sample of the diastereoisomeric dichloride of 29s
was prepared via an anti-selective dichlorination of the (E)-alkene 28s with Cl2 (NMR
experiment), and the vicinal chloride 1H-1H 3J coupling constant was measured as 6.5 Hz
– a similar value to that for anti-configured dichloride 29r (6.3 Hz).
7. The relative configuration within dichloride 29a [δ 4.41–4.39 (m, 2 H, HCCl(1,2))] was
assigned as syn by comparison to an authentic sample of the diastereoisomeric dichloride
[δ 4.29–4.25 (m, 2 H, HCCl(1,2))] prepared via an anti-selective dichlorination of
cycloheptene with Cl2 (NMR experiment).
8. The relative configuration within dichloride 29g [δ 4.07–4.04 (m, 2 H, HCCl(4,5))] was
assigned as syn by comparison to an authentic sample of the diastereoisomeric dichloride
[δ 4.02–3.97 (m, 2 H, HCCl(4,5))] prepared via an anti-selective dichlorination of (E)-4-
octene with Cl2 (NMR experiment).
9. The relative configurations within dichlorides 29b,c were assigned based on symmetry
considerations, as the syn-configured dichlorides would be meso-compounds. The four
sets of 1H and 13C signals within the [1r-(u)-3,4-dichlorocyclopentyl]methoxy moiety
confirmed the syn-assignment. The relative configuration at C(1) in 29c was, however,
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assigned by comparison to an authentic sample of the syn-configured [at C(1)] dichloride,
prepared via a two-step oxidation-deoxochlorination sequence27 from tert-
butyl(cyclopent-3-en-1-ylmethoxy)diphenylsilane (28c), which matched identically. The
relative configuration at C(1) in 29b was in turn assigned via chemical correlation to 29c.
General Procedure IX: anti-Selective Dichlorination of Alkenes with Cl2
An oven-dried, 50-mL, three-necked, round-bottomed flask equipped with a magnetic
stirrer bar was charged with CDCl3 (pre-dried over 3Å molecular sieves, 5.0 mL) via syringe,
then was sealed with a glass stopper and weighed. One of the necks of the flask was connected to
a cylinder containing Cl2 gas, using Tygon® tubing and a Pasteur pipet, while another neck was
vented into a 250-mL Erlenmeyer flask containing 1 M aq. NaOH (50 mL) via Tygon® tubing.
Cl2 gas was gently bubbled into the CDCl3 over 1 min, with stirring, which gave a yellow
solution almost immediately (Note: gentle bubbling was important to minimize evaporation of
CDCl3). The Cl2 gas inlet was then disconnected, all three necks were sealed with a glass
stoppers, and the flask was re-weighed to measure the amount of Cl2 gas that had dissolved in the
CDCl3, thus allowing calculation of the concentration (ca. 0.78 M). (Note: the solution of Cl2 had
a limited lifetime; after ca. 2 h there was a significant loss in concentration, even in the dark). An
oven-dried NMR tube was then charged with the requisite alkene substrate (0.10 mmol, 1.0
equiv), CDCl3 (0.4 mL), and 1,1,2,2-tetrachloroethane (17.4 mg, 11 µL, 0.10 mmol, 1.0 equiv)
via syringe. The solution of Cl2 (130 µL, 0.10 mmol, 1.0 equiv) was then added dropwise via
syringe to the reaction mixture, with shaking at every drop. At the end of the addition, a pale
yellow solution was observed. The resultant mixture was shaken intermittently for 5 min and
then analysed by 1H NMR spectroscopy to obtain spectroscopic data on the corresponding anti-
configured vicinal dichloride. NMR yields were measured against 1,1,2,2-tetrachloroethane as an
internal standard.
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Preparation of tert-Butyl{[(u)-4,5-dichlorohexyl]oxy}diphenylsilane (29i)
Following General Procedure IX, alkene 13 (33.9 mg, 0.10 mmol, 1.0 equiv), CDCl3 (0.4
mL), 1,1,2,2-tetrachloroethane (17.4 mg, 11 µL, 0.10 mmol, 1.0 equiv), and the freshly-prepared
CDCl3 solution of Cl2 (0.78 M, 130 µL, 0.10 mmol, 1.0 equiv) were reacted to give complete
conversion of 13 to anti-dichloride 29i (81% NMR yield). The 1H NMR spectroscopic data
matched that for the catalytic syn-dichlorination of (Z)-alkene 28i.
Preparation of tert-Butyl{[(u)-2,3-dichloro-5-phenylpentyl]oxy}dimethylsilane (S24) and
(u)-2,3-Dichloro-5-phenylpentan-1-ol (29v)
Following General Procedure IX, alkene 28s (27.6 mg, 0.10 mmol, 1.0 equiv), CDCl3
(0.4 mL), 1,1,2,2-tetrachloroethane (17.4 mg, 11 µL, 0.10 mmol, 1.0 equiv), and the freshly-
prepared CDCl3 solution of Cl2 (0.78 M, 130 µL, 0.10 mmol, 1.0 equiv) were reacted to give
complete conversion of 28s to anti-dichloride S24 (59% NMR yield). Partial cleavage of the tert-
butyldimethylsilyl group was also observed in the crude reaction mixture to give 29v (ca. 11%
NMR yield).
Data for S24: 1H NMR: (500 MHz, CDCl3, diagnostic resonances only)
δ 4.22 (ddd, J = 9.8, 6.5, 2.5 Hz, 1 H, HC(3)), 4.12–4.07 (m, 1 H, HC(2))
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Preparation of {[(u)-4,5-Dichloro-7-phenylheptyl]oxy}tri-iso-propylsilane (S25)
Following General Procedure IX, alkene 28j (34.6 mg, 0.10 mmol, 1.0 equiv), CDCl3
(0.4 mL), 1,1,2,2-tetrachloroethane (17.4 mg, 11 µL, 0.10 mmol, 1.0 equiv), and the freshly-
prepared CDCl3 solution of Cl2 (0.80 M, 130 µL, 0.10 mmol, 1.0 equiv) were reacted to give
complete conversion of 28j to anti-dichloride S25 (60% NMR yield) and an unidentified by-
product (19% NMR yield).
Data for S25: 1H NMR: (500 MHz, CDCl3, diagnostic resonances only)
δ 4.08 (ddd, J = 9.4, 6.3, 3.1 Hz, 1 H, HC(4)), 3.96 (ddd, J = 9.1, 6.3, 2.5 Hz, 1 H,
HC(5))
Preparation of (l)-1,2-Dichlorocycloheptane (S26)
Following General Procedure IX (with some modifications to the amounts of reagents),
cycloheptene 28a (19.4 mg, 23.5 µL, 0.20 mmol, 1.0 equiv), CDCl3 (0.4 mL), 1,1,2,2-
tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), and the freshly-prepared CDCl3
solution of Cl2 (0.63 M, 600 µL, 0.38 mmol, 1.9 equiv) were reacted to give complete conversion
of cycloheptene 28a to anti-dichloride S26 (91% NMR yield).
Data for S26: 1H NMR: (500 MHz, CDCl3)
δ 4.29–4.25 (m, 2 H, HC(1,2)), 2.24–2.17 (m, 2 H, HC(3,7)), 2.01–1.93 (m, 2 H,
HC(3,7)), 1.87–1.78 (m, 2 H, HC(4,6)), 1.64–1.53 (m, 4 H, HC(4,5,6))
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Preparation of (u)-4,5-Dichlorooctane (S27)
Following General Procedure IX (with some modifications to the amounts of reagents),
(E)-4-octene 28g (22.5 mg, 31.5 µL, 0.20 mmol, 1.0 equiv), CDCl3 (0.4 mL), 1,1,2,2-
tetrachloroethane (33.3 mg, 21 µL, 0.20 mmol, 1.0 equiv), and the freshly-prepared CDCl3
solution of Cl2 (0.63 M, 600 µL, 0.38 mmol, 1.9 equiv) were reacted to give complete conversion
of (E)-4-octene 28g to anti-dichloride S27 (91% NMR yield).
Data for S27: 1H NMR: (500 MHz, CDCl3)
δ 4.02–3.97 (m, 2 H, HC(4,5)), 1.97–1.89 (m, 2 H, HC(3,6)), 1.82–1.73 (m, 2 H,
HC(3,6)), 1.69–1.60 (m, 2 H, HC(2,7)), 1.48–1.39 (m, 2 H, HC(2,7)), 0.95 (t, J =
7.4 Hz, 6 H, HC(1,8))
Preparation of tert-Butyl{[1r-(u)-3,4-dichlorocyclopentyl]methoxy}diphenylsilane (29c) via
a Two-Step Oxidation-Deoxochlorination Sequence
Preparation of (±)-{[(1R,3s,5S)-6-oxabicyclo[3.1.0]hexan-3-yl]methoxy}(tert-
butyl)diphenylsilane (S28). A flame-dried, 25-mL, round-bottomed flask equipped with a
magnetic stirrer bar was charged with tert-butyl(cyclopent-3-en-1-ylmethoxy)diphenylsilane 28c
(337 mg, 1.00 mmol, 1.0 equiv) then was sealed with a rubber septum and purged with argon via
an inlet needle. CH2Cl2 (5.0 mL) was added via syringe and the mixture was cooled in an ice-
water bath, with stirring, under an argon atmosphere. 3-Chloroperoxybenzoic acid (washed, 207
mg, 1.20 mmol, 1.2 equiv) was then added in one portion against a backflow of argon, and the
resultant mixture was allowed to stir in the ice-water bath for 30 min, followed by a further 1 h at
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rt. The reaction mixture was then transferred to a separatory funnel, diluted with Et2O (20 mL),
and sequentially washed with sat. aq. Na2S2O3 (5 mL), sat. aq. NaHCO3 (10 mL), H2O (10 mL)
and brine (10 mL), then dried (MgSO4), filtered, and concentrated in vacuo (20–23 °C, ca. 20
mm Hg) to give a colourless oil [3.7:1 dr at C(3)]. Purification via flash column chromatography
[24 g SiO2, 24 mm Ø, dry loaded with 1.8 g SiO2, 100:0 → 96:4 hexane/EtOAc (100 mL and
300 mL, respectively), ca. 10 mL fractions] gave S28 as a white solid [313 mg, 89%, 3.7:1 dr at
C(3)].
