ligand- and brønsted acid/base-switchable reaction

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Ligand- and Brønsted Acid/Base-Switchable Reaction Pathways in

Gold(I)-Catalyzed Cycloisomerizations of Allenoic Acids

Sachin Handa,a Sri S. Subramanium,a Aaron A. Ruch,a,b Joseph M. Tanskic and LeGrande M. Slaughter*a,b

aDepartment of Chemistry, Oklahoma State University, Stillwater, Oklahoma 74078

bDepartment of Chemistry, University of North Texas, Denton, TX 76203

cDepartment of Chemistry, Vassar College, Poughkeepsie, New York 12604

*[email protected]

SUPPLEMENTARY INFORMATION

Synthesis of allenoic acid substrates p. S2

X-ray crystallographic data and procedures p. S12

References p. S16

Kinetic plots P. S17

1H and 13C NMR spectra p. S27

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2015

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SYNTHESIS OF ALLENOIC ACID SUBSTRATES (1a-k)

Substrates 1a and 1j were synthesized by literature procedures.1 Substrates 1b and 1c

were synthesized by a modified procedure starting from the corresponding cycloalkanones

(Schemes S1 and S2).2 Substrates 1d-i and 1k were synthesized according to Scheme S2,2,3

starting from allenic esters 14a1a or 14b. Pd(PPh3)4 (min. 99.5%, min. 9% wt/wt Pd) was

purchased from Chem-Impex International, Inc.

Scheme S1. Synthesis of precursors to allenoic acid substrates.

Scheme S2. Synthesis of allenoic acid substrates.

1-(3-((tert-Butyldimethylsilyl)oxy)prop-1-yn-1-yl)cyclopentanol (10b). To a well-

dried two neck round-bottom flask equipped with a septum and nitrogen balloon, 70 mL dry

THF and tert-butyldimethyl(prop-2-yn-1-yloxy)silane (5.0 g, 29 mmol) were added. The

reaction mixture was cooled to −78 °C, and then 11.7 mL of nBuLi (2.5 M in hexanes; 29 mmol)

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was added slowly over 5 min via syringe. The reaction mixture was stirred for 10 min at −78 °C.

Cyclopentanone (2.60 mL, 29.4 mmol) was then slowly added to the reaction mixture over 2

min. The reaction mixture was stirred for 30 min at −78 °C and then for an additional 50 min at

25 °C. The reaction mixture was quenched with 0.5 M aqueous NH4Cl and then extracted twice

with 100 mL of diethyl ether. The organic layer was separated and dried over anhydrous sodium

sulfate. The solvent was removed on a rotary evaporator to obtain a viscous oil, which was

purified by flash column chromatography on silica. Rf 0.45 (1:9 diethyl ether/hexanes); colorless

oil, yield 7.0 g (94%). 1H NMR (400 MHz, CDCl3): δ 4.35 (s, 2H), 2.04 (br. s, 1H, OH), 1.89-

1.82 (m, 2H), 1.72-1.59 (m, 2H), 1.58-1.46 (m, 4H), 0.90 (s, 9H), 0.12 (s, 6H) ppm. 13C NMR

(101 MHz, CDCl3): δ 88.6, 81.9, 74.6, 51.9, 42.4, 26.0, 23.5, −4.9 ppm. IR (neat): ν 3274, 2359,

1104, 1070 cm-1. HRMS (ESI-orbitrap, [C14H26O2Si + H]+) calcd 255.1780, found m/z

255.1784.

1-(3-((tert-Butyldimethylsilyl)oxy)prop-1-yn-1-yl)cycloheptanol (10c). To a well-

dried two neck round-bottom flask equipped with a septum and nitrogen balloon, 50 mL dry

THF and tert-butyldimethyl(prop-2-yn-1-yloxy)silane (5.0 g, 29 mmol) were added. The

reaction mixture was cooled to −78 °C, and then 11.7 mL of nBuLi (2.5 M in hexanes; 29 mmol)

was added slowly over 5 min via syringe. The reaction mixture was stirred for 45 min at −78 °C.

Cycloheptanone (3.50 mL, 29.7 mmol) was then slowly added to the reaction mixture over 2

min. The reaction mixture was stirred for 1 h at −78 °C and then for an additional 2 h at 25 °C.

The reaction mixture was quenched with 0.5 M aqueous NH4Cl and then extracted twice with

100 mL of diethyl ether. The organic layer was separated and dried over anhydrous sodium

sulfate. The solvent was removed on a rotary evaporator to obtain a viscous oil. After further

drying under high vacuum, an analytically pure white solid was obtained. White solid, m.p. 62-

63 °C, yield 7.40 g (89%). 1H NMR (400 MHz, CDCl3): δ 4.35 (s, 2H), 2.01 (d, J = 8.0 Hz, 1H),

1.98 (d, J = 8.0 Hz, 1H), 1.85-1.77 (m, 3H), 1.67-1.49 (m, 7H), 0.91 (s, 9H), 0.12 (s, 6H). 13C

NMR (101 MHz, CDCl3): δ 89.7, 82.1, 71.8, 51.9, 43.2, 28.3, 25.9, 22.3, −4.9. IR (neat): ν

3272, 2358, 1101, 1071 cm-1. HRMS (ESI-orbitrap, [C16H30O2Si + H]+) calcd 283.2093, found

m/z 283.2101.

tert-Butyldimethyl[(3-(1-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentyl)prop-2-yn-1-

yl)oxy]silane (11b). To a solution of 10b (3.17 g, 12.4 mmol) in 5 mL of dry dichloromethane

was added TsOH·H2O (12 mg, 0.063 mmol), and the reaction mixture was stirred for 10 min at 0

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°C. 3,4-Dihydro-2H-pyran (8.8 mL, 96 mmol) was then added, and the reaction mixture was

stirred for 12 h at 25 °C. The reaction mixture was quenched with 5 mL of NEt3 and then stirred

for an additional 20 min at 25 °C. The solvent was evaporated to obtain a viscous yellow oil.

The crude material was dissolved in 200 mL of diethyl ether and then washed sequentially with

0.5 M NaHCO3, 0.05 M cold HCl, and water. The organic layer was separated and dried over

anhydrous sodium sulfate. The solvent was again removed, and the crude product was purified

by flash chromatography on silica. Rf 0.55 (1:19 diethyl ether/hexanes); viscous yellow oil, yield

3.37 g (80%). 1H NMR (400 MHz, CDCl3): δ 5.04 (dd, J = 5.6, 3.2 Hz, 1H), 4.35 (s, 2H), 3.94-

3.89 (m, 1H), 3.53-3.47 (m, 1H), 2.24-2.18 (m, 1H), 2.00-1.47 (m, 13H), 0.91 (s, 9H), 0.12 (s,

6H). 13C NMR (101 MHz, CDCl3): δ 96.7, 86.6, 83.3, 81.0, 63.6, 52.0, 41.4, 40.0, 32.1, 25.9,

25.6, 23.4, 23.0, 20.5, 18.4, −4.9. IR (neat): ν 3276, 2368, 1111, 1070 cm-1. HRMS (ESI-

orbitrap, [C19H34O3Si + H]+) calcd 339.2355, found m/z 339.2361.

tert-Butyldimethyl[(3-(1-((tetrahydro-2H-pyran-2-yl)oxy)cycloheptyl)prop-2-yn-1-

yl)oxy]silane (11c). This compound was synthesized from 10c (10.0 g, 35.4 mmol) by the same

procedure used to prepare 11b. Rf 0.67 (1:19 diethyl ether/hexanes); viscous yellow oil, yield

9.34 g (72%). 1H NMR (400 MHz, CDCl3): δ 5.05 (dd, J = 6.4, 3.6 Hz, 1H), 4.36 (s, 2H), 3.96-

3.91 (m, 1H), 3.50-3.46 (m, 1H), 2.02-1.95 (m, 3H), 1.89-1.82 (m, 2H), 1.71-1.45 (m, 13H), 0.90

(s, 9H), 0.12 (s, 6H). 13C NMR (101 MHz, CDCl3): δ 96.0, 87.4, 83.8, 78.4, 63.7, 51.9, 42.2,

40.8, 32.4, 28.8, 25.9, 25.6, 22.2, 22.0, 20.7, 18.3, −4.9. IR (neat): ν 3277, 2357, 1101, 1076 cm-

1. HRMS (ESI-orbitrap,[C21H38O3Si + H]+) calcd 367.2668, found m/z 367.2667.

3-[1-((Tetrahydro-2H-pyran-2-yl)oxy)cyclopentyl]prop-2-yn-1-ol (12b). To a

solution of 11b (3.94 g, 11.6 mmol) in 50 mL of THF was added [nBu4N]F (3.34 g, 12.8 mmol),

and the reaction mixture was stirred for 12 h at 25 °C. After complete consumption of the

starting material as monitored by TLC, the reaction mixture was diluted with 100 mL of ethyl

acetate and then washed thoroughly with water. The organic layer was separated and dried over

anhydrous sodium sulfate. The crude material was purified by column chromatography on silica.

