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Supporting Information
© Wiley-VCH 2008
69451 Weinheim, Germany
Supporting Information
Nickel Catalyzed Reductive Cyclization of Unactivated
1,6-Enynes in the Presence of Organozinc Reagents
Mao Chen, Yue Weng, Mian Guo, Hua Zhang and Aiwen Lei*
College of Chemistry and Molecular Science, Wuhan University, Wuhan, 430072, P. R. China
Experimental Details
General. All reactions were carried out under an atmosphere of nitrogen, unless
otherwise indicated. Flasks were flame-dried and cooled under nitrogen prior to use.
Dichloromethane was distilled from calcium hydride. Tetrahydrofuran (THF) was
dried and distilled from sodium/benzophenone immediately prior to use under
nitrogen atmosphere. CH3CN was dried over anhydrous sodium sulfate (Na2SO4).
Thin layer chromatography (TLC) employed glass 0.25 mm silica gel plates. Flash
chromatography columns were packed with 200-300 mesh silica gel in petroleum
(boiling point is between 60-90oC). Gradient flash chromatography was conducted
eluting with a continuous gradient from petroleum to the indicated solvent, and they
are listed as volume/volume ratios. 1H and 13C NMR data were recorded with a Varian Mercury (300 MHz)
spectrometer with tetramethylsilane as an internal standard. All 1H NMR spectra were
reported in delta (δ) units, parts per million (ppm) downfield from the internal
standard. Coupling constants are reported in Hertz (Hz). High resolution mass spectra
(HRMS) were measured with a Waters Micromass GCT instrument or a Waters
Q-Tof Premier instrument, accurate masses are reported for the molecular ion ([M]+,
[M+1]+, or [M+23]+). E/Z ratios were recorded with a Varian GC 2000 gas
S 1
chromatography instrument with a FID detector. And GC yield were determined by
the same instrument while naphthalene was used as the internal standard.
Synthesis of the substrates for the reductive cyclization
Enynes 1a-1c, 1e, 3a, 3b, 3f and 3g were prepared according to the references.
O
Compound 1a
(3-(allyloxy)but-1-ynyl)benzene (1a).[1] 1H NMR (300MHz, CDCl3): δ 7.45-7.43 (m, 2H),
7.38-7.31 (m, 3H), 6.02-5.92 (m, 1H), 5.34 (d, J = 17.4 Hz, 1H), 5.22 (d, J = 10.2 Hz,
1H), 4.45-4.43 (m, 1H), 4.32 (dd, J = 12.3, 5.1 Hz, 1H), 4.04 (dd, J = 12.5, 6.0 Hz,
1H), 1.54 (d, J = 6.6 Hz, 3H); 13C NMR (75MHz, CDCl3): δ 134.8, 132.0, 129.0,
128.5, 123.0, 117.6, 89.3, 85.3, 69.9, 65.3, 22.4.
Compound 1b
(3-(allyloxy)prop-1-ynyl)benzene (1b).[2] 1H NMR (300MHz, CDCl3): δ 7.34-7.30
(m, 2H), 7.16-7.15 (m, 3H), 5.88-5.71 (m, 1H), 5.21 (dd, J = 17.4, 1.5Hz, 1H), 5.09 (d,
J = 10.2 Hz, 1H), 4.23 (s, 2H), 3.99 (d, J = 5.7 Hz, 2H); 13C NMR (75MHz, CDCl3):
δ 134.1, 131.8, 128.5, 128.4, 122.7, 117.9, 86.4, 85.2, 70.7, 57.9.
Compound 1c
1-(3-(allyloxy)prop-1-ynyl)-4-methoxybenzene (1c).[3]
O
OO
S 2
1H NMR (300MHz, CDCl3): δ 7.31 (d, J = 7.8 Hz, 2H), 6.75 (d, J = 7.5 Hz, 2H),
5.92-5.83 (m, 1H), 5.26 (d, J = 17.4 Hz, 1H), 5.15 (d, J = 10.5 Hz, 1H), 4.29 (s, 2H),
4.05 (d, J = 5.4 Hz, 2H), 3.72 (s, 3H); 13C NMR (75MHz, CDCl3): δ 159.9, 134.4,
133.5, 118.0, 115.0, 114.1, 86.4, 83.8, 70.9, 58.2, 55.5.
Compound 1e
1-(allyloxy)oct-2-yne (1e).[4] 1H NMR (300 MHz, CDCl3): δ 5.96-5.87 (m, 1H), 5.30
(dd, J = 17.1, 1.5 Hz, 1H), 5.20 (d, J = 10.2 Hz, 1H), 4.14 (s, 2H), 4.05 (d, J = 5.7 Hz,
2H), 2.22 (t, J = 7.1 Hz, 2H), 1.54-1.50 (m, 2H), 1.36-1.33 (m, 4H), 0.90 (t, J = 6.9
Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 134.4, 117.7, 87.3, 76.0, 70.6, 57.9, 31.3,
28.5, 22.4, 18.9, 14.1.
TsN
Compound 3a
N-allyl-4-methyl-N-(3-phenylprop-2-ynyl)benzenesulfonamide (3a).[2] 1H NMR (300MHz,
CDCl3): δ 7.78 (d, J = 8.1 Hz, 2H), 7.26-7.24 (m, 5H), 7.06 (d, J = 7.5 Hz, 2H),
5.87-5.74 (m, 1H), 5.33 (d, J = 17.1 Hz, 1H), 5.27 (d, J = 9.9 Hz, 1H), 4.31 (s, 2H),
3.89 (d, J = 6.3 Hz, 2H), 2.34 (s, 3H).