Data for S28 mp: 68–72 °C
1H NMR: (500 MHz, CD3C1)
δ 7.67–7.62 (m, 4 H, HC(2′,2′′), both diastereoisomers), 7.45–7.35 (m, 6 H,
HC(3′,3′′,4′,4′′), both diastereoisomers), 3.60 (d, J = 5.3 Hz, 2 H, HC(6), major
diastereoisomer), 3.50 (d, J = 8.2 Hz, 2 H, minor diastereoisomer), 3.48 (s, 2 H,
HC(1,5), major diastereoisomer), 3.45 (s, 2 H, HC(1,5), minor diastereoisomer),
2.37–2.28 (m, 1 H, HC(3), minor diastereoisomer), 2.11 (dd, J = 13.5, 7.5 Hz, 2 H,
HC(2,4), major diastereoisomer), 2.14–1.99 (m, 1 H, HC(3), major
diastereoisomer), 1.91 (dd, J = 14.9, 1.5 Hz, 2 H, HC(2,4), minor diastereoisomer),
1.80 (dd, J = 14.9, 9.3 Hz, 2 H, HC(2,4), minor diastereoisomer), 1.53 (dd, J = 13.5,
9.1 Hz, 2 H, HC(2,4), major diastereoisomer), 1.05 (s, 9H, Sit-Bu, both
diastereoisomers). 13C NMR: (126 MHz, CD3C1)
δ 135.5 (C(2′,2′′), both diastereoisomers), 134.1 (C(1′,1′′), minor diastereoisomer),
133.7 (C(1′,1′′), minor diastereoisomer), 129.6 (C(4′,4′′), major diastereoisomer),
129.5 (C(4′,4′′), minor diastereoisomer), 127.6 (C(3′,3′′), major diastereoisomer),
127.5 (C(3′,3′′), minor diastereoisomer), 69.5 (C(6), minor diastereoisomer), 65.7
(C(6), major diastereoisomer), 58.6 (C(1,5), minor diastereoisomer), 57.1 (C(1,5),
major diastereoisomer), 38.1 (C(3), minor diastereoisomer), 35.3 (C(3), major
diastereoisomer), 30.7 (C(2,4), major diastereoisomer), 29.8 (C(2,4), minor
diastereoisomer), 26.9 (SiCMe3, minor diastereoisomer), 26.8 (SiCMe3, major
diastereoisomer), 19.3 (SiCMe3, both diastereoisomers)
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IR: (neat)
3069 (w), 3028 (w), 2951 (m), 2929 (m), 2856 (m), 1588 (w), 1471 (m), 1429 (m),
1376 (m), 1361 (w), 1271 (w), 1201 (w), 1112 (s), 1016 (m), 998 (w), 945 (w),
915 (w), 840 (w), 827 (m), 791 (m), 744 (m), 703 (s), 688 (m), 615 (m)
MS: (ESI+, TOF)
354.2 (18), 353.2 ([M+H]+, 59), 275.2 ([M–Ph]+, 21), 269.2 (10), 233.1 (10), 97.1
([C5H7CH2O]+, 100)
HRMS: (ESI+, TOF)
calcd for C22H29O2Si ([M+H]+): 353.1937, found: 353.1939
TLC: minor diastereoisomer – Rf 0.31 (99:1 hexane/MTBE) [UV/KMnO4]
major diastereoisomer – Rf 0.33 (99:1 hexane/MTBE) [UV/KMnO4]
Preparation of tert-Butyl{[1r-(u)-3,4-dichlorocyclopentyl]methoxy}diphenylsilane
(29c). Following the procedure reported by Yoshimitsu et al.,27 a flame-dried, 25-mL, two-
necked, round-bottomed flask equipped with a magnetic stirrer bar, a glass stopper, and a reflux
condenser (attached at the top to an argon inlet) was charged with S28 (285 mg, 0.81 mmol, 1.0
equiv) and toluene (8.5 mL) via syringe. Triphenylphosphine (637 mg, 2.43 mmol, 3.0 equiv)
and N-chlorosuccinimide (324 mg, 2.43 mmol, 3.0 equiv) were then added sequentially against a
backflow of argon, and the resultant suspension was heated at 90 °C, with stirring (the reaction
quickly darkened to a black-purple mixture). The reaction mixture was allowed to cool to rt and
was quenched with sat. aq. NaHCO3 (1 mL), diluted with H2O (10 mL) and transferred to a
separatory funnel. The mixture was extracted with EtOAc (3 × 10 mL) and the combined organic
extracts were washed with brine (10 mL), then dried (MgSO4), filtered, and concentrated in
vacuo (20–23 °C, ca. 20 mm Hg) to give a yellow gum. Attempted purification via flash column
chromatography failed to separate the dichloride from the remaining triphenylphosphine, and the
resultant mixture (725 mg) was re-dissolved in EtOAc (5 mL). Sat.aq. NaHCO3 (1 mL) and tert-
butyl hydroperoxide (30 wt% in H2O, 0.5 mL) were then added via syringe. The biphasic
mixture was vigorously stirred for ca. 10 min at rt, then was quenched with sat. aq. Na2SO3 (0.5
mL), diluted with H2O (10 mL), transferred to a separatory funnel, and extracted with Et2O (3 ×
10 mL). The combined organic extracts were washed with brine (10 mL), then dried (MgSO4),
filtered, and concentrated in vacuo (20–23 °C, ca. 20 mm Hg) to give a pale yellow oil [3.6:1 dr
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at C(1)]. Purification via flash column chromatography [27 g high porosity grade SiO2, 24 mm
Ø, dry loaded with 1.8 g silica, 100:0 → 99:1 hexane/MTBE (200 mL and 500 mL,
respectively), ca. 10 mL fractions] gave 29c as a colourless, viscous oil [289 mg, 71%, 3.1:1 dr
at C(1)]. The 1H and 13C NMR spectroscopic data for the major syn-diastereoisomer [at C(1)]
matched that for 29c obtained via direct, catalytic syn-dichlorination of tert-butyl(cyclopent-3-
en-1-ylmethoxy)diphenylsilane (28c) (vide supra). The respective 1H chemical shifts and vicinal 1H-1H 3J coupling constants of HC(6) between the syn- and anti- diastereoisomers [at C(1)] of
29c were used to assign a syn-configuration within the related compound [1r-(u)-3,4-
dichlorocyclopentyl]methyl acetate 29b (vide supra).26
Determination of Configurations within Vinylic Chlorides (Figure 2)
Preparation of (E)-tert-Butyl[(4-chlorohex-4-en-1-yl)oxy]diphenylsilane (15) and (E)-tert
Butyl[(5-chlorohex-4-en-1-yl)oxy]diphenylsilane (16) (Figure 2)
An oven-dried, 10-mL Schlenk flask equipped with a magnetic stirrer bar was taken into
the glovebox and charged sequentially with diphenyl diselenide (PhSeSePh) (15.6 mg, 0.05
mmol, 5 mol %), benzyltriethylammonium chloride (BnEt3NCl) (690 mg, 3.03 mmol, 3.0 equiv),
and N-fluoropyridinium tetrafluoroborate 11 (240 mg, 1.30 mmol, 1.3 equiv), and was then
sealed with a rubber septum, removed from the box, and placed under argon. MeCN (3.0 mL)
and chlorotrimethylsilane (Me3SiCl) (218 mg, 255 µL, 2.01 mmol, 2.0 equiv) were then added
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sequentially and stirring was commenced. After ca. 5 min, alkene 13 (339 mg, 1.00 mmol, 1.0
equiv) was added via cannula transfer under argon using two 1.0 mL portions of MeCN, and the
resultant mixture was stirred at rt for 18 h. Sat. aq. NaHCO3 (0.5 mL) was added to quench any
unreacted Me3SiCl, and 30% aq. H2O2 (10 µL, ca. 0.1 mmol) was added subsequently to
decompose any traces of β-chloro phenylselanyl products to the corresponding alkenes. After
stirring for ca. 10 min at rt, sat. aq. Na2SO3 (0.5 mL), H2O (10 mL) and CH2Cl2 (10 mL) were
sequentially added, and the layers were separated. The aqueous layer was extracted with CH2Cl2
(2 × 10 mL) and the combined organic extracts were dried (MgSO4), filtered, and concentrated in
vacuo (45 °C, ca. 5 mm Hg). The resultant residue was eluted through SiO2 to remove any
ammonium salts (10 g SiO2, 20 mm Ø, CH2Cl2, ca. 5 mL fractions) to give a 78:12:10 mixture of
14:15:16 as a yellow oil (408 mg). Purification via flash column chromatography (40 g high
porosity grade SiO2, 30 mm Ø, 99:1 hexane/MTBE, ca. 5 mL fractions), followed by further
purification of the mixed fractions (2 × 20 g high porosity grade SiO2, 20 mm Ø, 99:1
hexane/MTBE, ca. 2.5 mL fractions), gave, in order of elution, a 59:41 mixture of 15:16 as a
pale yellow oil (52.6 mg, 14%) and 14 as a colorless oil (260 mg). Further purification of 14 via
Kugelrohr distillation at reduced pressure [160 °C (ABT), 10–5 mm Hg] gave 14 as a clear,
colorless oil (257 mg, 63%, >99:1 dr, contaminated with 4% of an unidentified terminal alkene
impurity). The mixture of 15 and 16 was dissolved in CDCl3 and subjected to 1D NOESY
experiments, which established their configurations as (E) (see reciprocal enhancements
highlighted in blue, above).