Rf 0.48 (1:4 acetone/hexanes); viscous yellow oil, yield 1.8 g (69%). 1H NMR (400 MHz,

CDCl3): δ 5.05 (dd, J = 4.8, 3.2 Hz, 1H), 2.28 (d, J = 6.4 Hz, 2H), 3.95-3.89 (m, 1H), 3.54-3.49

(m, 1H), 2.37-2.30 (m, 1H), 2.22-2.15 (m, 1H), 2.01-1.88 (m, 2H), 1.85-1.75 (m, 4H), 1.74-1.64

(m, 3H), 1.58-1.48 (m, 4H). 13C NMR (101 MHz, CDCl3): δ 96.3, 87.4, 83.0, 80.7, 63.3, 51.2,

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41.2, 40.3, 32.0, 25.5, 23.4, 23.0, 20.1. IR (neat): ν 3312, 3257, 2359, 1103, 1066 cm-1. HRMS

(ESI, [C13H20O3 + Na]+) calcd 247.1310, found m/z 247.1313.

3-[1-((Tetrahydro-2H-pyran-2-yl)oxy)cycloheptyl]prop-2-yn-1-ol (12c). This

compound was synthesized from 11c (11.6 g, 31.7 mmol) by the same procedure used to prepare

12b. Rf 0.50 (1:4 acetone/hexanes); viscous yellow oil, yield 6.0 g (75%). 1H NMR (400 MHz,

CDCl3): δ 5.08 (dd, J = 5.2, 3.6 Hz, 1H), 4.30 (s, 2H), 3.98-3.92 (m, 1H), 3.53-3.47 (m, 1H),

2.11 (br. s, 1H, OH), 2.06-1.95 (m, 2H), 1.96 (d, J = 7.6 Hz, 1H), 1.90-1.79 (m, 2H), 1.72-1.57

(m, 3H), 1.56-1.46 (m, 10H). 13C NMR (101 MHz, CDCl3): δ 95.7, 88.6, 83.5, 78.1, 63.3, 51.3,

42.0, 41.2, 32.3, 28.7, 28.2, 25.6, 22.3, 22.1, 19.3. IR (neat): ν 3311, 3258, 2358, 1101, 1066

cm-1. HRMS (ESI-orbitrap, [C15H24O3 + Na]+) calcd 275.1623, found m/z 275.1630.

3-Cyclopentylideneprop-2-en-1-ol (13b). A well-dried 500 mL two-neck round bottom

flask was fitted with a condenser topped with a nitrogen balloon, and 200 mL of dry THF was

added by syringe. The flask contents were cooled to 0 °C under inert atmosphere, and LiAlH4

(2.33 g, 61.6 mmol) was added under nitrogen counterflow. The slurry was stirred for 5 min,

and then a solution of 12b (6.9 g, 31 mmol) in 20 mL of dry THF was added dropwise via

syringe. The reaction mixture was allowed to warm to 25 °C and then heated at reflux for 45

min. The mixture was then cooled to 0 °C, and the unreacted LiAlH4 was quenched with 5.0 M

NaOH. The quenched mixture was stirred for 30 min at 25 °C and then diluted with 200 mL of

diethyl ether and filtered through celite. The organic layer was dried over anhydrous sodium

sulfate. The solvent was removed on a rotary evaporator to obtain analytically pure material as a

colorless oil. Rf 0.38 (1:4 acetone/hexanes); colorless oil, yield 2.8 g (73%). 1H NMR (400

MHz, CDCl3): δ 5.33-5.26 (m, 1H), 4.08 (d, J = 5.2 Hz, 2H), 2.40-2.36 (m, 4H), 1.71-1.65 (m,

4H), 1.55 (br s, 1H, OH). 13C NMR (151 MHz, CD2Cl2): δ 196.4, 107.1, 92.7, 61.3, 31.7, 27.4.

IR (neat) ν 3311 (m), 1961 (w), 1901 (w) cm-1. HRMS (ESI, [C8H12O + H]+) calcd 125.0966,

found m/z 125.0954.

3-Cycloheptylideneprop-2-en-1-ol (13c). This compound was synthesized from 12c

(4.0 g, 16 mmol) by the same procedure used to prepare 13b. Rf 0.39 (1:4 acetone/hexanes);

colorless oil, yield 1.8 g (75%). 1H NMR (400 MHz, CDCl3): δ 5.20-5.16 (m, 1H), 4.06 (t, J =

6.0 Hz, 2H), 2.27-2.24 (m, 4H), 1.65-1.51 (m, 8H). 13C NMR (101 MHz, CDCl3): δ 200.7,

108.0, 89.7, 61.2, 32.6, 29.4, 28.6. HRMS (ESI-orbitrap, [C10H16O + Na]+) calcd 175.1099,

found m/z 175.1101.

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3-Cyclopentylideneallyl benzoate (14b). This compound was prepared by a

modification of literature procedures used to prepare 14a.1a Under dry conditions, a solution of

allenol 13b (1.90 g, 15.2 mmol) in 50 mL of dry CH2Cl2 was placed in a two-necked round

bottom flask. The solution was cooled to 0 °C, and pyridine (1.4 mL, 17 mmol) and a catalytic

amount of DMAP (186 mg, 1.52 mmol) were added followed by slow syringe addition of

benzoyl chloride (2.6 mL, 22 mmol). The reaction mixture was then warmed to RT and stirred

for an additional 12 h. After complete consumption of starting material as monitored by TLC,

the solvent was evaporated under reduced pressure. The resulting oily residue was dissolved in

50.0 mL CH2Cl2 and then sequentially washed with cold 0.5 M HCl (2 x 50 mL) and saturated

aqueous NaHCO3. The organic layer was separated and dried over anhydrous sodium sulfate.

The solvent was removed under reduced pressure to obtain a pale yellow viscous oil, which was

purified by flash column chromatography on silica. Rf 0.52 (8:92 diethyl ether/hexanes); yellow

oil, yield 3.13 g (90%). 1H NMR (400 MHz, CDCl3): δ 8.08-8.05 (m, 2H), 7.57-7.53 (m, 1H),

7.35 (dt, J = 7.6, 1.6 Hz, 2H), 5.35-5.28 (m, 1H), 4.79 (d, J = 6.8 Hz, 2H), 2.40-2.36 (m, 4H),

1.67-1.61 (m, 4H). 13C NMR (101 MHz, CDCl3): δ 198.8, 166.5, 133.0, 130.1, 129.7, 128.4,

106.1, 87.4, 63.8, 31.3, 27.1. IR (neat): 2958 (m), 2867 (m), 1972 (w), 1715 (s), 1450 (m) cm-

1. HRMS (ESI-orbitrap, [C15H16O2 + H]+) calcd 229.1229, found m/z 229.1222.

3-Cycloheptylideneallyl benzoate (14c). This compound was prepared from 13c (1.30

g, 8.51 mmol) by the same procedure used to synthesize 14b. The compound was highly

unstable over silica and was used immediately after moderate purification. Rf 0.56 (8:92 diethyl

ether/hexanes); colorless oil, yield 1.95 g (89%). 1H NMR (400 MHz, CDCl3): δ 8.08-8.06 (m,

2H), 7.55-7.53 (m, 1H), 7.43 (dt, J = 8.0, 1.6 Hz, 2H), 5.24-5.19 (m, 1H), 4.77 (d, J = 6.4 Hz,

2H), 2.29-2.24 (m, 4H), 1.63-1.57 (m, 4H), 1.54-1.49 (m, 4H). 13C NMR (101 MHz, CDCl3): δ

203.3, 166.5, 132.9, 130.6, 129.8, 128.4, 106.9, 84.7, 63.9, 32.3, 29.4, 28.4. IR (neat): 3068

(w), 2923 (m), 2850 (m), 1960 (w), 1717 (s), 1601 (w), 1584 (w), 1451 (m). HRMS (ESI-

orbitrap, [C17H20O2 + H]+) calcd 257.1542, found m/z 257.1551.