Compound 3b
N-allyl-N-(3-(4-methoxyphenyl)prop-2-ynyl)-4-methylbenzenesulfonamide (3b).[2] 1H NMR
(300MHz, CDCl3): δ 7.42 (d, J = 7.2 Hz, 2H), 6.89 (d, J = 8.1 Hz, 2H), 6.67 (d, J =
8.1 Hz, 2H), 6.42 (d, J = 7.5 Hz, 2H), 5.46-5.40 (m, 1H), 4.98 (d, J = 17.7 Hz, 1H),
4.90 (d, J = 10.2 Hz, 1H), 3.94 (s, 2H), 3.54 (d, J = 6.6 Hz, 2H), 3.42 (s, 3H), 1.99 (s,
OC5H11
TsNO
S 3
3H); 13C NMR (75MHz, CDCl3): δ 159.8, 143.6, 136.2, 133.1, 132.3, 129.7, 127.9,
119.9, 114.4, 113.9, 85.8, 80.3, 55.4, 49.4, 37.0, 21.6.
Compound 3g
(E)-N-(but-2-enyl)-4-methyl-N-(3-phenylprop-2-ynyl)benzenesulfonamide (3g).[5] 1H NMR
(300MHz, CDCl3): δ 7.76 (d, J = 8.1 Hz, 2H), 7.26-7.23 (m, 5H), 7.06 (d, J = 6.6 Hz,
2H), 5.80-5.69 (m, 1H), 5.48-5.39 (m, 1H), 4.29 (s, 2H), 3.81 (d, J = 6.6 Hz, 2H),
2.33 (s, 3H), 1.71 (d, J = 6.3 Hz, 3H); 13C NMR (75MHz, CDCl3): δ 143.7, 136.3,
131.9, 131.8, 129.8, 128.6, 128.4, 128.1, 125.0, 122.6, 85.8, 82.2, 48.9, 36.7, 21.7,
18.1.
Compound 3c
N-allyl-N-(3-(3-methoxyphenyl)prop-2-ynyl)-4-methylbenzenesulfonamide (3c).
To a solution of N-allyl-4-methylbenzenesulfonamide (8.5g, 40mmol),
prop-2-yn-1-ol (3.2mL, 54mmol), and triphenyl-phosphane (14.2g, 54mmol) in
anhydrous THF (130mL) was added diisopropylazodicarboxylate (10.7mL, 54mmol)
at 0oC, and the reaction mixture was gradually warmed to room temperature, and then
stirred overnight. The solvent was removed under vacuum, and the residue was
purified on silica gel to give compound
N-allyl-4-methyl-N-(prop-2-ynyl)benzenesulfonamide (7.6g) in 76% yield.
To a solution of N-allyl-4-methyl-N-(prop-2-ynyl)benzenesulfonamide (1.25g,
5mmol), 1-iodo-3-methoxybenzene (1.28g, 5.5mmol), Pd(PPh3)2Cl2 (70.2mg,
0.1mmol) and CuI (38.1mg, 0.2mmol) in dry CH3CN (5mL) under nitrogent
atmosphere was added NEt3 (1.4mL, 10mmol) at 0oC, and the reaction was warmed to
room temperature, and then stirred overnight. The solvent was removed under
TsN
O
TsN
S 4
vacuum, and the residue was purified on silica gel (ethyl acetate/ petroleum = 1/40 )
to give 3c (1.65g) in 93% yield. 1H NMR (300MHz, CDCl3): δ 7.67 (d, J = 7.8 Hz,
2H), 7.15 (d, J = 7.8 Hz, 2H), 7.04 (t, J = 8.0 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 6.56
(d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 5.74-5.63 (m, 1H), 5.23 (d, J = 17.1 Hz, 1H), 5.16(d,
J = 9.9 Hz, 1H), 4.20 (s, 2H), 3.79(d, J = 6.9 Hz, 2H), 3.67 (s, 3H), 2.23 (s, 3H); 13C
NMR (75MHz, CDCl3): δ 159.4, 143.9, 136.2, 132.3, 129.8, 129.4, 128.0, 124.2,
123.4, 120.2, 117.2, 114.6, 85.9, 81.7, 55.5, 49.5, 36.9, 21.6; HRMS (APCI) calcd for
C20H21NO3S [M]+: 355.1242; found 355.1251.
The remaining N-tethered enynes 3d and 3e were prepared using a procedure
similar to that used to synthesize 3c.
TsN
O
Compound 3d
N-allyl-N-(3-(2-methoxyphenyl)prop-2-ynyl)-4-methylbenzenesulfonamide (3d). 85% yield. 1H NMR (300MHz, CDCl3): δ 7.77 (d, J = 8.1 Hz, 2H), 7.28-7.19 (m, 3H), 6.93 (dd, J
= 7.8, 1.6Hz, 1H), 6.84-6.80 (m, 2H), 5.85-5.76 (m, 1H), 5.34 (d, J = 15.9 Hz, 1H),
5.26 (d, J = 10.2 Hz, 1H), 4.36 (s, 2H), 3.91 (d, J = 6.6 Hz, 2H), 3.80 (s, 3H), 2.90 (s,
3H); 13C NMR (75MHz, CDCl3): δ 159.8, 143.1, 135.7, 133.2, 131.9, 129.6, 129.2,
127.6, 119.9, 119.8, 111.3, 110.2, 85.5, 82.1, 55.4, 48.9, 36.9, 21.2. HRMS (ESI)
calcd for C20H21NO3S [M + Na]+ :378.1140; found 378.1111.