Data for mixture of 15 and 16: 1H NMR: (500 MHz, CDCl3)
δ 7.69–7.64 (m, 4 H each, HC(2ʹ,2ʹʹ), 15 & 16), 7.46–7.36 (m, 6 H each,
HC(3ʹ,3ʹʹ,4ʹ,4ʹʹ), 15 & 16), 5.65 (q, J = 7.1 Hz, 1 H, HC(5), 15), 5.56 (t, J = 7.9 Hz,
1 H, HC(4), 16), 3.71–3.64 (m, 2 H each, HC(1), 15 & 16), 2.49 (t, J = 7.4 Hz, 2 H,
HC(3), 15), 2.15 (app q, J = 7.5 Hz, 2 H, HC(3), 16), 2.04 (s, 3 H, HC(16)), 1.82–
1.76 (m, 2 H, HC(2), 15), 1.65 (d, J = 7.1 Hz, 3 H, HC(6), 15), 1.64–1.58 (m, 2 H,
HC(2), 16), 1.06 (s, 9 H each, Sit-Bu, 15 & 16) 13C NMR: (125 MHz, CDCl3)
δ 135.5 (C(2ʹ,2ʹʹ), 15 & 16), 133.9, 133.8, 133.8 (C(1ʹ,1ʹʹ) for 15 & 16, C(4) for 15,
C(5) for 16), 129.5, 129.5 (C(4ʹ,4ʹʹ), 15 & 16), 127.6, 127.6 (C(3ʹ,3ʹʹ), 15 & 16),
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127.3 (C(4), 16), 122.5 (C(5), 15), 62.8, 62.5 (C(1), 15 & 16), 32.0 (C(2), 16), 30.1
(C(2), 15), 29.7 (C(3), 15), 26.8 (SiCMe3, 15 & 16), 25.0 (C(3), 16), 20.7 (C(6), 16),
19.2 (SiCMe3, 15 & 16), 13.8 (C(6), 15)
MS: (EI+, DFSF)
373.2 ([M+H]+, 4), 337.2 (20), 317.1 (29), 316.1 (19), 315.1 (78), 297.1 (17), 296.1
(10), 295.1 (46), 287.1 (11), 281.1 (15), 269.1 (38), 267.1 (16), 261.1 (12), 254.1
(16), 253.1 (72), 240.1 (12), 239.1 (53), 233.1 (44), 217.0 (24), 199.0 (13), 197.0
(13), 191.1 (21), 181.1 (14), 179.1 (11), 157.1 (11), 135.0 (10), 117.0 (27), 99.1
(23), 92.1 (21), 91.1 (100), 81.1 (52), 75.0 (12)
HRMS: (ESI+, TOF)
calcd for C22H30ClOSi ([M+H]+): 373.1754, found: 373.1768
Preparation of (Z)-tert-Butyl[(4-chlorohex-4-en-1-yl)oxy]diphenylsilane (S29) and (Z)-tert-
Butyl[(5-chlorohex-4-en-1-yl)oxy]diphenylsilane (S30)
An oven-dried, 10-mL Schlenk flask equipped with a magnetic stirrer bar was taken into
the glovebox and charged sequentially with diphenyl diselenide (PhSeSePh) (15.6 mg, 0.05
mmol, 5 mol %), benzyltriethylammonium chloride (BnEt3NCl) (690 mg, 3.03 mmol, 3.0 equiv),
and N-fluoropyridinium tetrafluoroborate 11 (240 mg, 1.30 mmol, 1.3 equiv), and was then
sealed with a rubber septum, removed from the box, and placed under argon. MeCN (3.0 mL)
and chlorotrimethylsilane (Me3SiCl) (218 mg, 255 µL, 2.01 mmol, 2.0 equiv) were then added
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sequentially and stirring was commenced. After ca. 5 min, alkene 28i (339 mg, 1.00 mmol, 1.0
equiv) was added via cannula transfer under argon using two 1.0 mL portions of MeCN, and the
resultant mixture was stirred at rt for 18 h. Sat. aq. NaHCO3 (0.5 mL) was added to quench any
unreacted Me3SiCl, and 30% aq. H2O2 (10 µL, ca. 0.1 mmol) was added subsequently to
decompose any traces of β-chloro phenylselanyl products to the corresponding alkenes. After
stirring for ca. 10 min at rt, sat. aq. Na2SO3 (0.5 mL), H2O (10 mL) and CH2Cl2 (10 mL) were
sequentially added, and the layers were separated. The aqueous layer was extracted with CH2Cl2
(2 × 10 mL) and the combined organic extracts were dried (MgSO4), filtered, and concentrated in
vacuo (45 °C, ca. 5 mm Hg). The resultant residue was eluted through SiO2 to remove any
ammonium salts (10 g SiO2, 20 mm Ø, CH2Cl2, ca. 5 mL fractions) to give a 77:12:11 mixture of
29i:S29:S30 as a yellow oil (397 mg). Purification via flash column chromatography (40 g high
porosity grade SiO2, 30 mm Ø, 99:1 hexane/MTBE, ca. 5 mL fractions), followed by further
purification of the mixed fractions (40 g high porosity grade SiO2, 30 mm Ø, 99:1 hexane/MTBE,
ca. 5 mL fractions), gave, in order of elution, a 57:43 mixture of S29:S30 as a pale yellow oil
(61.2 mg, 16%) and 29i as a colorless oil (263 mg). Further purification of 29i via Kugelrohr
distillation at reduced pressure [160 °C (ABT), 10–5 mm Hg] gave 29i as a clear, colorless oil
(258 mg, 63%, >99:1 dr). The mixture of S29 and S32 was dissolved in CDCl3 and subjected to
1D NOESY experiments, which established their configurations as (Z) (see reciprocal
enhancements highlighted in blue, above).
Data for mixture of S29 and S30: 1H NMR: (500 MHz, CDCl3)
δ 7.69–7.65 (m, 4 H each, HC(2ʹ,2′′), S29 & S30), 7.45–7.36 (m, 6 H each,
HC(3ʹ,3′′,4′,4′′), S29 & S30), 5.50 (q, J = 6.6 Hz, 1 H, HC(5), S29), 5.41 (tq, J = 7.0,
1.3 Hz, 1 H, HC(4), S30), 3.69–3.65 (m, 2 H each, HC(1), S29 & S30), 2.44 (t, J =
7.3 Hz, 2 H, HC(3), S29), 2.28–2.22 (m, 2 H, HC(3), S30), 2.06 (app q, J = 1.3 Hz,
3 H, HC(6), S30), 1.83–1.77 (m, 2 H, HC(2), S29), 1.69 (dt, J = 6.5, 1.2 Hz, 3 H,
HC(6), S29), 1.67–1.61 (m, 2 H, HC(2), S30), 1.06 (s, 9 H each, Sit-Bu, S29 &
S30) 13C NMR: (125 MHz, CDCl3)
δ 135.7, 135.7 (C(2ʹ,2′′), S29 & S30), 135.3, 134.2, 134.1 (C(1ʹ,1′′) for S29 & S30,
C(4) for S29, C(5) for S30), 129.7, 129.7 (C(4ʹ,4′′), S29 & S30), 127.8, 127.7
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(C(3ʹ,3′′), S29 & S30), 125.6 (C(4), S30), 120.2 (C(5), S29), 63.5, 62.7 (C(1), S29
& S30), 36.0 (C(3), S29), 31.7 (C(2), S30), 30.5 (C(2), S29), 27.0 (SiCMe3, S29 &
S30), 26.3 (C(6), S30), 25.4 (C(3), S30), 19.4, 19.4 (SiCMe3, S29 & S30), 14.1
(C(6), S29)
MS: (CI+, DFSF)
373.1 ([M+H]+, 7), 337.2 (29), 317.1 (36), 316.1 (23), 315.1 (100), 297.1 (21),
296.1 (13), 295.1 (59), 287.0 (22), 281.1 (15), 269.1 (23), 267.1 (25), 261.1 (12),
240.1 (11), 239.1 (50), 219.0 (12), 217.0 (34), 199.0 (11), 197.0 (15), 157.1 (15),
117.0 (30), 99.1 (13), 81.1 (79)
HRMS: (ESI+, TOF)
calcd for C22H30C2OSi ([M+H]+): 373.1754, found: 373.1757
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Table of Problematic Substrates
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0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
2.97
2.10
2.07
1.06
2.00
2.00
2.04
2.07
2.08
2.10
2.11
2.44
2.44
2.45
2.46
2.47
2.48
2.48
2.50
2.50
2.50
2.55
2.56
2.57
2.58
2.58
2.59
2.60
2.61
2.63
2.63
2.64
3.96
3.98
5.64
7.26
Cresswell, Eey and Denmark S128NATURE CHEMISTRY | www.nature.com/naturechemistry 128© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
20.9
35.7
35.9
68.1
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
129.
3
171.
2
Cresswell, Eey and Denmark S129NATURE CHEMISTRY | www.nature.com/naturechemistry 129© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
9.28
2.00
2.00
0.99
2.00
1.83
5.97
3.96
1.07
2.14
2.15
2.18
2.42
2.44
2.45
2.47
2.52
2.53
2.55
2.56
2.58
2.59
3.58
3.59
3.60
3.60
5.66
5.66
7.26
7.38
7.39
7.41
7.42
7.44
7.45
7.68
7.68
7.69
7.69
7.70
7.70
Cresswell, Eey and Denmark S130NATURE CHEMISTRY | www.nature.com/naturechemistry 130© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
19.3
26.9
35.5
39.4
67.7
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
127.
612
9.5
129.
613
4.1
135.
6
Cresswell, Eey and Denmark S131NATURE CHEMISTRY | www.nature.com/naturechemistry 131© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
8.94
2.00
2.00
2.00
0.99
6.17
4.05
1.09
2.33
2.34
2.34
2.35
2.35
2.35
2.36
2.36
2.37
2.37
2.38
2.38
3.74
3.75
3.76
5.04
5.04
5.06
5.06
5.06
5.07
5.08
5.10
5.11
5.11
5.11
5.83
5.84
5.85
5.86
5.86
5.88
5.89
5.89
5.90
5.91
7.26
7.39
7.40
7.40
7.41
7.41
7.43
7.43
7.44
7.44
7.45
7.45
7.46
7.46
7.47
7.47
7.70
7.71
7.71
7.72
7.72
7.72
7.73
Cresswell, Eey and Denmark S132NATURE CHEMISTRY | www.nature.com/naturechemistry 132© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
19.2
26.8
37.2
63.5
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
116.
3
127.
612
9.5
133.
913
5.4
135.
6
Cresswell, Eey and Denmark S133NATURE CHEMISTRY | www.nature.com/naturechemistry 133© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
2.95
1.99
1.94
1.95
1.97
0.97
0.99
1.00
4.03
1.61
1.62
1.63
1.63
1.67
1.68
1.70
1.71
1.72
2.13
2.13
2.13
2.15
2.16
2.16
2.16
2.17
2.18
2.18
3.48
3.49
3.51
4.52
5.36
5.37
5.37
5.38
5.39
5.39
5.39
5.40
5.40
5.41
5.41
5.42
5.42
5.42
5.45
5.45
5.45
5.46
5.46
5.47
5.47
5.48
5.48
5.49
5.50
5.50
5.51
5.51
7.27
7.28
7.28
7.29
7.30
7.31
7.31
7.32
7.33
7.34
7.35
7.36
Cresswell, Eey and Denmark S134NATURE CHEMISTRY | www.nature.com/naturechemistry 134© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
12.7
23.4
29.5
69.8
72.9
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
124.
312
7.4
127.
612
8.3
129.
9
138.
6
Cresswell, Eey and Denmark S135NATURE CHEMISTRY | www.nature.com/naturechemistry 135© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
9.01
5.00
1.99
2.00
2.00
6.08
4.03
1.06
1.60
1.62
1.63
1.64
1.66
2.07
2.08
2.09
2.11
3.66
3.67
3.69
5.37
5.38
5.40
5.41
5.41
5.42
5.42
5.43
5.45
5.46
7.26
7.37
7.38
7.39
7.40
7.42
7.42
7.43
7.44
7.45
7.45
7.68
7.68
7.69
7.70
Cresswell, Eey and Denmark S136NATURE CHEMISTRY | www.nature.com/naturechemistry 136© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
17.9
19.2
26.8
28.8
32.4
63.3
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
125.