General procedure for the synthesis of 2,2-diaryl allene methyl esters (15b-i,k). A

modification of literature procedures was used.1a,4 Into an oven-dried 100 mL, two-neck round

bottom flask containing the corresponding methyl diarylacetate56 (1.0 equiv relative to 14) was

added 50.0 mL of dry THF via vacuum distillation. The reaction mixture was cooled to −78 °C,

and lithium hexamethyldisilazide (1.18 g, 7.08 mmol) was added under argon counterflow. The

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reaction mixture was stirred at −78 °C under argon for approximately 2 h. Meanwhile, 100 mL

of dry THF was distilled under vacuum into another oven-dried 250 mL two-neck round bottom

flask, and a solution of 14 (3.0-5.0 mmol) in dry THF was added via syringe followed by

addition of Pd(PPh3)4 (5 mol%). This mixture was stirred at room temperature for 2 h, then

cooled to −78 °C and transferred via cannula into the vessel containing the cold (−78 °C)

solution of lithiated methyldiaryl acetate. The resulting mixture was allowed to warm slowly to

room temperature and stirred for 12 h. The mixture was then diluted with 100 mL of ethyl

acetate and sequentially washed with 0.5 M NaHCO3 and water. The organic layer was

separated and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced

pressure to obtain the crude product, which was purified by flash column chromatography on

silica.

Methyl-5-cyclopentylidene-2,2-diphenylpent-4-enoate (15b). Because of inseparable

impurities, compound was used as obtained for the next step without further purification.

Viscous oil, yield 1.12 g (82%). 1H NMR (400 MHz, CDCl3): δ 7.34-7.23 (m, 10H), 7.87-7.79

(m, 1H), 3.70 (s, 3H), 3.10 (d, J = 7.2 Hz, 2H), 2.15-2.11 (m, 4H), 1.59-1.54 (m, 4H).

Methyl-5-cycloheptylidene-2,2-diphenylpent-4-enoate (15c). Rf 0.55 (1:9

acetone/hexanes); yellow viscous oil, yield 0.95 g (89%). 1H NMR (400 MHz, CDCl3): δ 7.32-

7.22 (m, 10H), 4.75-4.69 (m, 1H), 3.70 (s, 3H), 3.10 (d, J = 7.2 Hz, 2H), 2.12-1.99 (m, 4H),

1.55-1.46 (m, 8H). 13C NMR (101 MHz, CDCl3): δ 203.9, 174.7, 142.6, 129.2, 127.9, 126.8,

103.8, 84.3, 60.7, 52.5, 39.6, 32.2, 29.4, 28.5. HRMS (ESI-orbitrap, [C25H28O2 + H]+) calcd

361.2167, found m/z 361.2165.

Methyl-2,2-bis(4-chlorophenyl)-5-cyclohexylidenepent-4-enoate (15d). Rf 0.59 (1:9


7.24 (m, 4H), 7.21-7.18 (m, 4H), 4.68-4.63 (m, 1H), 3.70 (s, 3H), 3.03 (d, J = 7.2 Hz, 2H), 1.88-

1.87 (m, 4H), 1.53-1.44 (m, 6H). 13C NMR (101 MHz, CDCl3): δ 200.8, 173.9, 140.8, 133.1,

130.6, 128.2, 102.3, 83.83, 59.9, 52.7, 39.5, 31.2, 27.4, 26.1. HRMS (ESI, [C24H24Cl2O2 + H]+)

calcd 415.1232, found m/z 415.1228.

Methyl-2,2-bis(4-chlorophenyl)-5-cyclopentylidenepent-4-enoate (15e). Rf 0.56 (1:9


7.23 (m, 4H), 7.19-7.15 (m, 4H), 4.79-4.72 (m, 1H), 3.68 (s, 3H), 3.01 (d, J = 7.6 Hz, 2H), 2.15-

2.08 (m, 4H), 1.58-1.55 (m, 4H). 13C NMR (101 MHz, CDCl3): δ 199.6, 173.9, 140.8, 133.1,

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130.5, 128.2, 103.7, 86.5, 59.8, 52.7, 39.2, 31.0, 27.1. HRMS (ESI, [C23H22Cl2O2 + Na]+) calcd

423.0895, found m/z 423.0889.

Methyl-5-cyclohexylidene-2,2-bis(2,3-dihydrobenzofuran-5-yl)pent-4-enoate (15f).

Rf 0.49 (3:7 ethyl acetate/hexanes); yellow viscous oil, yield 1.75 g (82%). 1H NMR (400 MHz,

CDCl3): δ 7.12-7.11 (m, 2H), 7.01 (dd, J = 8.8, 1.6 Hz, 2H), 6.69 (d, J = 8.4, Hz, 2H), 4.71-4.67

(m, 1H), 4.55 (t, J = 8.8 Hz, 4H), 3.69 (s, 3H), 3.16 (t, J = 8.8 Hz, 4H), 3.02 (d, J = 7.6 Hz, 2H),

1.94-1.92 (m, 4H), 1.55-1.44 (m, 6H). 13C NMR (101 MHz, CDCl3): δ 200.5, 175.4, 158.9,

135.1, 129.0, 126.5, 125.8, 108.5, 101.8, 84.9, 71.5, 59.7, 52.4, 40.2, 31.3, 30.0, 27.5, 26.3.

HRMS (ESI, [C28H30O4 + Na]+) calcd 453.2042, found m/z 453.2036.

Methyl-5-cyclopentylidene-2,2-bis(2,3-dihydrobenzofuran-5-yl)pent-4-enoate (15g).

Rf 0.45 (3:7 ethyl acetate/hexanes); yellow viscous oil, yield 1.12 g (79%). 1H NMR (400 MHz,

CDCl3): δ 7.12-7.11 (m, 2H), 7.01 (dd, J = 8.4, 1.6 Hz, 2H), 6.69 (d, J = 8.4 Hz, 2H), 4.84-4.78

(m, 1H), 4.56 (t, J = 8.8 Hz, 4H), 3.69 (s, 3H), 3.17 (t, J = 8.8 Hz, 4H), 3.02 (d, J = 7.6 Hz, 2H),

2.20-2.16 (m, 4H), 1.61-1.57 (m, 4H). 13C NMR (101 MHz, CDCl3): δ 199.3, 175.4, 158.9,

135.1, 128.9, 126.5, 125.8, 108.4, 103.1, 87.5, 71.5, 59.7, 52.4, 39.8, 30.9, 30.0, 27.1. HRMS

(ESI, [C27H28O4 + Na]+) calcd 439.1885, found m/z 439.1880.

Methyl-9-(3-cyclohexylideneallyl)-9H-xanthene-9-carboxylate (15h). Rf 0.48 (1:9


7.20 (m, 2H), 7.16 (dd, J = 7.6, 1.2 Hz, 2H), 7.07-7.01 (m, 4H), 4.41-4.36 (m, 1H), 3.59 (s, 3H),

2.95 (d, J = 7.6 Hz, 2H), 1.61-1.53 (m, 4H), and 1.36-1.27 (m, 6H). 13C NMR (101 MHz,

CDCl3): δ 201.2, 174.5, 150.8, 134.0, 133.8, 128.6, 127.3, 123.2, 121.4, 116.7, 101.9, 82.5, 52.9,

50.5, 42.1, 31.1, 27.3, 26.1. HRMS (ESI, [C24H24O3 + Na]+) calcd 383.1623, found m/z

383.1622.