TsNCOOEt
Compound 3e
ethyl 4-(3-(N-allyl-4-methylphenylsulfonamido)prop-1-ynyl)benzoate (3e). 83% yield. 1H NMR (300MHz, CDCl3): δ 7.91 (d, J = 8.1 Hz, 2H), 7.77 (d, J = 7.8 Hz, 2H), 7.25
S 5
(d, J = 7.5 Hz, 2H), 7.11 (d, J = 8.1 Hz, 2H), 5.87-5.74 (m, 1H), 5.35-5.26 (m, 2H),
4.41-4.32 (m, 4H), 3.89 (d, J = 6.3 Hz, 2H), 2.34 (s, 3H), 1.40 (t, J = 7.2 Hz, 3H); 13C
NMR (75MHz, CDCl3): δ 166.1, 143.8, 136.1, 132.2, 131.5, 130.3, 129.8, 129.4,
128.0, 126.9, 120.3, 85.2, 85.0, 61.5, 49.6, 36.9, 21.7, 14.5; HRMS (APCI) calcd for
C22H23NO4S [M]+: 397.1348; found 397.1353.
TsNC5H11
Compound 3f
To a solution of N-allyl-4-methylbenzenesulfonamide (2.11g, 10mmol),
oct-2-yn-1-ol (1.71g, 13.5mmol), and triphenyl-phosphane ( 3.54g, 13.5mmol) in
anhydrous THF (25mL) was added diisopropylazodicarboxylate (2.9mL, 13.5mmol)
at 0oC, and the reaction mixture was gradually warmed to room temperature, and then
stirred overnight. The solvent was removed under vacuum. The residue was dissolved
in ethyl acetate and the resulting solution was washed with brine, dried (Na2SO4),
filtered and concentrated in vacuum. The residue was purified purified on silica gel
(ethyl acetate/ petroleum = 1/40) to afford 3f (1.60g) in 50% yield. 1H NMR
(300MHz, CDCl3): δ 7.66 (d, J = 7.5 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 5.69-5.63 (m,
1H), 5.35-5.13 (m, 2H), 3.99 (s, 2H), 3.73 (d, J = 6.0 Hz, 2H), 2.35 (s, 3H), 1.83-1.80
(m, 2H), 1.19-1.13 (m, 6H), 0.80 (t, J = 6.3 Hz, 3H); 13C NMR (75MHz, CDCl3): δ
143.4, 136.5, 132.5, 129.5, 128.1, 119.8, 86.5, 72.5, 49.1, 36.6, 31.2, 28.3, 22.3, 21.7,
18.6, 14.2. HRMS (ESI) calcd for C18H25NO2S [M + Na]+: 342.1504; found
342.1506.
BocN
Compound 3h
tert-butyl allyl(3-phenylprop-2-ynyl)carbamate (3h).
To a solution of tert-butyl prop-2-ynylcarbamate (2.62g, 16.9mmol), iodobenzene
S 6
(3.57g, 17.5mmol), Pd(PPh3)2Cl2 (141.1mg, 0.2mmol) and CuI (77.3mg ,0.4mmol) in
dry CH3CN (20mL) under nitrogen atmosphere was added NEt3 (3.5g, 35mmol) at
0oC, and the reaction was warmed to room temperature, and then stirred overnight.
The solvent was removed under vacuum, and the residue was purified on silica gel
(ethyl acetate/ petroleum = 1/40) to give tert-butyl 3-phenylprop-2-ynylcarbamate
(3.2g) in 82% yield.
To a solution of tert-butyl 3-phenylprop-2-ynylcarbamate (2.31g, 10mmol) in THF
(50mL) was added sodium hydride (0.6g of a 60% dispersion in mineral oil, 15mmol).
After stirring for 30 min, allyl bromide (1.45g, 12mmol) was added to the above
solution at 0oC, and the reaction was then warmed to room temperature gradually and
stirred for 2 hours. The reaction was quenched by addition of a saturated solution of
NH4Cl (25 mL), and the mixture was extracted with ethyl acetate (3×20 mL). The
combined organic phase was dried over Na2SO4. The solvent was removed under
vacuum, and the residue was purified on silica gel (ethyl acetate/ petroleum = 1/40) to
give 3h (1.47g) in 54% yield. 1H NMR (300MHz, CDCl3): δ 7.43-7.40 (m, 2H),
7.31-7.29 (m, 3H), 5.89-5.76 (m, 1H), 5.24-5.16 (m, 2H), 4.25-4.20 (m, 2H), 4.00 (d,
J = 5.4 Hz, 2H), 1.49 (s, 9H); 13C NMR (75MHz, CDCl3): δ 155.1, 133.6, 131.7,
128.6, 128.3, 123.0, 85.1, 83.4, 80.3, 48.7, 36.3, 28.5; HRMS (APCI) calcd for
C17H21NO2 [M]+: 271.1572; found 271.1562.
CbzN
Compound 3i
benzyl allyl(3-phenylprop-2-ynyl)carbamate (3i).
To a solution of benzyl prop-2-ynylcarbamate (5.68g, 30mmol), iodobenzene
(6.74g, 33mmol), Pd(PPh3)2Cl2 (306.0mg, 0.4mmol) and CuI (155.4mg, 0.8mmol) in
dry CH3CN (50mL) under nitrogent atmosphere was added NEt3 (6.07g, 60mmol) at
0oC, and the reaction was warmed to room temperature, and then stirred overnight.