012
7.6
129.
513
0.9
134.
113
5.6
Cresswell, Eey and Denmark S137NATURE CHEMISTRY | www.nature.com/naturechemistry 137© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
9.03
5.00
1.98
2.02
2.00
6.13
4.08
1.09
1.62
1.63
1.64
1.64
1.64
1.65
1.66
1.68
2.15
2.16
2.18
2.19
3.69
3.71
3.72
5.37
5.37
5.38
5.38
5.39
5.39
5.40
5.40
5.41
5.42
5.44
5.46
5.48
5.48
5.49
5.49
5.50
5.51
7.26
7.39
7.39
7.40
7.41
7.42
7.43
7.44
7.44
7.45
7.45
7.46
7.46
7.46
7.70
7.70
7.71
7.72
7.72
Cresswell, Eey and Denmark S138NATURE CHEMISTRY | www.nature.com/naturechemistry 138© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
12.7
19.2
23.2
26.9
32.5
63.4
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
124.
112
7.6
129.
513
0.1
134.
113
5.6
Cresswell, Eey and Denmark S139NATURE CHEMISTRY | www.nature.com/naturechemistry 139© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
22.5
0
2.01
1.99
1.97
2.00
2.00
1.98
3.02
2.39
1.04
1.05
1.06
1.07
1.07
1.08
1.09
1.10
1.11
1.56
1.58
1.59
1.61
1.62
2.04
2.06
2.07
2.08
2.28
2.30
2.31
2.31
2.33
2.65
2.67
2.68
3.65
3.67
3.68
5.42
5.44
5.46
5.46
5.47
5.47
5.47
5.48
5.50
5.51
7.17
7.18
7.18
7.19
7.26
7.26
7.28
7.29
Cresswell, Eey and Denmark S140NATURE CHEMISTRY | www.nature.com/naturechemistry 140© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
12.0
18.0
28.8
32.8
34.5
36.1
62.8
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
125.
712
8.2
128.
412
9.6
130.
6
142.
2
Cresswell, Eey and Denmark S141NATURE CHEMISTRY | www.nature.com/naturechemistry 141© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
2.00
1.98
1.17
5.09
2.00
2.00
1.97
0.82
0.83
0.83
0.84
0.85
0.85
0.96
0.97
0.98
0.98
0.98
0.99
1.56
1.57
1.58
1.59
1.60
1.61
1.61
1.63
1.65
1.66
1.68
1.69
1.71
2.02
2.04
2.05
2.07
4.04
4.06
4.07
5.37
5.38
5.40
5.41
5.42
5.43
5.44
5.45
5.46
5.47
5.49
7.26
Cresswell, Eey and Denmark S142NATURE CHEMISTRY | www.nature.com/naturechemistry 142© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
8.3
12.9
17.9
28.5
28.8
64.0
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
125.
7
130.
0
174.
9
Cresswell, Eey and Denmark S143NATURE CHEMISTRY | www.nature.com/naturechemistry 143© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.06
2.00
2.03
1.99
2.00
2.04
1.15
2.03
1.60
1.60
1.61
1.61
2.21
2.22
2.23
2.24
2.25
2.25
2.49
2.50
2.52
3.68
5.32
5.32
5.33
5.33
5.35
5.35
5.36
5.36
5.37
5.38
5.39
5.39
5.40
5.41
5.42
5.43
5.44
5.45
5.45
7.19
7.19
7.21
7.21
7.25
7.25
7.26
7.26
7.28
7.28
7.28
7.32
7.33
7.34
7.35
Cresswell, Eey and Denmark S144NATURE CHEMISTRY | www.nature.com/naturechemistry 144© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200210f1 (ppm)
17.8
26.7
41.7
50.2
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
125.
912
6.9
128.
712
9.4
129.
413
4.2
207.
8
Cresswell, Eey and Denmark S145NATURE CHEMISTRY | www.nature.com/naturechemistry 145© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.04
2.04
1.97
1.98
2.00
2.00
1.97
0.96
4.32
1.62
1.62
1.63
1.63
1.65
1.66
1.67
1.67
1.68
2.08
2.09
2.10
2.10
2.11
2.11
2.12
2.12
2.89
3.66
3.68
3.69
3.69
3.70
3.70
3.71
3.73
3.84
3.86
3.86
3.87
3.87
3.87
3.88
3.90
5.36
5.37
5.39
5.40
5.41
5.41
5.42
5.43
5.44
5.45
5.46
7.20
7.21
7.21
7.22
7.22
7.22
7.23
7.23
7.24
7.25
7.26
7.26
7.27
7.27
7.28
7.28
7.29
7.29
7.29
Cresswell, Eey and Denmark S146NATURE CHEMISTRY | www.nature.com/naturechemistry 146© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200210f1 (ppm)
17.9
26.6
37.8
43.9
65.3
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
111.
1
124.
812
6.3
127.
913
0.5
130.
8
136.
8
Cresswell, Eey and Denmark S147NATURE CHEMISTRY | www.nature.com/naturechemistry 147© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.07
2.00
2.08
3.00
2.04
0.99
1.01
1.63
1.63
1.64
1.64
1.64
1.65
2.11
2.12
2.14
2.15
2.23
2.24
2.26
2.27
3.72
5.36
5.36
5.37
5.38
5.38
5.39
5.39
5.40
5.41
5.41
5.42
5.42
5.43
5.44
5.45
5.46
5.47
5.48
5.49
5.50
5.50
5.80
5.80
5.81
5.83
5.84
5.84
6.93
6.94
6.95
6.96
6.97
6.99
7.26
Cresswell, Eey and Denmark S148NATURE CHEMISTRY | www.nature.com/naturechemistry 148© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
17.9
30.9
32.2
51.4
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
121.
0
126.
112
9.5
149.
0
167.
1
Cresswell, Eey and Denmark S149NATURE CHEMISTRY | www.nature.com/naturechemistry 149© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
9.06
5.07
1.98
2.05
2.00
1.92
2.66
1.81
1.45
1.52
1.54
1.55
1.57
1.58
1.93
1.94
1.94
1.95
1.95
1.98
1.99
2.01
2.02
3.18
3.19
3.20
4.42
5.34
5.34
5.36
5.36
5.37
5.37
5.38
5.38
5.39
5.39
5.42
5.42
5.43
5.44
5.45
5.45
5.47
5.48
5.48
5.48
7.25
7.26
7.27
7.32
7.34
7.35
Cresswell, Eey and Denmark S150NATURE CHEMISTRY | www.nature.com/naturechemistry 150© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
0.8
CD3C
N1.
0 CD
3CN
1.2
CD3C
N1.
3 CD
3CN
1.5
CD3C
N1.
7 CD
3CN
1.8
CD3C
N
13.1
25.1
29.0
29.1
47.7
51.4
80.1
118.
0
125.
212
8.1
128.
512
9.5
131.
0
140.
4
156.
7
Cresswell, Eey and Denmark S151NATURE CHEMISTRY | www.nature.com/naturechemistry 151© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
2.96
2.02
1.92
1.99
0.99
1.01
2.00
1.99
1.55
1.56
1.57
1.57
1.69
1.70
1.72
1.73
1.75
2.06
2.07
2.09
2.10
3.65
3.66
3.67
5.32
5.33
5.33
5.33
5.34
5.34
5.35
5.35
5.35
5.36
5.36
5.37
5.38
5.38
5.40
5.41
5.41
5.42
5.42
5.42
5.43
5.43
5.43
5.44
5.44
5.45
5.45
5.46
5.46
5.47
5.47
7.26
7.66
7.66
7.67
7.68
7.68
7.69
7.69
7.70
7.79
7.79
7.80
7.80
7.81
7.81
7.82
7.82
Cresswell, Eey and Denmark S152NATURE CHEMISTRY | www.nature.com/naturechemistry 152© 2015 Macmillan Publishers Limited. All rights reserved
-100102030405060708090100110120130140150160170180190200210220f1 (ppm)
12.7
24.2
28.2
37.6
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
123.
012
4.8
129.
013
2.1
133.
7
168.
3
Cresswell, Eey and Denmark S153NATURE CHEMISTRY | www.nature.com/naturechemistry 153© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
2.94
9.07
1.98
2.00
1.94
1.00
0.98
6.09
4.01
0.90
0.92
0.93
1.08
1.37
1.38
1.40
1.41
1.43
1.44
2.00
2.00
2.01
2.03
2.04
2.04
4.17
4.18
4.18
4.18
4.19
5.54
5.54
5.54
5.56
5.57
5.57
5.58
5.58
5.58
5.59
5.59
5.64
5.64
5.65
5.65
5.66
5.66
5.67
5.67
5.68
5.68
5.69
5.70
5.70
7.26
7.37
7.38
7.38
7.39
7.39
7.40
7.42
7.42
7.42
7.43
7.43
7.44
7.45
7.45
7.70
7.70
7.71
7.72
7.72
Cresswell, Eey and Denmark S154NATURE CHEMISTRY | www.nature.com/naturechemistry 154© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
13.7
19.2
22.4
26.9
34.3
64.7
76.7
77.0
77.3
127.
512
7.6
128.
812
9.5
131.
213
3.9
135.
6
Cresswell, Eey and Denmark S155NATURE CHEMISTRY | www.nature.com/naturechemistry 155© 2015 Macmillan Publishers Limited. All rights reserved
-2.0-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
6.00
9.04
1.97
2.00
1.98
0.99
1.00
3.01
2.04
0.08
0.08
0.08
0.08
0.09
0.09
0.92
0.92
0.93
0.93
0.93
0.93
2.35
2.36
2.36
2.37
2.37
2.37
2.37
2.38
2.38
2.38
2.39
2.40
2.40
2.40
2.70
2.71
2.72
2.73
4.13
4.13
4.14
4.14
4.14
4.14
4.15
4.15
5.58
5.58
5.60
5.61
5.61
5.62
5.62
5.69
5.70
5.71
5.73
5.73
7.18
7.18
7.19
7.19
7.19
7.20
7.20
7.21
7.21
7.21
7.26
7.28
7.29
7.29
7.29
7.30
7.30
7.31
7.31
Cresswell, Eey and Denmark S156NATURE CHEMISTRY | www.nature.com/naturechemistry 156© 2015 Macmillan Publishers Limited. All rights reserved
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-5.1
18.4
26.0
34.0
35.6
63.9
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
125.
712
8.2
128.
412
9.8
130.
2
141.