Methyl-9-(3-cyclopentylideneallyl)-9H-xanthene-9-carboxylate (15i). Rf 0.46 (1:9


7.16 (m, 4H), 7.06-7.01 (m, 4H), 4.61-4.53 (m, 1H), 3.58 (s, 3H), 2.99 (d, J = 6.8 Hz, 2H), 1.92-

1.83 (m, 2H), 1.71-1.62 (m, 2H), 1.45-1.41 (m, 4H). 13C NMR (101 MHz, CDCl3): δ 199.7,

174.4, 150.8, 134.0, 133.8, 128.6, 127.2, 123.3, 121.5, 116.7, 103.8, 85.3, 52.9, 50.2, 41.0, 30.7,

26.9. HRMS (ESI, [C23H22O3 + Na]+) calcd 369.1467, found m/z 369.1464.

Methyl-5-cyclohexylidene-2-(3-methoxyphenyl)-2-phenylpent-4-enoate (15k). Due to

inseparable impurities, the compound was only moderately purified by flash column

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chromatography and was used as such for the next step. Rf 0.55 (3:7 diethyl ether/hexanes);

yellow viscous oil, yield 1.12 g (70%; per 1H NMR). 1H NMR (400 MHz, CDCl3): δ 7.33-7.18

(m, 6H), 6.86-6.75 (m, 3H), 4.74-4.68 (m, 1H), 3.73 (s, 3H), 3.68 (s, 3H), 3.11-3.01 (m, 2H),

1.88-1.86 (m, 4H), 1.51-1.41 (m, 6H).

2-(3-Methoxyphenyl)-2-phenylacetic acid (16). This compound was prepared

according to the literature procedure via the corresponding diaryl acetonitrile.6a,6b Full

characterization data of 16 have not been previously reported. Rf 0.39 (4:19 diethyl

ether/hexanes); colorless oil, yield 1.98 g (93%). 1H NMR (400 MHz, CDCl3): δ 11.1 (br. s, 1H,

COOH), 7.34-7.23 (m, 6H), 6.92 (dd, J = 7.6, 0.8 Hz, 1H), 6.88 (t, J = 2.0 Hz, 1H), 6.82 (ddd, J

= 8.0, 2,8, 0.8 Hz, 1H), 5.02 (s, 1H), 3.77 (s, 3H). 13C NMR (101 MHz, CDCl3): δ177.8, 159.9,

139.5, 137.9, 129.8, 129.5, 128.8, 127.7, 121.2, 114.8, 112.9, 57.0, 55.4. IR (neat): 3045, 2955

cm-1. HRMS (ESI, [C15H14O3 + Na]+) calcd 265.0841, found m/z 265.0844.

Methyl-2-(3-methoxyphenyl)-2-phenylacetate (17). The compound was prepared from

16 via Fischer esterification. Analytical data were in agreement with the literature.6c,7

General procedure for synthesis of allenoic acid substrates (1b-i,k). Into a 100 mL

two-neck round bottom flask fitted with a condenser was added a solution of allene ester 15 (2.1

– 2.9 mmol) in 30 mL of ethanol. Aqueous 2.0 M NaOH (30 mL) was added, and the reaction

mixture was heated at reflux for 12 h. The reaction mixture was then cooled to 25 °C and diluted

with 20 mL of water. This mixture was washed with 50 mL of hexanes. The aqueous layer was

separated and washed twice more with 10 mL portions of hexanes. The aqueous layer was

neutralized with 0.5 M HCl to obtain a turbid solution containing the desired compound. The

aqueous layer was extracted twice with CH2Cl2 (15 mL). The organic layer was separated and

dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to

obtain the crude product, which was purified by flash column chromatography on silica.

5-Cyclopentylidene-2,2-diphenylpent-4-enoic acid (1b).3 Rf 0.35 (1:4 ethyl

acetate/hexanes); white crystalline solid, m.p. 153-154 °C (reported1b 129-132 °C), yield 0.80 g

(89%). Spectroscopic data were in agreement with the literature.1b

5-Cycloheptylidene-2,2-diphenylpent-4-enoic acid (1c). Rf 0.55 (1:4 ethyl

acetate/hexanes); white crystalline solid, m.p. 68-69 °C, yield 0.78 g (81%). 1H NMR (400

MHz, CDCl3): δ 11.1 (br s, 1H, COOH), 7.34-7.23 (m, 10H), 4.74-4.69 (m, 1H), 3.08 (d, J = 7.6

Hz, 2H), 2.09-1.95 (m, 4H), 1.51-1.43 (m, 8H). 13C NMR (101 MHz, CDCl3): δ.204.1, 179.3,

S10

142.1, 129.4, 129.2, 128.0, 127.1, 104.0, 84.0, 60.6, 39.4, 32.1, 29.5, 28.5. IR (neat): ν 2919

(m), 2952 (m), 1960 (w), 1759 (s) 1689 (s), 1495 (m) cm-1. HRMS (ESI-orbitrap, [C24H26O2 +

Na]+) calcd 369.1830, found m/z 369.1820.

2,2-Bis(4-chlorophenyl)-5-cyclohexylidenepent-4-enoic acid (1d). Rf 0.57 (1:4 ethyl

acetate/hexanes); white crystalline solid, m.p. 157-158 °C, yield 0.80 g (87%). 1H NMR (400

MHz, CDCl3): δ 11.4 (br. s, 1H, COOH), 7.27-7.20 (m, 8H), 4.67-4.63 (m, 1H), 3.00 (d, J = 7.2

Hz, 2H), 1.90-1.78 (m, 4H), 1.46-1.39 (m, 6H). 13C NMR (101 MHz, CDCl3): δ 201.0, 179.1,

140.2, 133.4, 130.7, 128.3, 102.6, 83.6, 59.8, 39.3, 31.1, 27.3, 26.1. IR (neat): ν 3062 (br), 2918

(m), 2851 (w), 1965 (w), 1690 (s), 1490 (s) cm-1. HRMS (ESI-orbitrap, [C23H22Cl2O2 + Na]+)

calcd 423.0894, found m/z 423.0896.

2,2-Bis(4-chlorophenyl)-5-cyclopentylidenepent-4-enoic acid (1e).3 Rf 0.53 (1:4 ethyl

acetate/hexanes); white crystalline solid, m.p. 122-124 °C (decomp), yield 0.80 g (88%). 1H

NMR (400 MHz, CDCl3): δ 11.1 (br. s, 1H, COOH), 7.27-7.19 (m, 8H), 4.79-4.73 (m, 1H), 3.00

(d, J = 7.2 Hz, 2H), 2.12-2.05 (m, 4H), 1.57-1.51 (m, 4H). 13C NMR (101 MHz, CDCl3): δ

199.8, 178.8, 140.2, 133.4, 130.7, 128.3, 103.9, 86.3, 59.7, 39.1, 30.9, 27.0. IR (neat): ν 3060

(br), 2917 (m), 2853 (w), 1962 (w), 1691 (s), 1491 (s) cm-1. HRMS (ESI-orbitrap, [C22H20Cl2O2

+ Na]+) calcd 409.0738, found m/z 409.0738.

5-Cyclohexylidene-2,2-bis(2,3-dihydrobenzofuran-5-yl)pent-4-enoic acid (1f). Rf

0.33 (3:2 ethyl acetate/hexanes); viscous yellow oil, yield 0.70 g (66%). 1H NMR (400 MHz,

CDCl3): δ 10.5 (br. s, 1H, COOH), 7.21-7.05 (m, 4H), 6.71-6.66 (m, 2H), 4.73-4.68 (m, 1H),

4.59-4.51 (m, 4H), 3.23-3.13 (m, 4H), 3.03-2.88 (m, 2H), 1.97-1.89 (m, 4H), 1.52-1.41 (m, 6H). 13C NMR (101 MHz, CDCl3): δ.200.7, 159.1, 134.5, 129.1, 126.6, 125.9, 108.5, 102.0, 84.6,

71.5, 59.5, 40.1, 31.3, 30.0, 27.5, 26.3. IR (neat): ν 3033 (br), 2919 (m), 2855 (w), 1969 (w),

1699 (s), 1491 (s) cm-1. HRMS (ESI-orbitrap, [C27H28O4 + Na]+) calcd 439.1885, found m/z

439.1883.