The solvent was removed under vacuum, and the residue was purified on silica gel
S 7
(ethyl acetate/ petroleum = 1/40) to give benzyl 3-phenylprop-2-ynylcarbamate (5.75g)
in 72% yield.
To a solution of benzyl 3-phenylprop-2-ynylcarbamate (2.65g, 10mmol) in THF
(50mL) was added sodium hydride (0.8g of a 60% dispersion in mineral oil, 20mmol).
After stirring for 30 min, allyl bromide (1.45g, 12mmol) was added to the above
solution at 0oC, and the reaction was then warmed to room temperature gradually and
stirred for 2 hours. The reaction was quenched by addition of a saturated solution of
NH4Cl (20mL), and the mixture was extracted with ethyl acetate (3×20 mL). The
combined organic phase was dried over Na2SO4. The solvent was removed under
vacuum, and the residue was purified on silica gel (ethyl acetate/ petroleum = 1/40) to
give 3i (1.59g) in 52% yield. 1H NMR (300MHz, CDCl3): δ 7.08-7.01 (m, 6H),
7.01-6.97 (m, 4H), 5.53-5.46(m, 1H), 5.00-4.86 (m, 4H), 4.03-3.95 (m, 2H), 3.75 (s,
2H); 13C NMR (75MHz, CDCl3): δ 155.6, 136.5, 132.9, 131.6, 128.4, 128.2, 127.9,
127.7, 122.6, 117.7, 117.3, 84.4, 83.6, 67.4, 48.4, 36.3. HRMS (ESI) calcd for
C20H19NO2 [M + Na]+: 328.1313; found 328.1321.
OCOOEt
Compound 1d
ethyl 4-(3-(allyloxy)prop-1-ynyl)benzoate (1d).
To a solution of sodium hydride (0.4g of a 60% dispersion in mineral oil, 10mmol)
in THF (5mL) at 0 oC, was added portion drop wise ethyl 4-(3-hydroxyprop-1-ynyl)
benzoate (1.0g, 4.9mmol). After stirring for 30 min, allyl bromide (0.8g, 6.6mmol)
was added to the above solution at 0oC, and the reaction was then warmed to room
temperature gradually and stirred for 2 hours. The reaction was quenched by addition
of HCl (2M, 25mL), and the mixture was extracted with dichloromethane (3×20 mL).
The combined organic phase was washed with brine, dried (Na2SO4), filtered and
concentrated in vacuum. The residue was purified on silica gel (ethyl acetate/
petroleum = 1/50) to give 1d (839.1mg) in 70% yield. 1H NMR (300MHz, CDCl3): δ
S 8
7.89 (d, J = 7.8 Hz, 2H), 7.40 (d, J = 8.1 Hz, 2H), 5.92-5.79 (m, 1H), 5.25 (d, J = 17.1
Hz, 1H), 5.15 (d, J = 10.2 Hz, 1H), 4.30-4.24 (m, 4H), 4.04 (d, J = 5.7 Hz, 2H), 1.29
(t, J = 7.1 Hz, 3H); 13C NMR (75MHz, CDCl3): δ 166.1, 134.1, 131.8, 130.3, 129.6,
127.4, 118.2, 88.3, 85.7, 71.1, 61.3, 58.0, 14.5; HRMS (ESI) calcd for C15H16O3 [M +
H]+: 245.1178; found 245.1166.
General Procedures for the Reductive Cyclization
NTs
O
Compound 4b
(Z)-3-(4-methoxybenzylidene)-4-methyl-1-tosylpyrrolidine (4b). (i-Pr)2Zn (6mL,
0.5M in THF) was added to a solution of 3b (355mg, 1.0 mmol) and Ni(acac)2
(25.6mg, 0.1mmol) in anhydrous THF (4mL) at -78oC. The reaction mixture was
stirred at 40oC for 18h under N2, and then quench by adding 2M HCl (25mL). The
mixture was extracted with dichloromethane and the combined organic layers were
washed with saturated NaHCO3 and brine, dried (Na2SO4), and then concentrated in
vacuum. The residue was purified by column chromatography over silica gel (ethyl
acetate/petroleum = 1/20, v/v) to give 4b (318mg, 89%) as a colorless oil. 1H NMR
(300MHz, CDCl3): δ 7.63 (d, J = 8.1 Hz, 2H), 7.20 (d, J = 7.8 Hz, 2H), 6.98 (d, J =
8.4 Hz, 2H), 6.78 (d, J = 8.7 Hz, 2H), 6.06 (s, 1H), 4.12 (d, J = 14.7 Hz, 1H), 3.93 (d,
J = 14.4 Hz, 1H), 3.70 (s, 3H), 3.44 (t, J = 7.8 Hz, 1H), 2.78-2.71 (m, 1H), 2.62 (t, J =
8.4 Hz, 1H), 2.30 (s, 3H), 1.05 (d, J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ
158.7, 143.8, 139.6, 133.0, 129.9, 129.7, 129.5, 127.9, 121.6, 114.1, 55.4, 54.1, 51.0,
39.1, 21.7, 17.1; HRMS (APCI) calcd for C20H23NO3S [M]+: 357.1399; found
357.1404.
All remaining pyrrolidine and tetrahydrofuran derivatives were prepared using a
procedure similar to that used to synthesize 4b.