9
Cresswell, Eey and Denmark S157NATURE CHEMISTRY | www.nature.com/naturechemistry 157© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
1.05
2.04
1.97
2.00
1.91
4.96
1.74
4.03
4.04
4.04
4.05
4.05
4.14
4.15
4.15
4.16
4.53
4.65
5.82
5.83
5.84
5.85
5.86
5.87
5.89
5.90
5.91
5.92
5.93
5.94
7.27
7.28
7.28
7.29
7.30
7.31
7.31
7.34
7.35
Cresswell, Eey and Denmark S158NATURE CHEMISTRY | www.nature.com/naturechemistry 158© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
62.9
70.0
72.3
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
127.
612
7.712
8.4
132.
2
138.
1
Cresswell, Eey and Denmark S159NATURE CHEMISTRY | www.nature.com/naturechemistry 159© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
6.00
4.03
4.06
3.81
6.80
6.82
7.26
7.50
7.51
Cresswell, Eey and Denmark S160NATURE CHEMISTRY | www.nature.com/naturechemistry 160© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
55.3
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
114.
7
122.
0
135.
413
5.4
135.
4
160.
1
Cresswell, Eey and Denmark S161NATURE CHEMISTRY | www.nature.com/naturechemistry 161© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
6.00
2.00
2.07
1.99
2.00
3.91
6.81
6.81
6.83
6.83
6.86
6.86
6.87
6.88
6.89
6.89
7.20
7.20
7.21
7.21
7.21
7.21
7.23
7.23
7.26
7.55
7.55
7.56
7.57
Cresswell, Eey and Denmark S162NATURE CHEMISTRY | www.nature.com/naturechemistry 162© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
55.9
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
110.
1
118.
612
1.9
128.
113
0.6
156.
8
Cresswell, Eey and Denmark S163NATURE CHEMISTRY | www.nature.com/naturechemistry 163© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
2.06
4.05
2.00
2.00
1.39
1.40
1.41
1.42
1.43
1.43
1.44
1.45
1.45
1.46
1.76
1.77
1.78
1.78
1.79
1.81
1.81
1.82
1.83
1.84
1.86
1.87
1.88
2.09
2.09
2.10
2.10
2.11
2.13
2.13
2.14
2.15
4.27
4.28
4.28
4.29
7.26
Cresswell, Eey and Denmark S164NATURE CHEMISTRY | www.nature.com/naturechemistry 164© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
22.1
32.3
62.7
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
Cresswell, Eey and Denmark S165NATURE CHEMISTRY | www.nature.com/naturechemistry 165© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.09
3.05
2.00
2.00
1.98
1.46
1.47
1.47
1.48
1.48
1.49
1.49
1.50
1.50
1.51
1.52
1.53
1.54
1.55
1.55
1.56
1.56
1.56
1.57
1.58
1.58
1.58
1.59
1.59
1.60
1.61
1.61
1.62
1.68
1.69
1.69
1.70
1.71
1.71
1.72
1.72
1.73
1.73
1.73
1.73
1.74
1.74
1.75
1.76
1.76
1.77
1.77
1.78
1.79
1.79
1.80
1.81
1.94
1.94
1.95
1.95
1.96
1.97
1.97
1.98
1.98
1.98
1.99
2.00
2.00
2.01
2.15
2.16
2.17
2.18
2.18
2.18
2.19
2.20
2.21
2.21
2.21
2.22
4.39
4.39
4.39
4.39
4.40
4.41
4.41
4.41
7.26
Cresswell, Eey and Denmark S166NATURE CHEMISTRY | www.nature.com/naturechemistry 166© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
23.4
25.6
34.1
66.2
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
Cresswell, Eey and Denmark S167NATURE CHEMISTRY | www.nature.com/naturechemistry 167© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
0.18
1.87
3.35
0.17
2.11
1.21
0.17
0.23
2.00
2.00
0.28
1.91
1.91
1.92
1.92
1.92
1.93
1.93
1.94
1.95
1.95
1.96
1.96
1.97
1.97
1.99
2.00
2.00
2.00
2.00
2.02
2.03
2.05
2.06
2.26
2.27
2.28
2.29
2.30
2.31
2.32
2.33
2.33
2.34
2.35
2.36
2.37
2.38
2.39
2.41
2.41
2.42
2.43
2.43
2.44
2.44
2.45
2.46
2.47
2.77
2.78
2.79
2.79
2.80
2.81
2.81
2.82
2.83
2.83
2.84
2.85
3.99
4.00
4.11
4.12
4.28
4.28
4.28
4.28
4.29
4.29
4.30
4.30
4.31
4.31
4.33
4.33
4.34
4.35
4.36
4.36
7.26
Cresswell, Eey and Denmark S168NATURE CHEMISTRY | www.nature.com/naturechemistry 168© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
20.9
33.7
34.2
36.0
36.1
62.0
62.6
66.9
68.1
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
170.
9
Cresswell, Eey and Denmark S169NATURE CHEMISTRY | www.nature.com/naturechemistry 169© 2015 Macmillan Publishers Limited. All rights reserved
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
10.2
2
2.24
3.33
0.11
0.19
1.97
2.01
0.20
6.93
4.60
1.06
1.99
2.00
2.01
2.03
2.04
2.06
2.08
2.09
2.10
2.20
2.21
2.22
2.23
2.24
2.26
2.27
2.28
2.30
2.31
2.33
2.34
2.36
2.37
2.62
2.64
2.65
2.66
2.66
2.68
2.68
2.69
2.71
3.56
3.57
3.69
3.70
4.27
4.28
4.28
4.29
4.30
4.36
4.37
4.38
4.38
4.39
7.26
7.37
7.38
7.38
7.39
7.39
7.41
7.42
7.42
7.43
7.43
7.44
7.44
7.45
7.45
7.45
7.63
7.63
7.63
7.64
7.64
7.65
7.65
7.65
7.66
7.66
7.67
7.67
Cresswell, Eey and Denmark S170NATURE CHEMISTRY | www.nature.com/naturechemistry 170© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
19.3
26.8
26.9
35.7
35.9
36.8
37.7
62.3
63.4
66.2
67.9
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
127.7
127.7
129.
612
9.8
133.
313
3.6
135.
5
Cresswell, Eey and Denmark S171NATURE CHEMISTRY | www.nature.com/naturechemistry 171© 2015 Macmillan Publishers Limited. All rights reserved
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
8.90
1.01
1.02
1.02
1.98
1.00
0.99
6.03
4.01
1.08
1.83
1.84
1.85
1.85
1.86
1.87
1.88
1.88
1.89
1.90
2.26
2.26
2.27
2.27
2.28
2.29
2.29
2.30
2.30
2.31
2.31
2.32
3.74
3.75
3.76
3.78
3.81
3.82
3.82
3.83
3.83
3.84
3.84
3.85
3.86
3.88
3.89
3.90
3.90
3.91
3.91
3.92
3.93
4.40
4.40
4.41
4.41
4.41
4.42
4.42
4.42
4.43
4.43
4.44
4.44
4.45
7.26
7.39
7.40
7.40
7.40
7.41
7.41
7.42
7.43
7.43
7.44
7.44
7.44
7.44
7.46
7.46
7.46
7.47
7.47
7.67
7.68
7.68
7.68
7.69
7.69
7.70
7.70
7.70
7.71
7.71
Cresswell, Eey and Denmark S172NATURE CHEMISTRY | www.nature.com/naturechemistry 172© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
19.2
26.8
37.9
48.7
58.0
60.1
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
127.7
129.
713
3.3
133.
413
5.5
135.
5
Cresswell, Eey and Denmark S173NATURE CHEMISTRY | www.nature.com/naturechemistry 173© 2015 Macmillan Publishers Limited. All rights reserved
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
5.91
5.92
2.97
3.00
1.00
0.97
1.93
1.93
1.93
5.91
1.35
1.41
1.63
1.64
1.66
1.67
1.68
1.69
1.70
1.71
1.71
1.73
1.74
1.76
1.79
1.80
1.81
1.82
1.83
1.84
1.85
1.86
1.86
1.87
1.88
1.89
1.90
1.91
1.92
2.04
2.05
2.06
2.07
2.08
2.09
2.10
2.10
2.11
2.15
2.15
2.18
2.18
2.19
2.19
2.20
2.20
2.20
2.21
2.22
2.22
2.23
3.53
3.55
3.56
3.58
3.63
3.64
3.65
3.66
3.66
3.67
3.68
3.76
3.77
3.77
3.78
3.78
3.79
3.79
3.80
4.04
4.05
4.05
4.06
4.07
4.07
4.08
4.09
4.10
4.10
4.11
4.12
4.13
4.14
4.16
7.26
Cresswell, Eey and Denmark S174NATURE CHEMISTRY | www.nature.com/naturechemistry 174© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
25.6
25.6
26.9
29.8
30.2
31.1
31.7
48.0
48.1
60.7
61.0
69.2
69.3
75.0
75.6
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
109.
010
9.1
Cresswell, Eey and Denmark S175NATURE CHEMISTRY | www.nature.com/naturechemistry 175© 2015 Macmillan Publishers Limited. All rights reserved
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
1.03
1.02
1.02
0.99
1.02
2.00
1.06
2.07
2.97
2.98
3.00
3.01
3.19
3.20
3.22
3.23
3.63
3.64
3.65
3.67
3.71
3.72
3.73
3.74
4.18
4.19
4.19
4.20
4.21
4.22
4.23
5.96
6.71
6.71
6.72
6.73
6.76
6.77
6.78
Cresswell, Eey and Denmark S176NATURE CHEMISTRY | www.nature.com/naturechemistry 176© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
40.6
47.3
61.0
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
101.
0
108.
310
9.8
122.
7
129.
8
146.
714
7.7
Cresswell, Eey and Denmark S177NATURE CHEMISTRY | www.nature.com/naturechemistry 177© 2015 Macmillan Publishers Limited. All rights reserved
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
2.98
1.09
1.04
1.01
1.00
0.93
0.94
0.95
0.97
1.37
1.38
1.39
1.41
1.41
1.42
1.43
1.44
1.45
1.47
1.55
1.56
1.57
1.58
1.58
1.59
1.60
1.61
1.63
1.63
1.64
1.66
1.75
1.76
1.77
1.78
1.79
1.80
1.81
1.82
1.83
1.85
1.85
1.86
1.87
1.87
1.88
1.89
1.89
1.90
1.91
1.91
4.04
4.04
4.05
4.05
4.06
4.06
4.07
4.07
7.26
Cresswell, Eey and Denmark S178NATURE CHEMISTRY | www.nature.com/naturechemistry 178© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
13.5
19.9
36.4
65.3
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
Cresswell, Eey and Denmark S179NATURE CHEMISTRY | www.nature.com/naturechemistry 179© 2015 Macmillan Publishers Limited. All rights reserved
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.08
1.02
2.04
1.01
2.06
1.01
1.00
2.05
5.14
1.57
1.58
1.69
1.71
1.72
1.74
1.75
1.76
1.80
1.81
1.82
1.83
1.84
1.85
1.86
1.89
1.91
1.92
1.93
2.06
2.06
2.07
2.08
2.08
2.10
2.10
2.11
2.12
3.50
3.51
3.52
3.52
3.53
3.54
3.54
3.55
4.02
4.03
4.03
4.04
4.05
4.05
4.23
4.24
4.25
4.25
4.26
4.27
4.27
4.28
4.49
4.51
4.51
4.54
7.26
7.28
7.28
7.29
7.29
7.30
7.31
7.31
7.33
7.34
7.36
7.36
7.37
Cresswell, Eey and Denmark S180NATURE CHEMISTRY | www.nature.com/naturechemistry 180© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
20.8
26.9
30.9
60.0
66.1
69.4
72.9
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
127.