5-Cyclopentylidene-2,2-bis(2,3-dihydrobenzofuran-5-yl)pent-4-enoic acid (1g). Rf

0.36 (3:2 ethyl acetate/hexanes); viscous yellow oil, yield 0.55 g (65%). 1H NMR (400 MHz,

CDCl3): δ 11.2 (br. s, 1H, COOH), 7.16-7.12 (m, 2H), 7.06 (dt, J = 8.4, 2.0 Hz, 2H), 6.70 (d, J =

8.8, Hz, 2H), 4.84-4.79 (m, 1H), 4.56 (t, J = 8.8 Hz, 4H), 3.17 (t, J = 8.8 Hz, 4H), 3.02 (d, J = 7.2

Hz, 2H), 2.16 (sextet, J = 3.2 Hz, 4H), 1.61-1.56 (m, 4H). 13C NMR (101 MHz, CDCl3): δ

199.5, 159.1, 134.5, 129.1, 126.6, 126.0, 126.0, 108.5, 103.3, 87.3, 71.5, 59.5, 39.7, 30.9, 30.0,

S11

27.1. IR (neat): ν 2959 (br), 2921 (m), 2856 (w), 1968 (w), 1697 (s), 1490 (s) cm-1. HRMS

(ESI-orbitrap, [C26H26O4 + Na]+) calcd 425.1729, found m/z 425.1730.

9-(3-Cyclohexylideneallyl)-9H-xanthene-9-carboxylic acid (1h).3 Rf 0.53 (1:4 ethyl

acetate/hexanes); white solid, m.p. 64-65 °C, yield 0.80 g (80%). 1H NMR (400 MHz, CDCl3): δ

11.2 (br s, 1H, COOH), 7.24-7.20 (m, 4H), 7.06-7.00 (m, 4H), 4.43-4.39 (m, 1H), 2.92 (d, J =

6.8 Hz, 2H), 1.61-1.49 (m, 4H), 1.38-1.24 (m, 6H). 13C NMR (101 MHz, CDCl3): δ 201.2,

179.0, 150.9, 128.9, 127.6, 123.3, 120.8, 116.8, 102.1, 82.5, 50.2, 40.8, 31.0, 27.2, 26.1. IR

(neat): ν 3055 (br), 2971(m), 2919 (m), 2865 (w), 1965 (w), 1901(w) 1698 (s), 1481 (m) cm-1.

HRMS (ESI-orbitrap, [C23H22O3 + Na]+) calcd 369.1467, found m/z 369.1465.

9-(3-Cyclopentylideneallyl)-9H-xanthene-9-carboxylic acid (1i).3 Rf 0.55 (1:4 ethyl

acetate/hexanes); white solid, m.p. 62-63 °C, yield 0.55 g (76%). 1H NMR (400 MHz, CDCl3): δ

10.8 (br. s, 1H, COOH), 7.27-7.21 (m, 4H), 7.07-7.03 (m, 4H), 4.61-4.54 (m, 1H), 2.99 (d, J =

6.8 Hz, 2H), 1.88-1.82 (m, 2H), 1.63-1.57 (m, 2H), 1.45-1.40 (m, 4H). 13C NMR (101 MHz,

CDCl3): δ 199.8, 178.5, 150.9, 129.0, 127.4, 123.3, 120.7, 116.8, 104.1, 85.2, 49.9, 39.5, 30.7,

26.9. IR (neat): ν 3053 (br), 2970 (m), 2921 (m), 2866 (w), 1961 (w), 1901 (w) 1696 (s), 1480

(m) cm-1. HRMS (ESI, [C22H20O3 + Na]+) calcd 355.1310, found m/z 355.1313.

5-Cyclohexylidene-2-(3-methoxyphenyl)-2-phenylpent-4-enoic acid (1k). Rf 0.41 (1:4

ethyl acetate/hexanes); white solid, m.p. 134-135 °C, yield 0.78 g (84%). 1H NMR (400 MHz,

CDCl3): δ 10.7 (br. s, 1H, COOH), 7.32-7.18 (m, 6H), 6.90 (ddd, J = 8.4, 2.4 Hz, 1H), 6.86 (t, J

= 2.0 Hz, 1H), 6.77 (ddd, J = 8.4, 2.4, 0.8 Hz, 1H), 4.73-4.69 (m, 1H), 3.72 (s, 3H), 3.11-3.01

(m, 2H), 1.89-1.81 (m, 4H), 1.49-1.39 (m, 6H). 13C NMR (101 MHz, CDCl3): δ 200.8, 179.3,

159.3, 143.7, 141.9, 129.3, 128.9, 127.9, 127.1, 121.8, 115.9, 112.0, 102.1, 84.3, 60.6, 55.3, 39.5,

31.2, 27.4, 26.2. IR (neat): ν 2918 (br), 2589 (w), 1699 (s), 1750 (s), 1612 (m) cm-1. HRMS

(ESI, [C24H26O3 + H]+) calcd 363.1960, found m/z 363.1956.

S12

X-RAY CRYSTALLOGRAPHIC DATA AND PROCEDURES

General Considerations. X-ray diffraction data were collected on Bruker single crystal

diffractometers equipped with CCD detectors (APEX or APEX II) using a combination of and

scans. Unit cell determination and data collection utilized the Bruker SMART8 and APEX29

software packages. Data integration employed SAINT.10 Multiscan absorption corrections were

implemented using SADABS.11 Structures were solved by direct methods and refined by full-

matrix least-squares on F2 using the SHELXTL software suite.12 Non-hydrogen atoms were

assigned anisotropic temperature factors, and hydrogen atoms were included in calculated

positions (riding model) with isotropic U fixed at 1.5 times the Ueq of the attached atom for -CH3

groups and 1.2 times the Ueq of the attached atom for other hydrogen atoms. CCDC 997310-

997312 contain the supplementary crystallographic data for this paper. These data can be

obtained free of charge from The Cambridge Crystallographic Data Center via

www.ccdc.cam.ac.uk/data_request/cif.

Figure S1. X-ray structure of 2a, with displacement ellipsoids drawn at the 50% probability

level

X-ray Crystallographic Analysis of 2a. Colorless blocks were obtained by slow diffusion of

pentane into a Et2O/CH2Cl2 (98:2) solution of 2a. A sample measuring 0.40 x 0.25 x 0.25 mm

was placed on the goniometer of an APEX II DUO diffractometer, and reflection data were

collected using radiation from a Cu IS microfocus X-ray source (=1.54178 Å). The sample

was cooled to 125(1) K during data collection using an Oxford Cryostream liquid nitrogen

cooling device. C23H24O2, Mr = 332.42 g mol-1, monoclinic, space group P21/c, a = 10.2882(1),

S13

b = 10.0834(1), c = 17.6278(2) Å, = 100.1728(4)°, V = 1799.96(3) Å3, Z = 4, Z´ = 1, calcd =

1.227 g cm-3, = 0.598 mm-1, T = 125(2) K, 2max = 133.19°, 26227 total reflections, 3169

independent (Rint = 0.024), 3122 observed [I > 2(I)]. Final R1 [I > 2(I)] = 0.0345, wR2 (all

data) = 0.0844, largest difference peak (hole) 0.284 (-0.203) e Å-3. CCDC 997310.

(a) (b)

(c)

Figure S2. Views of the X-ray structure of 4a, showing the two crystallographically

independent molecules (a,b) and the asymmetric unit (c). Displacement ellipsoids are drawn at

the 50% probability level

X-ray Crystallographic Analysis of 4a. Colorless needles were obtained by slow diffusion of

pentane into a CH2Cl2/Et2O solution (98:2) of 4a. A sample measuring 0.24 x 0.07 x 0.02 mm

was placed on the goniometer of an APEX II DUO diffractometer, and reflection data were

collected using graphite-monochromated radiation from a Mo sealed-tube X-ray source

(=0.71073 Å) equipped with a MonoCap waveguide collimator. The sample was cooled to

125(1) K during data collection using an Oxford Cryostream liquid nitrogen cooling device. By

analyzing reflection data with CELL_NOW13 and TWINABS,14 the crystal was modeled as a

two-component nonmerohedral twin. Final refinement was performed on both twin components

S14

using data in HKLF5 format. The refined proportion of twin components was 0.477(1):0.523(1),

with a twin law corresponding to a 180 degree rotation about reciprocal axis 0.031 1.000 -0.005

and real axis 0.003 1.000 0.000. The asymmetric unit contains two crystallographically

independent molecules. C23H24O2, Mr = 332.42 g mol-1, triclinic, space group Pī, a = 7.1469(5),

b = 15.303(1), c = 16.4534(10) Å, = 73.1224(1), = 89.797(1), = 88.864(1)°, V = 1799.96(3)

Å3, Z = 4, Z´ = 2, calcd = 1.282 g cm-3, = 0.080 mm-1, T = 125(2) K, 2max = 61.02°, 22822

total reflections, 10426 independent (Rint = 0.086), 9443 observed [I > 2(I)]. Final R1 [I >

2(I)] = 0.0626, wR2 (all data) = 0.1600, largest difference peak (hole) 0.382 (-0.335) e Å-3.