S 9
NTs
Compound 4a
(Z)-3-benzylidene-4-methyl-1-tosylpyrrolidine (4a).[6] 95% yield, Z/E > 99/1. 1H
NMR (300MHz, CDCl3): δ 7.64 (d, J = 8.1 Hz, 2H), 7.28-7.20 (m, 4H), 7.17-7.12 (m,
1H), 7.05 (d, J = 7.2 Hz, 2H), 6.14 (d, J = 1.8 Hz, 1H), 4.16 (d, J = 14.1 Hz, 1H), 3.96
(d, J = 14.7 Hz, 1H), 3.47 (dd, J = 8.7, 7.5 Hz, 1H), 2.82-2.74 (m, 1H), 2.64 (t, J = 8.4
Hz, 1H), 2.32 (s, 3H), 1.08 (d, J = 6.6 Hz, 3H); 13C NMR (75MHz, CDCl3): δ 143.9,
142.0, 136.8, 133.2, 130.0, 128.8, 128.3, 128.0, 127.2, 122.3, 54.1, 51.1, 39.3, 21.8,
17.2.
NTs
O
Compound 4c
(Z)-3-(3-methoxybenzylidene)-4-methyl-1-tosylpyrrolidine (4c). Colorless oil, 56%
yield, Z/E > 99/1. 1H NMR (300MHz, CDCl3): δ 7.61 (d, J = 8.1 Hz, 2H), 7.21-7.12
(m, 3H), 6.70-6.64 (m, 2H), 6.62-6.57 (m, 1H), 6.09 (d, J = 1.8 Hz, 1H), 4.13 (d, J =
15.0 Hz, 1H), 3.94 (d, J = 15.0 Hz, 1H), 3.69 (s, 3H), 3.44 (t, J = 8.0 Hz, 1H),
2.78-2.71 (m, 1H), 2.63 (t, J = 8.4 Hz, 1H), 2.29 (s, 3H), 1.05 (d, J = 6.9 Hz, 3H); 13C
NMR (75MHz, CDCl3): δ 159.9, 143.9, 142.4, 138.2, 133.1, 130.0, 129.8, 128.0,
122.3, 120.7, 114.2, 112.5, 55.5, 54.1, 51.1, 39.3, 21.8, 17.2; HRMS (APCI) calcd for
C20H23NO3S [M]+: 357.1399; found 357.1387.
NTs
O
S 10
Compound 4d
(Z)-3-(2-methoxybenzylidene)-4-methyl-1-tosylpyrrolidine (4d). Colorless oil, 36%
yield, Z/E > 99/1. 1H NMR (300MHz, CDCl3): δ 7.69 (d, J = 8.1 Hz, 2H), 7.30-7.20
(m, 3H), 7.06-7.04 (m, 1H), 6.97-6.92 (m, 1H), 6.87-6.81 (m, 1H), 6.48 (d, J = 2.1 Hz,
1H), 4.15 (d, J = 14.7 Hz, 1H), 3.99 (d, J = 15.0 Hz, 1H), 3.81 (s, 3H), 3.57-3.52 (m,
1H), 2.91-2.84 (m, 1H), 2.78-2.73 (m, 1H), 2.41 (s, 3H), 1.17 (d, J = 6.6 Hz, 3H); 13C
NMR (75MHz, CDCl3): δ 156.9, 143.9, 142.1, 133.5, 130.0, 128.9, 128.8, 128.1,
125.9, 120.8, 117.1, 110.9, 55.8, 54.3, 51.0, 39.4, 21.9, 17.3. HRMS (ESI) calcd for
C20H23NO3S [M + Na]+: 380.1296; found: 380.1290.
NTs
C5H11
Compound 4f
(Z)-3-hexylidene-4-methyl-1-tosylpyrrolidine (4f). Colorless oil 62%, Z/E > 99/1. 1H
NMR (300MHz, CDCl3): δ 7.63 (d, J = 7.8 Hz, 2H), 7.25 (d, J = 7.8 Hz, 2H), 5.07 (s,
1H), 3.79 (d, J = 14.1 Hz, 1H), 3.63 (d, J = 13.8 Hz, 1H), 3.47-3.39 (m, 1H), 2.56 (d,
J = 3.9 Hz, 2H), 2.34 (s, 3H), 1.80-1.77 (m, 2H), 1.23-1.15 (m, 6H), 0.93 (d, J = 5.7
Hz, 3H), 0.78 (t, J = 6.3 Hz, 3H); 13C NMR (75MHz, CDCl3): δ 143.7, 139.7, 133.0,
129.8, 128.0, 122.2, 55.2, 49.9, 37.4, 31.6, 29.4, 29.1, 22.7, 21.7, 16.9, 14.2. HRMS
(ESI) calcd for C18H27NO2S [M+H]+: 322.1841; found: 322.1828.