612
7.6
128.
4
138.
3
Cresswell, Eey and Denmark S181NATURE CHEMISTRY | www.nature.com/naturechemistry 181© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
2.93
2.18
1.04
1.00
2.04
0.96
0.99
2.02
5.08
1.61
1.63
1.70
1.71
1.72
1.73
1.74
1.76
1.77
1.78
1.78
1.80
1.80
1.81
1.82
1.83
1.84
1.85
1.90
1.91
1.92
1.93
1.93
1.94
1.95
1.95
1.96
1.96
1.97
1.98
2.12
2.12
2.13
2.14
2.14
2.15
2.15
2.16
2.17
2.18
2.18
3.48
3.49
3.50
3.51
3.52
3.53
3.53
3.54
3.55
3.56
3.96
3.96
3.97
3.98
3.98
3.99
4.00
4.09
4.10
4.11
4.13
4.14
4.49
4.51
4.52
4.54
7.26
7.27
7.28
7.28
7.29
7.30
7.30
7.31
7.33
7.34
7.36
7.36
7.37
7.37
Cresswell, Eey and Denmark S182NATURE CHEMISTRY | www.nature.com/naturechemistry 182© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
21.9
26.5
31.9
60.2
67.1
69.3
72.9
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
127.
612
7.6
128.
4
138.
4
Cresswell, Eey and Denmark S183NATURE CHEMISTRY | www.nature.com/naturechemistry 183© 2015 Macmillan Publishers Limited. All rights reserved
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
8.96
2.81
0.96
1.91
0.93
1.94
0.91
0.91
6.00
3.98
1.07
1.57
1.58
1.64
1.65
1.66
1.66
1.68
1.69
1.69
1.71
1.79
1.80
1.81
1.82
1.82
1.83
1.84
1.86
1.87
2.08
2.09
2.10
2.10
2.11
2.12
2.14
3.68
3.70
3.70
3.71
3.72
3.72
3.73
3.74
3.74
4.03
4.03
4.04
4.05
4.05
4.06
4.21
4.22
4.23
4.23
4.24
4.25
4.25
4.26
7.26
7.38
7.38
7.39
7.40
7.41
7.42
7.44
7.45
7.45
7.66
7.67
7.67
7.67
7.68
7.68
Cresswell, Eey and Denmark S184NATURE CHEMISTRY | www.nature.com/naturechemistry 184© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
19.2
20.8
26.9
29.5
30.5
60.0
63.1
66.1
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
127.7
129.
613
3.8
133.
813
5.6
Cresswell, Eey and Denmark S185NATURE CHEMISTRY | www.nature.com/naturechemistry 185© 2015 Macmillan Publishers Limited. All rights reserved
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
9.02
2.92
0.99
2.00
0.97
2.00
0.96
0.96
6.15
4.05
1.06
1.62
1.63
1.66
1.67
1.67
1.68
1.69
1.70
1.72
1.77
1.78
1.79
1.80
1.81
1.82
1.84
1.86
1.88
1.88
1.90
2.14
2.15
2.16
2.16
2.17
2.18
2.19
2.20
2.21
3.67
3.68
3.69
3.70
3.72
3.73
3.74
3.75
3.97
3.97
3.98
3.99
3.99
4.00
4.01
4.07
4.09
4.10
4.11
4.13
7.26
7.38
7.38
7.39
7.41
7.42
7.43
7.44
7.44
7.45
7.45
7.66
7.67
7.67
7.68
7.68
7.68
Cresswell, Eey and Denmark S186NATURE CHEMISTRY | www.nature.com/naturechemistry 186© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
19.2
21.9
26.8
29.1
31.7
60.2
63.0
67.2
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
127.
612
9.6
133.
713
3.8
135.
5
Cresswell, Eey and Denmark S187NATURE CHEMISTRY | www.nature.com/naturechemistry 187© 2015 Macmillan Publishers Limited. All rights reserved
-3-2-10123456789101112f1 (ppm)
20.9
9
1.05
1.03
1.04
1.01
2.03
1.00
0.97
2.03
0.97
0.97
3.00
2.00
1.03
1.04
1.05
1.06
1.07
1.08
1.09
1.09
1.11
1.60
1.61
1.62
1.63
1.64
1.65
1.75
1.76
1.77
1.78
1.81
1.83
1.85
1.86
1.87
1.88
1.89
1.90
1.91
2.03
2.04
2.05
2.05
2.06
2.07
2.08
2.09
2.15
2.16
2.17
2.18
2.19
2.20
2.20
2.21
2.22
2.71
2.72
2.73
2.74
2.75
2.77
2.90
2.91
2.92
2.93
2.94
2.95
2.96
3.68
3.69
3.70
3.72
3.73
3.74
3.75
3.76
4.01
4.01
4.02
4.02
4.03
4.04
4.11
4.11
4.12
4.12
4.13
4.14
7.20
7.21
7.22
7.22
7.23
7.26
7.29
7.31
7.32
Cresswell, Eey and Denmark S188NATURE CHEMISTRY | www.nature.com/naturechemistry 188© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
12.0
18.0
29.9
31.4
32.7
36.2
62.6
64.6
65.5
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
126.
212
8.5
128.
5
140.
5
Cresswell, Eey and Denmark S189NATURE CHEMISTRY | www.nature.com/naturechemistry 189© 2015 Macmillan Publishers Limited. All rights reserved
-2.0-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
0.99
1.13
2.04
1.01
2.02
1.00
0.99
2.02
0.99
0.99
3.01
2.02
1.38
1.61
1.62
1.63
1.64
1.64
1.65
1.66
1.67
1.80
1.81
1.82
1.83
1.85
1.86
1.87
1.88
1.89
1.90
1.91
1.92
2.00
2.01
2.02
2.03
2.03
2.04
2.05
2.05
2.07
2.07
2.13
2.13
2.14
2.15
2.16
2.17
2.18
2.19
2.20
2.21
2.22
2.22
2.24
2.25
2.25
2.70
2.72
2.73
2.74
2.75
2.76
2.90
2.91
2.92
2.93
2.94
2.95
2.96
3.66
3.67
3.67
3.68
3.69
3.69
3.70
3.71
4.00
4.01
4.01
4.02
4.03
4.03
4.06
4.07
4.08
4.08
4.09
4.10
7.21
7.22
7.22
7.23
7.26
7.29
7.31
7.32
Cresswell, Eey and Denmark S190NATURE CHEMISTRY | www.nature.com/naturechemistry 190© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
29.7
31.1
32.6
36.0
62.1
64.5
65.4
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
126.
212
8.5
128.
5
140.
4
Cresswell, Eey and Denmark S191NATURE CHEMISTRY | www.nature.com/naturechemistry 191© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.07
3.07
1.02
1.02
1.03
1.01
3.08
1.00
1.25
1.26
1.28
1.58
1.60
1.99
2.00
2.01
2.01
2.02
2.03
2.03
2.04
2.05
2.05
2.06
2.07
2.25
2.25
2.26
2.27
2.27
2.28
2.29
2.30
2.31
2.31
2.46
2.48
2.50
2.51
2.53
2.56
2.57
2.58
2.59
2.60
2.61
2.61
2.62
4.09
4.09
4.10
4.11
4.11
4.12
4.14
4.15
4.16
4.23
4.24
4.25
4.25
4.26
4.27
4.27
4.28
7.26
Cresswell, Eey and Denmark S192NATURE CHEMISTRY | www.nature.com/naturechemistry 192© 2015 Macmillan Publishers Limited. All rights reserved
-100102030405060708090100110120130140150160170180190200f1 (ppm)
14.2
20.8
29.2
31.1
59.8
60.6
65.1
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
172.
6
Cresswell, Eey and Denmark S193NATURE CHEMISTRY | www.nature.com/naturechemistry 193© 2015 Macmillan Publishers Limited. All rights reserved
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
2.00
1.98
4.01
2.08
1.01
1.02
0.98
2.05
1.00
0.84
0.85
0.85
0.86
0.87
0.88
0.97
0.98
0.99
1.00
1.00
1.58
1.59
1.59
1.60
1.61
1.62
1.63
1.63
1.72
1.73
1.74
1.75
1.76
1.78
1.79
1.79
1.81
1.81
1.82
1.83
1.84
1.85
1.86
1.92
1.93
1.93
1.94
1.95
1.95
1.96
1.97
1.97
1.98
1.99
1.99
2.01
2.01
2.02
2.02
2.03
2.04
2.04
2.05
2.06
2.06
2.07
4.01
4.02
4.03
4.04
4.04
4.05
4.07
4.09
4.10
4.11
4.11
4.12
4.13
4.14
4.15
4.16
4.23
4.24
4.25
4.25
4.26
4.27
4.27
4.28
7.26
Cresswell, Eey and Denmark S194NATURE CHEMISTRY | www.nature.com/naturechemistry 194© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
8.4
12.8
20.6
26.0
30.3
59.8
63.5
65.5
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
174.
8
Cresswell, Eey and Denmark S195NATURE CHEMISTRY | www.nature.com/naturechemistry 195© 2015 Macmillan Publishers Limited. All rights reserved
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
2.98
1.00
1.00
1.00
0.98
2.00
2.02
2.01
1.00
0.97
5.31
1.56
1.58
1.68
1.69
1.70
1.70
1.71
1.71
1.72
1.73
1.83
1.84
1.85
1.85
1.87
1.87
1.89
1.91
1.93
1.94
1.96
1.97
2.05
2.06
2.07
2.08
2.09
2.10
2.88
2.91
2.91
2.94
3.69
3.70
3.72
3.72
3.73
3.74
3.75
3.77
3.87
3.89
3.89
3.90
3.90
3.91
3.92
4.00
4.01
4.02
4.02
4.03
4.04
4.21
4.21
4.22
4.23
4.23
4.24
4.25
4.25
7.21
7.22
7.23
7.25
7.26
7.28
7.28
7.29
7.29
7.30
Cresswell, Eey and Denmark S196NATURE CHEMISTRY | www.nature.com/naturechemistry 196© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
20.6
27.9
34.6
43.9
59.9
65.2
65.3
66.2
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
110.