CCDC 997311.

Figure S3. X-ray structure of 9, with displacement ellipsoids drawn at the 50% probability

level. Only the major orientation of the disordered phenyl group (C17-C21) is shown.

X-ray Crystallographic Analysis of 9. Colorless plates were obtained by slow diffusion of

pentane into a Et2O/CH2Cl2 (9:1) solution of 9. A sample measuring 0.52 x 0.40 x 0.02 mm was

placed on the goniometer of a SMART APEX diffractometer, and reflection data were collected

using graphite-monochromated radiation from a Mo sealed-tube X-ray source (=0.71073 Å)

equipped with a MonoCap waveguide collimator. The sample was cooled to 100(1) K during

data collection using an Oxford Cryostream liquid nitrogen cooling device. The phenyl group

showed slight rotational disorder, which was treated with a two-part disorder model. The

occupancies for atoms C17 – C22 refined to 0.60(2) and 0.40(2) for the two phenyl ring

orientations indicated by unprimed and primed atoms, respectively. Restraints on the positional

S15

and displacement parameters of the disordered atoms were required. The COOH hydrogen

bonded to O25 was located on a difference map, and its position was allowed to refine freely.

C24H26O3, Mr = 362.45 g mol-1, triclinic, space group Pī, a = 9.7954(4), b = 9.8427(4), c =

11.0909(5) Å, = 78.548(2), = 77.234(2), = 64.389(2)°, V = 933.94(7) Å3, Z = 2, Z´ = 1,

calcd = 1.289 g cm-3, = 0.083 mm-1, T = 100(2) K, 2max = 50.5°, 17614 total reflections, 4626

independent (Rint = 0.015), 4139 observed [I > 2(I)]. Final R1 [I > 2(I)] = 0.0431, wR2 (all

data) = 0.1243, largest difference peak (hole) 0.422 (-0.182) e Å-3. CCDC 997312.

S16

REFERENCES

1. (a) J. L. Arbour, H. S. Rzepa, A. J. P. White and K. K. Hii, Chem. Commun., 2009, 7125; (b) J. L. Arbour, H. S. Rzepa, J. Contreras-García, L. A. Adrio, E. M. Barreiro and K. K. Hii, Chem. Eur. J., 2012, 18, 11317.

2. (a) S. Handa, Ph.D. Thesis, Oklahoma State University, 2013; (b) S. Handa, D. J. Lippincott, D. H. Aue and B. H. Lipshutz, Angew. Chem. Int. Ed., 2014, 53, 10658.

3. Syntheses of substrates 1b, 1e, 1h, and 1i by the same procedures were recently reported (ref 2b).

4. J. Löfstedt, J. Franzén and J. E. Bäckvall, J. Org. Chem., 2001, 66, 8015. 5. Methyldiarylacetates with Ar = Ph and Ar2 = 9H-xanthen-9-yl were obtained from

commercial sources. Those with 4-chlorophenyl and 2,3-dihydrobenzofuran-5-yl substituents were prepared from the commercially available acids via Fischer esterification and used without chromatographic purification. The unsymmetrically substituted diaryl ester (17) used to synthesize 1k (Ar = Ph, Ar' = 3-methoxyphenyl) was prepared by literature procedures (refs 6a,b).

6. (a) T. Kametani, K. Kigasawa, M. Hiiragi, T. Aoyama and O. Kusama, J. Org. Chem., 1971, 36, 327; (b) T. Kametani, K. Kigasawa, M. Hiiragi and T. Aoyama, J. Med. Chem., 1971, 14, 1235; (c) G. Hilt and F. Galbiati, Synthesis, 2006, 3589.

7. C. P. Owens, A. Varela-Álvarez, V. Boyarskikh, D. G. Musaev, H. M. L. Davies and S. B. Blakey, Chem. Sci., 2013, 4, 2590.

8. SMART; Bruker AXS: Madison, WI, USA, 2007. 9. APEX2, Version 2.0; Bruker AXS: Madison, WI, USA, 2007. 10. SAINT; Bruker AXS: Madison, WI, USA, 2007. 11. Sheldrick, G. M. SADABS, Version 2.10; Bruker AXS Inc.: Madison, WI, USA, 2000. 12. Sheldrick, G. M. SHELXTL; Bruker AXS Inc.: Madison, WI, USA, 2008. 13. Sheldrick, G. M. CELL_NOW; Bruker AXS: Madison, WI, USA, 2004. 14. Sheldrick, G. M. TWINABS, Version 2008/2; Bruker AXS: Madison, WI, USA, 2008.

S17

KINETIC PLOTS

Pseudo first-order rate constant for 3a formation (incorporates catalyst concentration):

kobs = 2(2) x 10-4 min-1

S18


kobs = 2.3(2) x 10-3 min-1

S19

Pseudo zero-order rate constant for 2a formation (incorporates concentrations of catalyst and

1a): kobs = 11.4(7) mM min-1


kobs = 1.18(5) x 10-3 min-1

S20


1a): kobs = 17.5(2) mM min-1

S21


kobs = 2.7(2) x 10-3 min-1

S22


1a): kobs = 6.6(2) mM min-1

S23


kobs = 3.63(8) x 10-3 min-1

S24


kobs = 1.34(6) x 10-3 min-1

S25


kobs = 1.0(8) x 10-5 min-1

S26

(note: the left plot suggests a change in the catalyst after 50 min)


kobs = 1.37(6) x 10-3 min-1

S27

1H AND 13C NMR SPECTRA

6.10

4.00

1.00

1.00

0.950.94

9.67

1.481.501.511.531.541.552.062.082.092.112.122.142.152.162.172.652.682.682.713.003.013.033.045.045.055.065.075.085.085.095.105.195.217.217.227.227.237.237.247.287.287.297.307.307.317.317.327.347.357.367.367.367.377.387.387.397.407.40

1H NMR (400 MHz, CDCl3)


S28

8.00

3.97

1.00

1.01

0.97

0.94

9.67

1.491.511.521.531.551.571.581.592.242.252.252.272.292.642.662.672.703.033.043.063.075.025.035.045.055.055.065.075.255.255.255.275.275.277.227.237.247.287.297.307.307.317.317.327.327.347.357.367.367.367.377.377.387.387.397.397.417.41

27.32

28.70

29.09

29.67

30.56

37.88

44.49

58.35

73.84

76.83

77.15

77.35

77.46

122.33

127.25

127.53

127.81

127.85

128.46

129.08

139.88

142.42

150.34

177.37

127.25

127.53

127.81

127.85

128.46

129.08

13C NMR (101 MHz, CDCl3)

1H NMR

(400 MHz, CDCl3)

S29


26.55

27.92

28.36

29.77

37.13

44.46

57.56

73.43

76.84

77.16

77.48

118.46

128.76

128.84

129.18

129.43

138.21

140.32

149.31

176.62


6.28

4.00

1.00

1.02

0.970.96

7.91

1.481.521.531.541.541.561.592.092.112.12

2.602.622.632.662.922.932.962.97

5.025.035.045.045.055.055.065.085.165.187.207.217.227.227.237.247.257.257.267.277.297.297.307.327.337.337.347.35

S30

4.26

4.18

1.10

1.11

1.04

1.00

8.14

2.142.172.172.192.272.282.282.302.302.312.332.332.592.622.622.652.952.972.993.004.874.884.894.894.904.914.924.935.325.335.335.345.345.355.357.207.217.227.227.237.247.247.257.257.267.267.277.277.287.297.297.307.327.327.337.347.357.35

1.04

1.00

4.874.884.894.894.904.914.924.93

5.325.335.335.345.345.355.35

25.99

26.33

29.40

34.16

43.95

57.47

75.78

76.84

77.16

77.48

117.00

128.77

128.84

129.17

129.41

134.17

138.21

140.39

153.22

176.55



S31



S32

4.02

4.13

1.01

1.02

4.12

4.04

1.00

0.86

0.900.890.971.880.99

26.02

26.37

29.37

29.89

29.92

34.13

44.91

57.54

71.56

71.66

75.69

76.84

77.16

77.48

108.84

109.34

117.64

124.53

124.78

126.91

127.35

128.10

131.99

135.10

152.36

159.22

159.70

178.17



S33

6.28

3.052.05

1.00

0.94

0.98

8.17

1.531.541.551.571.581.591.601.611.612.132.142.152.162.182.222.252.262.282.692.712.722.747.127.137.147.147.147.157.167.167.167.177.187.187.187.187.197.207.217.227.227.247.247.257.267.267.277.287.297.307.307.307.317.327.337.337.347.35