NTs
COOEt
Compound 4e
(Z)-ethyl 4-((4-methyl-1-tosylpyrrolidin-3-ylidene)methyl)benzoate (4e). Colorless
oil, 65% yield, Z/E = 74/26. 1H NMR (300MHz, CDCl3): δ 8.03-8.00 (m, 2H),
7.75-7.70 (m, 2H), 7.36-7.26 (m, 2H), 7.25-7.18 (m, 2H), 6.26 (s, 1H), 4.38 (q, J =
6.9 Hz, 2H), 4.27-4.15 (m, 1H), 4.03 (d, J = 15.0 Hz, 0.7H), 3.80 (d, J = 15.9 Hz,
S 11
0.3H), 3.57 (t, J = 8.1 Hz, 0.7H), 3.28-3.20 (m, 0.9H), 2.94-2.89 (m, 0.7H), 2.74 (t, J
= 8.7 Hz, 0.7H), 2.43-2.41 (m, 3H), 1.40 (t, J = 7.2 Hz, 3H), 1.18 (d, J = 6.6 Hz,
2.1H), 1.12 (d, J = 6.6 Hz, 0.9H); 13C NMR (75MHz, CDCl3): δ 166.5, 144.9, 144.0,
141.1, 133.0, 130.0, 129.0, 128.1, 128.0, 122.0, 121.7, 61.2, 55.9, 54.0, 53.4, 51.1,
39.6, 35.5, 21.8, 18.6, 17.1, 14.6; HRMS (APCI) calcd for C22H25NO4S [M]+:
399.1504; found 399.1501.
NTs
Compound 4g
(Z)-3-benzylidene-4-ethyl-1-tosylpyrrolidine (4g). 66% yield, Z/E > 99/1, and
(E)-N-(but-2-enyl)-4-methylbenzenesulfonamide was obtained as a by product in 24%
yield. 4g: 1H NMR (300MHz, CDCl3): δ 7.64 (d, J = 8.1 Hz, 2H), 7.29-7.23 (m, 4H),
7.22-7.15 (m, 1H), 7.05 (d, J = 7.5 Hz, 2H), 6.17 (s, 1H), 4.04 (m, 2H), 3.35 (dd, J =
9.0, 7.3 Hz, 1H), 2.89 (dd, J = 9.3, 6.0 Hz, 1H), 2.62-2.58 (m, 1H), 2.33 (s, 3H),
1.63-1.55 (m, 1H), 1.36-1.26 (m, 1H), 0.86 (t, J = 7.5 Hz, 3H); 13C NMR (75MHz,
CDCl3): δ 143.9, 140.7, 136.8, 133.1, 130.0, 128.8, 128.3, 128.0, 127.2, 123.1, 52.1,
51.0, 46.5, 26.2, 21.8, 12.1. HRMS (ESI) calcd for C20H23NO2S [M+H]+: 342.1528;
found: 342.1503. (E)-N-(but-2-enyl)-4-methylbenzenesulfonamide: 1H NMR
(300MHz, CDCl3): δ 7.75 (d, J = 8.1 Hz, 2H), 7.31 (d, J = 8.1 Hz, 2H), 5.63-5.52 (m,
1H), 5.38-5.28 (m, 1H), 4.44 (broad, 1H), 3.50 (t, J = 6.0 Hz, 2H), 2.43 (s, 3H), 1.61
(d, J = 6.3 Hz, 3H);
NBoc
Compound 4h
(Z)-tert-butyl 3-benzylidene-4-methylpyrrolidine-1-carboxylate (4h). 1H NMR
S 12
(300MHz, CDCl3): δ 7.07-7.01 (m, 2H), 6.97-6.95 (m, 3H), 6.05 (s, 1H), 4.06-3.99(m,
2H), 3.47-3.43 (m, 1H), 2.70-2.61 (m, 2H), 1.23 (s, 9H), 0.99 (d, J = 6.3 Hz, 3H); 13C
NMR (75MHz, CDCl3): δ 154.7, 144.1, 143.1, 137.2, 128.5, 128.3, 126.8, 121.3, 79.6,
52.1, 51.6, 49.2, 39.2, 38.5, 28.6, 17.0; HRMS (APCI) calcd for C17H23NO2 [M]+:
273.1729; found 273.1735.
NCbz
Compound 4i (Z)-benzyl 3-benzylidene-4-methylpyrrolidine-1-carboxylate (4i). Colorless oil,
66% yield, Z/E > 99/1. 1H NMR (300MHz, DMSO-D6): δ 7.34-7.30 (m, 7H),
7.23-7.20 (m, 3H), 6.35 (s, 1H), 5.07 (s, 2H), 4.33-4.12 (m, 2H), 3.69-3.65 (m, 1H),
2.93-2.90 (m, 2H), 1.16 (d, J = 5.7 Hz, 3H); 13C NMR (75MHz, CDCl3): δ 154.9,
143.3, 142.4, 137.0, 128.6, 128.3, 128.0, 126.9, 121.6, 66.9, 52.1, 51.9, 49.5, 48.9,
39.2, 38.4, 16.9; HRMS (ESI) calcd for C20H21NO2 [M + Na]+: 330.1470; found
330.1473.
O
Coumpound 2a
(Z)-3-benzylidene-2,4-dimethyltetrahydrofuran (2a).[7] Colorless oil, 72% yield,
Z/E > 99/1. 1H NMR (300MHz, CDCl3): δ 7.25-7.23 (m, 2H), 7.18-7.15 (m, 3H), 6.23
(s, 0.4H), 6.14 (s, 0.6H), 5.10-5.02 (m, 1H), 4.05 (t, J = 7.8 Hz, 0.6H), 3.92(t, J = 7.7
Hz, 0.4H), 3.47 (t, J = 7.5 Hz, 0.4Hz), 3.25 (t, J = 8.7 Hz, 0.6H), 2.86-2.79 (m, 1H),
1.17 (d, J = 6.6 Hz, 3H), 1.11 (d, J = 6.9 Hz, 3H); 13C NMR (75MHz, CDCl3): δ 151.8,
151.1, 137.4, 128.7, 126.8, 120.5, 120.0, 76.1, 73.3, 72.3, 41.2, 39.3, 19.8, 19.0, 18.6,
15.5.