8
126.
512
8.0
130.
5
136.
4
Cresswell, Eey and Denmark S197NATURE CHEMISTRY | www.nature.com/naturechemistry 197© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.00
1.02
1.01
1.02
1.00
3.01
0.98
0.99
1.00
1.00
1.57
1.58
1.90
1.91
1.91
1.92
1.93
1.94
1.95
1.96
1.97
2.04
2.05
2.06
2.06
2.07
2.08
2.09
2.09
2.10
2.11
2.33
2.34
2.36
2.37
2.49
2.49
2.50
2.51
2.52
2.52
2.52
2.53
2.54
3.73
3.97
3.97
3.98
3.99
3.99
4.00
4.21
4.22
4.23
4.23
4.24
4.25
4.25
4.26
5.88
5.88
5.89
5.91
5.91
5.92
6.90
6.92
6.92
6.93
6.94
6.95
6.95
6.96
Cresswell, Eey and Denmark S198NATURE CHEMISTRY | www.nature.com/naturechemistry 198© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
20.5
29.1
31.9
51.5
59.7
64.8
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
122.
2
147.
0
166.
7
Cresswell, Eey and Denmark S199NATURE CHEMISTRY | www.nature.com/naturechemistry 199© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
8.95
3.01
2.14
1.04
1.06
1.98
0.99
1.00
2.01
3.02
2.01
1.50
1.57
1.59
1.62
1.63
1.64
1.65
1.66
1.68
1.69
1.70
1.71
1.72
1.72
1.74
1.74
1.75
1.76
1.79
1.80
1.80
1.81
1.81
1.82
1.83
1.85
1.85
1.86
1.87
1.89
1.90
1.90
1.91
1.92
1.92
1.93
1.94
1.94
1.95
1.95
1.96
3.22
3.24
3.25
3.27
3.28
4.08
4.09
4.10
4.11
4.12
4.23
4.24
4.24
4.25
4.25
4.26
4.27
4.28
4.42
4.45
4.47
4.51
7.28
7.29
7.30
7.30
7.31
7.31
7.35
7.35
7.37
7.38
7.38
Cresswell, Eey and Denmark S200NATURE CHEMISTRY | www.nature.com/naturechemistry 200© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
0.8
CD3C
N1.
0 CD
3CN
1.2
CD3C
N1.
3 CD
3CN
1.5
CD3C
N1.
7 CD
3CN
1.8
CD3C
N
21.8
21.8
26.0
28.9
28.9
28.9
28.9
32.9
47.0
51.2
61.6
68.4
80.2
117.
9
128.
112
8.5
129.
5
140.
1
156.
6
Cresswell, Eey and Denmark S201NATURE CHEMISTRY | www.nature.com/naturechemistry 201© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.00
2.02
2.01
2.00
0.99
0.99
2.02
2.02
1.60
1.61
1.77
1.79
1.81
1.83
1.84
1.86
1.99
2.01
2.02
2.03
2.04
2.04
2.06
3.72
3.73
3.74
3.97
3.97
3.98
4.00
4.00
4.05
4.06
4.07
4.09
4.10
7.26
7.70
7.71
7.71
7.72
7.72
7.73
7.83
7.83
7.84
7.84
7.85
7.85
7.86
Cresswell, Eey and Denmark S202NATURE CHEMISTRY | www.nature.com/naturechemistry 202© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
22.0
25.4
32.1
37.1
60.0
66.3
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
123.
3
132.
013
4.0
168.
3
Cresswell, Eey and Denmark S203NATURE CHEMISTRY | www.nature.com/naturechemistry 203© 2015 Macmillan Publishers Limited. All rights reserved
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)
2.91
9.09
1.19
1.14
1.07
1.11
1.00
1.01
1.02
1.00
6.18
4.03
0.96
0.97
0.99
1.07
1.43
1.44
1.45
1.47
1.49
1.50
1.51
1.53
1.53
1.54
1.55
1.56
1.56
1.57
1.57
1.57
1.58
1.59
1.60
1.60
1.61
1.63
1.78
1.79
1.80
1.80
1.81
1.82
1.82
1.83
1.84
1.85
1.89
1.90
1.90
1.91
1.92
1.93
1.94
1.95
1.96
3.82
3.83
3.84
3.85
3.96
3.98
3.98
4.00
4.05
4.06
4.06
4.07
4.07
4.08
4.08
4.46
4.46
4.47
4.47
4.47
4.48
4.49
4.49
7.26
7.38
7.39
7.39
7.40
7.42
7.44
7.44
7.45
7.47
7.47
7.47
7.65
7.65
7.67
7.67
7.67
7.69
7.69
Cresswell, Eey and Denmark S204NATURE CHEMISTRY | www.nature.com/naturechemistry 204© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
13.4
19.2
19.8
26.8
37.6
61.2
63.7
64.9
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
127.
812
7.8
129.
913
2.7
133.
013
5.5
135.
6
Cresswell, Eey and Denmark S205NATURE CHEMISTRY | www.nature.com/naturechemistry 205© 2015 Macmillan Publishers Limited. All rights reserved
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)
3.05
9.19
1.06
0.99
0.99
0.99
1.00
2.00
0.99
6.34
4.10
0.95
0.96
0.98
1.08
1.42
1.43
1.44
1.44
1.45
1.46
1.46
1.47
1.48
1.49
1.49
1.62
1.63
1.64
1.64
1.65
1.66
1.67
1.68
1.69
1.69
1.74
1.75
1.76
1.77
1.78
1.79
1.80
1.81
1.82
1.91
1.91
1.92
1.93
1.93
1.94
1.94
1.95
1.95
1.95
1.96
1.97
1.97
3.89
3.91
3.92
3.93
4.07
4.08
4.08
4.09
4.09
4.10
4.34
4.34
4.35
4.36
4.36
4.37
4.38
7.26
7.39
7.39
7.40
7.41
7.42
7.44
7.44
7.44
7.45
7.46
7.46
7.47
7.47
7.47
7.69
7.69
7.69
7.70
7.70
7.71
7.71
7.71
Cresswell, Eey and Denmark S206NATURE CHEMISTRY | www.nature.com/naturechemistry 206© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
13.5
19.2
19.3
26.7
35.9
61.7
65.1
65.2
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
127.
812
9.9
132.
813
2.9
135.
613
5.6
Cresswell, Eey and Denmark S207NATURE CHEMISTRY | www.nature.com/naturechemistry 207© 2015 Macmillan Publishers Limited. All rights reserved
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
5.99
9.01
1.01
1.01
1.01
1.01
1.00
1.00
1.01
1.00
3.02
2.08
0.05
0.84
2.05
2.06
2.07
2.07
2.08
2.09
2.10
2.11
2.12
2.25
2.26
2.27
2.28
2.29
2.30
2.31
2.32
2.33
2.74
2.76
2.77
2.77
2.79
2.80
2.88
2.89
2.89
2.90
2.91
2.92
2.93
3.76
3.77
3.78
3.79
3.85
3.87
3.87
3.89
3.99
4.00
4.00
4.01
4.01
4.02
4.03
4.27
4.28
4.28
4.28
4.29
4.30
4.30
4.30
7.19
7.21
7.22
7.26
7.28
7.29
7.31
Cresswell, Eey and Denmark S208NATURE CHEMISTRY | www.nature.com/naturechemistry 208© 2015 Macmillan Publishers Limited. All rights reserved
-100102030405060708090100110120130140150160170180190200f1 (ppm)
-5.5
-5.5
18.1
25.7
32.5
37.4
60.4
64.0
64.3
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
126.
212
8.5
128.
5
140.
4
Cresswell, Eey and Denmark S209NATURE CHEMISTRY | www.nature.com/naturechemistry 209© 2015 Macmillan Publishers Limited. All rights reserved
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
2.99
1.08
1.08
2.00
1.00
1.00
1.00
0.99
0.97
0.94
0.96
0.97
1.39
1.40
1.42
1.43
1.45
1.46
1.47
1.49
1.54
1.56
1.57
1.59
1.60
1.61
1.63
1.84
1.85
1.85
1.87
1.87
1.88
2.06
2.08
2.09
3.86
3.87
3.88
3.90
3.90
3.93
3.94
3.95
3.96
3.98
4.15
4.15
4.16
4.17
4.17
4.18
4.22
4.23
4.24
4.24
4.25
4.25
4.26
7.26
Cresswell, Eey and Denmark S210NATURE CHEMISTRY | www.nature.com/naturechemistry 210© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
13.4
19.8
37.2
61.7
64.5
65.4
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
Cresswell, Eey and Denmark S211NATURE CHEMISTRY | www.nature.com/naturechemistry 211© 2015 Macmillan Publishers Limited. All rights reserved
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
3.02
0.14
1.00
1.12
0.14
2.00
2.01
0.06
3.23
2.11
2.14
2.16
2.17
2.18
2.19
2.20
2.21
2.22
2.23
2.24
2.25
2.26
2.27
2.28
2.68
2.69
2.70
2.73
2.75
2.76
2.77
2.79
2.90
2.90
2.91
2.92
2.93
2.94
2.95
2.96
3.69
3.70
3.71
3.85
3.86
3.87
3.88
3.89
3.90
3.92
3.93
3.94
3.95
4.14
4.14
4.15
4.17
4.18
4.18
4.19
4.20
4.20
4.21
5.79
5.80
5.82
7.22
7.23
7.25
7.26
7.31
7.32
7.34
Cresswell, Eey and Denmark S212NATURE CHEMISTRY | www.nature.com/naturechemistry 212© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
32.5
33.0
36.3
36.8
58.7
61.0
64.4
65.4
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
126.
312
6.4
127.7
128.
512
8.6
128.
813
7.0
140.
214
0.3
Cresswell, Eey and Denmark S213NATURE CHEMISTRY | www.nature.com/naturechemistry 213© 2015 Macmillan Publishers Limited. All rights reserved
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
1.01
2.01
0.06
0.99
1.03
0.05
2.00
2.00
0.02
3.12
2.01
2.06
2.07
2.08
2.09
2.14
2.15
2.16
2.17
2.18
2.19
2.20
2.21
2.23
2.23
2.24
2.25
2.26
2.27
2.53
2.69
2.70
2.73
2.74
2.75
2.76
2.77
2.79
2.90
2.91
2.92
2.93
2.94
2.95
2.96
3.70
3.85
3.86
3.87
3.89
3.90
3.91
3.92
3.93
3.94
3.96
4.14
4.14
4.15
4.16
4.17
4.17
4.18
4.19
4.19
4.20
4.21
5.80
7.22
7.23
7.23
7.25
7.26
7.30
7.32
7.33
Cresswell, Eey and Denmark S214NATURE CHEMISTRY | www.nature.com/naturechemistry 214© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
32.5
36.8
61.0
64.4
65.4
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
126.