26.58

27.96

28.39

29.81

37.15

50.32

50.80

73.82

76.84

77.16

77.48

116.73

117.64

119.04

122.86

123.69

124.11

124.33

125.87

127.45

129.00

129.28

148.82

151.01

151.70

177.33



S34

26.02

26.37

29.44

34.16

50.25

76.18

76.84

77.16

77.37

77.48

116.74

117.57

117.63

122.86

123.71

124.09

124.32

125.89

127.44

129.00

129.28

151.00

151.70

152.87

177.28

4.00

5.20

1.03

0.990.93

6.261.91

1.521.621.641.651.661.671.691.712.212.242.242.272.692.712.722.745.397.107.117.117.117.127.127.127.137.137.147.147.157.157.167.167.167.167.187.197.197.217.217.217.227.237.247.257.267.277.277.287.287.297.297.307.317.317.317.317.337.33



S35

6.75

4.11

1.00

1.00

0.890.97

2.67

0.874.51

1.551.561.572.102.112.122.142.152.172.182.632.652.662.672.672.682.692.713.013.013.023.033.043.053.053.063.753.785.095.105.205.226.876.876.886.886.906.946.956.967.027.027.207.227.247.267.287.307.307.317.327.337.357.377.397.407.407.42



S36

4.00

4.181.041.061.07

1.08

1.00

0.96

10.04

1.521.531.531.541.551.561.561.571.581.591.591.601.611.621.921.931.981.991.992.232.252.272.282.442.462.482.492.562.592.602.622.993.003.023.034.434.444.454.464.485.517.217.237.247.257.277.287.297.307.317.337.337.347.357.367.377.377.38

14.27

26.61

27.93

27.94

28.39

29.74

29.76

37.14

44.84

55.38

55.45

58.44

73.36

73.47

76.84

77.16

77.37

77.48

113.02

119.00

119.76

127.28

127.49

127.81

127.84

128.48

129.09

130.02

141.35

142.26

143.94

148.65

148.68

159.62

160.13

177.20

177.31



S37

22.28

22.90

25.36

29.02

43.60

43.69

58.18

76.16

76.84

77.16

77.48

125.18

127.25

127.48

127.77

127.83

128.46

129.02

129.06

132.71

139.95

142.38

177.29


S38

3a: HMQC 1H, 400 MHz

13C, 101 MHz

1H, 400 MHz 13C, 101 MHz

3a: HMBC

S39

2.20

4.321.112.15

1.11

1.00

0.91

10.37

1.841.861.871.881.901.922.272.292.312.312.332.342.352.352.442.452.472.492.602.622.632.642.652.662.673.043.063.083.094.504.514.534.545.507.247.247.257.257.267.267.277.297.307.317.317.327.337.347.347.357.367.377.387.397.407.417.417.50

23.49

32.59

35.67

36.76

43.71

58.19

76.03

76.84

77.16

77.48

127.25

127.44

127.62

127.76

127.80

128.45

129.00

138.78

140.01

142.33

177.14



S40

4.08

2.05

3.89

1.17

2.01

1.00

0.95

0.91

10.10

1.421.431.431.441.451.461.461.471.541.701.711.732.052.072.082.102.112.112.122.132.252.272.282.302.572.592.602.622.982.993.013.024.424.435.657.227.227.247.247.247.277.277.287.287.297.297.297.297.307.307.327.347.357.357.367.367.377.38

26.73

27.15

28.52

32.50

33.24

43.66

45.57

58.21

76.21

76.84

77.16

77.48

127.27

127.52

127.79

127.87

128.49

129.04

130.59

139.11

139.98

142.51

177.29



S41

4.37

3.96

0.96

2.01

1.07

1.00

0.90

7.88

1.531.541.551.551.561.571.581.591.591.601.611.621.621.631.641.921.942.002.002.242.252.272.292.452.472.492.502.532.552.562.582.932.942.962.974.424.434.454.465.527.227.227.237.247.257.267.277.277.287.287.297.307.327.337.337.357.357.36

0.96

2.01

1.07

2.242.252.272.292.452.472.492.502.532.552.562.58

2.932.942.962.97

22.26

22.89

25.37

29.04

43.40

43.49

57.28

76.23

76.84

77.16

77.48

125.46

128.76

128.80

129.16

129.35

132.47

133.59

134.12

138.23

140.40

176.51

125.46

128.76

128.80

129.16

129.35

132.47

133.59

134.12



S42

2.04

4.250.852.02

1.06

1.00

0.91

2.175.90

1.811.831.851.871.892.232.242.282.302.512.542.552.572.932.942.962.98

4.424.444.454.464.474.49

5.46

7.197.207.217.227.227.247.247.257.267.267.277.277.287.307.317.327.337.337.34

2.232.242.262.272.282.282.302.312.402.412.442.452.512.542.552.572.582.602.62



S43

4.11

4.39

0.92

2.12

1.07

4.00

1.024.18

1.00

1.96

1.09

3.01

1.531.551.561.571.571.581.591.601.601.611.631.941.992.222.242.262.272.442.452.482.492.502.512.542.902.912.932.953.133.163.183.204.414.434.444.514.544.554.564.574.595.526.686.706.746.766.966.966.986.987.087.097.107.117.137.167.187.19

22.34

22.97

25.41

29.11

29.88

29.92

43.66

44.47

57.40

71.56

71.66

76.15

76.84

77.15

77.36

77.47

124.49

124.76

125.13

126.93

127.36

128.05

132.11

132.87

135.14

159.24

159.69



S44

1.84

3.970.920.911.01

1.00

4.18

1.044.18

0.83

1.830.992.84

1.851.871.881.902.172.262.272.292.312.332.442.462.492.522.532.552.592.612.932.952.972.983.143.163.183.204.454.474.484.494.524.544.554.564.574.584.605.486.686.716.746.766.966.976.986.997.097.097.117.117.147.147.197.197.257.267.277.27



S45

4.05

4.05

2.09

0.89

1.00

0.99

0.96

8.28

1.471.481.491.511.541.561.571.952.272.292.302.332.342.362.382.392.462.472.492.502.522.742.762.782.79

4.974.985.01

5.557.147.157.167.167.187.187.207.247.267.297.317.317.317.337.337.347.357.357.37

21.78

22.37

24.73

28.30

38.89

39.10

39.31

39.52

39.73

39.94

40.15

43.22

47.97

48.60

76.47

116.26

116.86

122.38

123.00

124.08

124.31

124.40

126.43

127.82

129.17

129.40

132.76

149.41

150.34

176.82



S46

1.92

4.951.062.00

0.98

0.82

7.80

1.821.841.861.871.881.902.182.202.212.242.282.292.312.452.472.492.502.662.682.692.702.702.712.722.744.784.804.814.824.824.834.844.865.497.097.117.117.127.137.137.137.157.167.177.187.187.197.207.207.247.267.267.287.297.297.307.327.32

23.51

32.63

35.80

37.28

49.85

49.96

76.49

76.82

77.14

77.46

116.75

117.58

122.81

123.58

124.07

124.27

125.80

127.38

128.20

129.02

129.27

138.36

150.78

151.62

177.15



S47



OO

OMe

3k

OO

OMe

3k

S48


26.55

26.78

26.85

26.96

27.55

28.79

53.19

76.84

77.16

77.36

77.48

85.41

122.25

124.44

126.88

127.97

128.10

128.27

129.71

135.69

138.70

141.88

174.36


S49

0.903.073.021.060.891.13

2.00

1.00

0.90

0.950.995.78

1.541.711.711.721.741.741.751.771.771.811.831.841.861.881.882.002.022.162.182.192.452.462.482.492.512.512.532.542.542.892.916.636.657.167.167.187.187.207.207.267.277.277.297.297.317.317.407.417.427.437.437.447.457.477.477.487.497.50