S 13
O
Compound 2b
(Z)-3-benzylidene-4-methyltetrahydrofuran (2b).[6] Colorless oil 66% (GC yield
84%), Z/E > 99/1. 1H NMR (300MHz, CDCl3): δ 7.28-7.23 (m, 2H), 7.16-7.14 (m,
1H), 7.12-7.04 (m, 2H), 6.21 (d, J = 2.1 Hz, 1H), 4.64-4.51 (m, 2H), 3.99 (t, J = 7.7
Hz, 1H), 3.30 (t, J = 8.0 Hz, 1H), 2.86-2.79 (m, 1H), 1.14 (d, J = 6.6 Hz, 3H); 13C
NMR (75MHz, CDCl3): δ 146.8, 137.7, 128.7, 128.1, 126.7, 120.2, 74.6, 70.5, 40.1,
16.7.
O
O
Compound 2c
(Z)-3-(4-methoxybenzylidene)-4-methyltetrahydrofuran (2c). Colorless oil, 65%
yield (GC yield 77%), Z/E > 99/1. 1H NMR (300MHz, CDCl3): δ 6.98 (d, J = 8.4 Hz,
2H), 6.78 (d, J = 8.4 Hz, 2H), 6.14 (s, 1H), 4.61-4.47 (m, 2H), 3.97 (t, J = 7.7 Hz, 1H),
3.70 (s, 3H), 3.27 (t, J = 8.0 Hz, 1H), 2.82-2.75 (m, 1H), 1.11 (d, J = 6.6 Hz, 3H); 13C
NMR (75MHz, CDCl3): δ 158.4, 144.2, 130.5, 129.3, 119.5, 114.2, 74.5, 70.4, 55.4,
39.9, 16.7; HRMS (APCI) calcd for C13H16O2 [M]+: 204.1150; found 204.1148.
O
COOEt
Compound 2d
(Z)-ethyl-4-((4-methyldihydrofuran-3(2H)-ylidene)methyl)benzoate (2d).
Colorless oil, 39% yield, Z/E = 75/25. 1H NMR (300MHz, CDCl3): δ 7.93 (d, J = 7.2
Hz, 2H), 7.10 (d, J = 7.2 Hz, 2H), 6.25 (s, 1H), 4.65-4.47 (m, 2H), 4.30-4.27 (m, 2H),
4.00 (t, J = 6.9 Hz, 1H), 3.31 (t, J = 7.4 Hz, 1H), 2.85-2.83 (m, 1H), 1.30 (t, J = 5.9
Hz, 3H), 1.14 (d, J = 5.4 Hz, 3H); 13C NMR (75MHz, CDCl3): δ 166.6, 149.8, 142.0,
S 14
130.0, 128.1, 127.9, 119.6, 74.4, 70.5, 61.1, 40.3, 16.6, 14.6; HRMS (APCI) calcd for
C15H18O3 [M]+: 246.1258; found 246.1256.
O
C5H11
Compound 2e
(Z)-3-hexylidene-4-methyltetrahydrofuran (2e). Colorless oil, 65% yield, E/Z >
99/1. 1H NMR (300MHz, CDCl3): δ 5.16-5.08 (m, 1H), 4.26 (s, 2H), 3.95 (t, J = 7.7
Hz, 1H), 3.23 (t, J = 8.1 Hz, 1H), 2.60-2.57 (m, 1H), 1.85-1.81 (m, 2H), 1.29-1.20 (m,
6H), 1.00 (d, J = 6.6 Hz, 3H), 0.82 (t, J = 6.8 Hz, 3H); 13C NMR (75MHz, CDCl3): δ
143.6, 119.4, 75.5, 69.4, 38.0, 31.5, 28.5, 28.3, 22.6, 16.3, 14.1; HRMS (APCI) calcd
for C11H20O [M]+: 168.1514; found 168.1521.
[1] F. A. Hicks, N. M. Kablaoui, S. L. Buchwald, J. Am. Chem. Soc. 1999, 121, 5881-5898. [2] Y. Tang, L. Deng, Y. Zhang, G. Dong, J. Chen, Z. Yang, Org. Lett. 2005, 7, 1657-1659. [3] T. Shibata, N. Toshida, K. Takagi, J. Org. Chem. 2002, 67, 7446-7450. [4] K. M. Miller, T. F. Jamison, J. Am. Chem. Soc. 2004, 126, 15342-15343. [5] S. I. Lee, S. M. Kim, S. Y. Kim, Y. K. Chung, Synlett 2006, 2256-2260. [6] H.-Y. Jang, M. J. Krische, J. Am. Chem. Soc. 2004, 126, 7875-7880. [7] K. Miura, M. Funatsu, H. Saito, H. Ito, A. Hosomi, Tetrahedron Lett. 1996, 37, 9059-9062.
S 15
TsN
ppm (f1)0.01.02.03.04.05.06.07.08.0
7.79
17.
764
7.26
37.
242
7.07
27.
049
5.84
95.
815
5.79
35.
759
5.36
05.
302
5.28
85.
254
4.30
73.
899
3.87
8
2.33
8
1.56
6
-0.0
00
1.76
5.551.66
0.94
1.091.07
2.14
2.21
3.00
3a
S 16
TsNO
3b
S 17
ppm (t1)050100150
159.
833
143.
623
136.
195
133.
099
132.
296
129.
678
127.
937
119.
927
114.
388
113.