312
8.5
128.
6
140.
2
Cresswell, Eey and Denmark S215NATURE CHEMISTRY | www.nature.com/naturechemistry 215© 2015 Macmillan Publishers Limited. All rights reserved
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
0.99
2.01
0.02
0.99
1.01
0.02
2.00
2.00
0.00
2.99
1.98
2.04
2.05
2.06
2.14
2.16
2.17
2.19
2.19
2.22
2.24
2.25
2.27
2.67
2.69
2.70
2.73
2.74
2.75
2.77
2.79
2.90
2.91
2.92
2.93
2.95
2.96
3.69
3.70
3.71
3.85
3.87
3.88
3.89
3.90
3.91
3.92
3.93
3.94
3.96
4.14
4.14
4.15
4.16
4.16
4.17
4.17
4.18
4.19
4.19
4.20
4.20
5.79
5.80
5.82
7.21
7.23
7.24
7.26
7.30
7.32
7.33
Cresswell, Eey and Denmark S216NATURE CHEMISTRY | www.nature.com/naturechemistry 216© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170f1 (ppm)
32.5
36.8
61.0
64.4
65.4
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
126.
312
8.5
128.
6
140.
2
Cresswell, Eey and Denmark S217NATURE CHEMISTRY | www.nature.com/naturechemistry 217© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
0.99
1.01
1.00
1.00
1.00
2.00
2.01
3.09
2.00
1.94
1.95
1.96
2.05
2.06
2.07
2.08
2.09
2.10
2.11
2.13
2.40
2.41
2.43
2.44
2.46
2.46
2.74
2.76
2.76
2.77
2.78
2.78
2.79
2.80
2.94
2.94
2.95
2.96
2.97
2.98
2.99
4.00
4.01
4.02
4.02
4.07
4.07
4.09
4.09
4.10
4.12
4.12
7.21
7.22
7.23
7.26
7.30
7.31
7.33
Cresswell, Eey and Denmark S218NATURE CHEMISTRY | www.nature.com/naturechemistry 218© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
31.8
36.6
60.8
64.4
66.3
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
126.
212
8.5
128.
5
140.
4
Cresswell, Eey and Denmark S219NATURE CHEMISTRY | www.nature.com/naturechemistry 219© 2015 Macmillan Publishers Limited. All rights reserved
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
0.11
2.02
0.99
0.36
1.26
1.00
1.98
1.99
0.25
0.11
3.42
2.29
1.97
1.98
1.99
2.08
2.09
2.10
2.11
2.13
2.40
2.41
2.43
2.44
2.46
2.46
2.53
2.54
2.56
2.58
2.72
2.75
2.76
2.77
2.77
2.79
2.79
2.81
2.94
2.95
2.96
2.97
2.98
2.99
3.00
4.01
4.01
4.08
4.08
4.10
4.10
4.11
4.11
4.12
4.13
4.16
4.17
5.82
5.83
5.85
7.20
7.21
7.23
7.24
7.26
7.29
7.30
7.32
7.33
Cresswell, Eey and Denmark S220NATURE CHEMISTRY | www.nature.com/naturechemistry 220© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
29.7
31.8
34.4
36.6
60.8
64.4
66.3
66.8
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
124.
112
6.0
126.
212
6.2
128.
312
8.4
128.
512
8.5
133.
7
140.
414
1.1
Cresswell, Eey and Denmark S221NATURE CHEMISTRY | www.nature.com/naturechemistry 221© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
1.25
1.00
2.63
4.71
2.16
1.00
1.05
2.70
2.70
2.04
12.1
4
2.20
2.21
2.22
2.23
2.24
2.26
2.27
3.76
3.77
3.78
3.79
3.79
3.81
3.83
3.85
3.85
3.86
3.87
3.88
3.90
3.91
3.92
3.93
3.93
3.95
3.97
3.97
3.98
3.99
4.00
4.00
4.01
4.02
4.03
4.03
4.04
4.05
4.06
4.28
4.29
4.30
4.31
4.31
4.34
4.35
4.36
4.36
4.37
4.38
4.38
4.39
4.39
4.40
4.40
4.41
4.42
4.42
4.43
4.43
4.44
4.45
4.59
4.62
4.63
4.65
7.26
7.30
7.32
7.33
7.35
7.36
7.37
7.39
Cresswell, Eey and Denmark S222NATURE CHEMISTRY | www.nature.com/naturechemistry 222© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
58.4
59.3
61.9
62.9
64.1
64.1
64.1
70.6
70.8
73.6
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
127.7
127.
812
7.9
128.
012
8.5
128.
513
7.2
137.
3
Cresswell, Eey and Denmark S223NATURE CHEMISTRY | www.nature.com/naturechemistry 223© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
0.97
2.01
2.03
1.00
1.01
2.00
5.02
2.20
2.21
2.22
3.85
3.86
3.87
3.88
3.90
3.91
3.92
3.93
3.97
3.98
3.98
3.99
4.00
4.01
4.01
4.02
4.03
4.04
4.05
4.05
4.06
4.28
4.29
4.30
4.31
4.32
4.34
4.35
4.36
4.37
4.38
4.59
4.62
4.63
4.65
7.30
7.30
7.31
7.32
7.33
7.33
7.36
7.37
7.39
Cresswell, Eey and Denmark S224NATURE CHEMISTRY | www.nature.com/naturechemistry 224© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
59.3
62.9
64.2
70.9
73.6
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
127.7
127.
912
8.5
137.
3
Cresswell, Eey and Denmark S225NATURE CHEMISTRY | www.nature.com/naturechemistry 225© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
11.5
8
2.00
0.54
0.54
3.08
0.24
3.15
1.97
7.95
5.15
1.05
1.51
1.53
1.53
1.55
1.57
1.78
1.79
1.80
1.82
1.90
1.90
1.93
1.93
1.99
2.00
2.02
2.03
2.03
2.04
2.05
2.05
2.06
2.06
2.07
2.08
2.09
2.11
2.12
2.13
2.29
2.31
2.32
2.34
2.36
3.45
3.48
3.49
3.51
3.59
3.61
7.26
7.36
7.36
7.37
7.37
7.38
7.40
7.42
7.42
7.43
7.44
7.44
7.45
7.63
7.63
7.65
7.66
7.66
Cresswell, Eey and Denmark S226NATURE CHEMISTRY | www.nature.com/naturechemistry 226© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
19.3
19.3
26.8
26.9
29.8
30.7
35.3
38.1
57.1
58.6
65.7
69.5
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
127.
512
7.6
129.
512
9.6
133.
713
4.1
135.
5
Cresswell, Eey and Denmark S227NATURE CHEMISTRY | www.nature.com/naturechemistry 227© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5f1 (ppm)
5.00
1.41
2.00
0.23
0.30
1.02
1.11
0.34
3.84
2.48
1.06
1.99
2.00
2.01
2.02
2.06
2.07
2.08
2.10
2.20
2.22
2.23
2.24
2.25
2.27
2.28
2.30
2.31
2.34
2.36
2.62
2.63
2.64
2.66
2.68
2.69
2.70
3.56
3.57
3.68
3.70
4.27
4.28
4.29
4.36
4.37
4.38
7.26
7.37
7.39
7.40
7.42
7.42
7.43
7.45
7.62
7.63
7.64
7.65
7.65
7.66
7.67
Cresswell, Eey and Denmark S228NATURE CHEMISTRY | www.nature.com/naturechemistry 228© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
19.2
6
26.8
326
.88
35.7
235
.94
36.7
837
.69
62.3
163
.34
66.2
167
.92
76.7
4 CD
Cl3
77.0
0 CD
Cl3
77.2
5 CD
Cl3
127.
6512
7.74
129.
6412
9.77
133.
3313
3.64
135.
5313
5.54
Cresswell, Eey and Denmark S229NATURE CHEMISTRY | www.nature.com/naturechemistry 229© 2015 Macmillan Publishers Limited. All rights reserved
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
9.16
2.59
1.18
1.20
0.79
1.11
2.00
0.37
0.54
6.10
3.98
1.05
1.06
1.58
1.60
1.61
1.62
1.64
1.65
1.66
1.76
1.77
1.79
1.80
1.81
2.04
2.13
2.14
2.16
2.17
2.47
2.49
2.50
3.65
3.66
3.67
3.69
3.70
5.55
5.56
5.58
5.63
5.64
5.65
5.67
7.17
7.26
7.37
7.39
7.40
7.42
7.43
7.45
7.65
7.66
7.66
7.66
7.67
7.67
7.68
7.68
Cresswell, Eey and Denmark S230NATURE CHEMISTRY | www.nature.com/naturechemistry 230© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
13.9
19.2
20.7
25.1
26.8
29.7
30.1
32.0
62.6
62.8
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
122.
512
7.3
127.
612
7.6
129.
612
9.6
133.
813
3.9
133.
913
5.5
Cresswell, Eey and Denmark S231NATURE CHEMISTRY | www.nature.com/naturechemistry 231© 2015 Macmillan Publishers Limited. All rights reserved
-3-2-10123456789101112f1 (ppm)
9.33
0.96
1.72
1.19
1.31
0.87
1.14
2.00
0.42
0.55
6.34
4.14
1.05
1.06
1.61
1.63
1.64
1.66
1.67
1.69
1.69
1.70
1.70
1.77
1.79
1.80
1.81
1.81
1.83
2.06
2.06
2.23
2.24
2.26
2.27
2.43
2.44
2.46
3.66
3.66
3.67
3.67
3.68
3.68
5.39
5.39
5.41
5.41
5.42
5.42
5.48
5.49
5.51
5.52
7.26
7.37
7.37
7.38
7.40
7.41
7.42
7.42
7.43
7.43
7.44
7.44
7.65
7.66
7.67
7.67
7.68
7.69
Cresswell, Eey and Denmark S232NATURE CHEMISTRY | www.nature.com/naturechemistry 232© 2015 Macmillan Publishers Limited. All rights reserved
0102030405060708090100110120130140150160170180190200f1 (ppm)
14.0
19.2
19.2
25.2
26.1
26.1
26.9
30.4
31.5
35.8
62.5
63.4
76.7
CDC
l377
.0 C
DCl3
77.3
CDC
l3
120.
112
5.4
127.
612
7.6
129.
512
9.5
133.
913
4.0
135.
213
5.5
135.
6
Cresswell, Eey and Denmark S233NATURE CHEMISTRY | www.nature.com/naturechemistry 233© 2015 Macmillan Publishers Limited. All rights reserved