1.541.711.721.741.741.751.771.831.841.861.882.182.192.492.512.512.532.542.91

26.27

26.59

27.28

27.89

27.90

30.54

42.19

53.52

76.84

77.16

77.48

85.74

122.28

124.20

127.01

127.97

128.19

128.26

129.70

135.73

139.61

141.51

174.54



S50

12.05

4.93

1.00

1.02

7.27

1.551.681.892.042.172.192.202.222.512.532.58

6.646.657.177.187.207.267.297.317.427.437.437.447.457.467.477.487.487.497.49

27.19

27.72

28.14

29.17

40.71

53.19

76.83

77.15

77.47

122.12

124.43

126.86

127.95

128.06

128.24

129.70

135.71

141.89

174.45



S51



OO

O

4f

O

S52



S53

3.033.032.121.131.111.062.071.071.08

3.05

1.001.032.382.77

0.66

1.281.311.341.361.371.431.451.461.491.491.511.521.631.641.661.881.891.901.911.932.022.032.042.262.572.602.602.612.622.792.802.882.893.826.816.817.117.117.227.237.237.247.247.257.267.267.277.277.287.287.297.297.307.307.317.317.327.32



S54

-4.90

18.44

23.54

25.98

42.40

51.95

74.63

76.84

77.16

77.48

81.95

88.60



S55



S56

5.99

9.21

4.747.191.941.05

1.14

1.17

2.14

1.00

0.12

0.91

3.473.483.503.513.533.903.903.91

4.35

5.035.035.045.05

7.26

-4.90

18.40

20.53

22.98

23.46

25.58

25.95

32.11

40.00

41.39

51.98

63.64

76.84

77.16

77.48

81.00

83.35

86.64

96.70



S57

6.01

9.93

8.105.152.483.37

1.20

1.28

2.18

1.00

-4.94

18.35

20.74

22.02

22.20

25.55

25.89

28.79

32.37

40.82

42.16

51.92

63.67

76.83

77.15

77.47

78.39

83.78

87.43

96.04



S58

4.363.334.272.101.170.96

1.14

1.11

2.10

1.00

1.501.511.521.541.551.551.561.671.681.681.691.701.701.711.711.721.721.721.731.741.741.751.761.771.771.781.791.791.801.801.811.811.821.831.831.841.851.911.921.931.951.961.971.972.162.182.193.503.523.533.924.284.295.045.055.055.067.26



S59

10.63

3.152.140.872.260.87

1.11

1.10

2.09

1.00

1.481.491.501.511.521.531.531.541.551.561.571.601.611.621.631.641.651.651.661.671.671.681.691.691.711.821.841.851.861.871.871.901.951.971.981.981.992.002.012.022.032.113.493.503.513.533.923.933.943.953.973.984.305.075.085.085.097.26

20.41

22.06

22.25

22.28

25.60

28.25

28.71

32.35

41.19

41.96

43.16

51.29

63.33

76.84

77.16

77.48

78.11

83.52

88.55

95.66



S60

8.16

8.32

3.65

1.000.99

1.661.661.671.671.671.681.681.691.692.352.352.362.362.362.372.372.372.372.382.382.382.382.392.39

4.034.04

5.245.255.255.255.255.265.265.265.275.275.285.285.285.325.325.32

27.42

31.68

53.48

53.66

53.84

54.02

54.20

61.34

92.70

107.06

196.34



S61

28.59

29.44

32.59

61.24

76.84

77.16

77.48

89.71

107.99

200.69



S62

4.03

4.11

2.08

0.83

1.901.00

1.80

1.621.631.631.641.651.651.661.672.362.372.372.382.392.40

4.784.805.295.305.305.315.325.335.34

7.267.427.447.467.547.557.578.058.058.068.07

27.15

31.31

63.86

76.84

77.16

77.48

87.39

106.14

128.42

129.74

130.59

132.96

166.49

198.78



S63

8.33

4.01

1.95

0.80

2.111.00

1.97

1.491.501.511.521.521.531.541.541.581.581.591.591.601.601.611.611.621.621.632.242.252.252.252.262.272.272.282.282.284.774.785.205.215.215.225.237.417.427.427.437.447.457.457.467.537.537.547.557.557.567.578.068.068.068.078.088.088.08

28.45

29.43

32.29

63.89

76.84

77.16

77.48

84.67

106.90

128.40

129.76

132.93

166.48

203.34



S64

8.15

3.91

2.00

3.05

0.88

10.58

1.48

1.992.002.012.01

3.093.11

3.70

4.694.704.704.714.724.724.734.744.74

7.237.237.237.247.247.257.257.257.267.267.277.277.287.297.307.31



S65

28.55

29.46

32.17

39.59

52.48

60.72

76.84

77.16

77.48

84.28

103.85

126.85

127.90

129.11

129.25

142.63

174.75

203.92

6.51

4.01

2.00

2.93

8.05

1.421.431.451.471.481.491.541.851.861.86

3.003.02

3.67

4.624.634.634.644.644.654.664.66

7.167.177.187.187.197.237.247.257.26



S66

26.14

27.37

31.17

39.49

52.70

59.87

76.82

77.14

77.46

83.82

102.34

128.15

128.57

128.64

130.55

133.06

133.95

140.78

173.94

200.79



S67

27.05

30.94

39.20

52.73

59.83

76.83

77.14

77.46

86.50

103.68

128.16

130.54

133.06

173.94

199.62



S68

26.26

27.51

30.00

31.33

40.21

52.41

59.70

71.49

76.83

77.15

77.47

84.87

101.77

108.44

125.81

126.49

128.95

135.11

158.90

175.42

200.50



S69

27.07

29.98

30.95

39.84

52.40

59.65

71.46

76.81

77.13

77.45

87.52

103.06

108.43

125.79

126.45

128.87

135.09

158.86

175.37

199.30

6.32

4.03

2.00

2.80

0.85

8.17



S70



S71

26.92

30.73

41.01

52.94

76.82

77.14

77.46

85.28

103.76

116.68

121.47

123.25

127.22

128.57

128.62

128.82

133.76

133.95

150.82

174.41

199.68



S73


S74

8.25

3.94

2.00

0.94

10.78

1.43

1.951.97

3.053.07

4.674.674.684.694.694.704.714.714.72

7.237.237.247.247.257.257.267.277.277.287.297.297.307.317.327.32

28.51

29.45

32.10

39.39

60.56

76.83

77.15

77.46

84.04

104.02

127.07

127.97

129.23

129.34

142.08

179.28

204.03



S75



S76

4.12

4.11

2.00

1.02

9.65

1.531.531.541.551.562.052.072.082.092.092.10

3.003.01

4.744.754.764.774.78

7.197.207.227.247.247.267.27



S77

6.40

4.00

1.984.05

4.110.88

1.87

3.80

26.26

27.49

29.98

31.27

40.09

59.53

71.54

76.83

77.15

77.47

84.63

101.95

108.53

125.93

126.62

129.08

134.50

159.10

200.66

215.63



S78

3.86

4.00

2.074.00

4.00

0.89

2.09

4.28



S79

6.28

3.99

2.01

1.00

3.894.34

1.241.311.321.54

2.912.93

4.38

7.007.017.047.067.207.227.247.247.24

26.13

27.26

31.02

40.77

50.26

76.84

77.16

77.48

82.53

102.11

116.81

120.72

123.30

127.58

128.89

150.88

178.96

201.18



S80

3.922.042.00

1.95

0.92

3.75

4.18

1401.411.421.431.431.571.581.601.611.621.621.631.821.831.841.861.861.871.87

2.993.00

4.554.564.574.584.594.594.60

7.037.037.057.077.217.227.237.247.247.257.267.27

26.91

30.71

39.55

49.88

76.84

77.16

77.37

77.48

85.17

104.14

116.81

120.69

123.34

127.41

128.95

150.89

178.46

199.75



S81

5.99

4.03

2.00

2.98

0.93

0.91

1.90

6.27

1.401.421.43

1.87

3.023.043.063.073.083.093.103.123.72

4.704.714.724.724.734.734.744.754.756.876.886.886.927.177.197.217.237.247.257.277.287.317.317.317.337.33

26.23

27.41

31.16

31.19

39.47

55.34

60.56

76.83

77.15

77.47

84.30

102.08

112.01

115.89

121.77

127.07

127.93

128.86

129.33

141.93

143.68

159.27

179.28

200.73



ligand- and brønsted acid/base-switchable reaction

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