929
85.8
3180
.320
77.8
2577
.401
76.9
73
55.4
26
49.3
89
36.9
78
21.5
79
TsNO
3b
S 18
TsN
O
ppm (t1)0.01.02.03.04.05.06.07.08.0
7.68
47.
658
7.16
67.
140
7.07
17.
044
7.01
86.
743
6.71
66.
573
6.54
76.
502
5.73
75.
724
5.70
45.
682
5.67
05.
661
5.64
85.
627
5.25
65.
199
5.17
45.
141
4.19
93.
799
3.77
83.
657
2.23
4
0.00
0
1.74
1.830.89
0.81
0.82
2.08
2.132.94
3.00
0.951.00
0.700.84
3c
S 19
ppm (t1)050100150
159.
394
143.
853
136.
147
132.
276
129.
794
129.
442
128.
017
124.
182
123.
402
120.
154
117.
230
114.
568
85.8
5981
.702
77.8
2677
.402
76.9
77
55.4
61
49.5
24
36.9
43
21.6
27
TsN
O
3c
S 20
ppm (t1)0.01.02.03.04.05.06.07.08.0
7.78
67.
759
7.27
87.
273
7.26
17.
250
7.21
97.
191
6.94
56.
940
6.92
06.
914
6.83
96.
824
6.81
66.
796
5.85
05.
816
5.79
35.
760
5.39
65.
343
5.27
65.
242
4.35
53.
919
3.89
73.
800
2.29
0
0.00
0
1.81
2.870.911.70
0.89
1.050.94
2.12
2.222.93
3.00
TsN
O
3d
S 21
ppm (t1)050100150
159.
777
143.
143
135.
737
133.
152
131.
859
129.
603
129.
203
127.
620
119.
920
119.
832
111.
276
110.
237
85.4
7882
.091
77.2
6176
.837
76.4
13
55.3
64
48.8
93
36.8
75
21.1
92
TsN
O
3d
S 22
ppm (f1)0.01.02.03.04.05.06.07.08.0
7.92
87.
901
7.78
67.
760
7.26
77.
242
7.12
37.
096
5.86
85.
846
5.83
55.
826
5.81
25.
790
5.77
95.
769
5.75
75.
735
5.35
35.
293
5.25
9
4.41
14.
388
4.36
44.
340
4.32
2
3.90
13.
880
2.34
11.
419
1.39
51.
371
0.00
0000
0
1.821.69
1.961.75
0.82
2.16
3.00
4.12
2.84
1.98
TsNCOOEt
3e
S 23
ppm (f1)050100150
166.
091
143.
825
136.
110
132.
176
131.
547
130.
276
129.
759
129.
437
128.
042
126.
909
120.
269
85.1
6084
.980
77.6
7377
.249
76.8
25
61.4
53
49.6
26
36.8
83
21.7
00
14.5
31
TsNCOOEt
3e
S 24
ppm (f1)0.01.02.03.04.05.06.07.08.0
7.77
87.
751
7.26
17.
233
7.06
67.
044
5.80
25.
781
5.75
95.
730
5.70
85.
688
5.48
15.
460
5.43
35.
409
5.38
54.
288
3.82
53.
803
2.32
8
1.72
21.
701
1.57
5
0.00
0000
1.81
5.001.66
1.02
0.95
2.16
2.10
3.00
3.06TsN
3g
S 25
ppm (t1)050100150
143.
677
136.
340
131.
910
131.
762
129.
762
128.
625
128.
399
128.
117
124.
968
122.
584
85.8
4782
.155
77.7
6977
.344
76.9
21
48.8
70
36.7
12
21.7
1018
.083
TsN
3g
S 26
ppm (f1) 0.05.0
7.67
77.
651
7.22
57.
198
5.72
15.
709
5.68
65.
664
5.63
15.
609
5.22
65.
166
5.13
13.
990
3.74
23.
722
2.34
7
1.82
7
1.18
31.
162
1.14
20.
817
0.79
80.
775
-0.0
00
1.71
1.86
0.78
1.88
2.062.14
3.00
1.92
6.90
3.21TsN
C5H11
3f
S 27
ppm (f1)50100150
143.
399
136.
472
132.
450
129.
522
128.
058
119.
762
86.5
25
77.6
7677
.253
76.8
2972
.542
49.1
20
36.5
88
31.1
8728
.278
22.3
3621
.736
18.6
2914
.187
TsNC5H11
3f
S 28
ppm (f1)0.01.02.03.04.05.06.07.08.0
7.43
17.
423
7.41
17.
399
7.31
07.
301
7.28
95.
893
5.87
45.
855
5.84
05.
817
5.79
85.
783
5.76
35.
242
5.19
45.
164
4.24
94.
008
3.99
0
1.48
8
1.952.96
0.91
1.90
1.872.00
9.33
NBoc
3h
S 29
ppm (f1)050100150
155.
052
133.
566
131.
731
128.
649
128.
331
123.
028
85.1
35
83.3
7080
.310
77.6
5777
.232
76.8
06
48.7
06
36.3
45
28.4
50
NBoc
3h
S 30
ppm (t1) 0.01.02.03.04.05.06.07.08.0
7.07
27.
040
7.01
46.
970
5.52
15.
501
5.46
84.
868
4.03
23.
956
3.75
2
5.45
0.72
4.00
2.132.18
3.40
NCbz
3i
S 31
ppm (t1) 050100150
155.
551
136.
474
132.
917
131.
604
128.
373
128.
174
127.
894
127.
704
122.
636
117.
706
117.
294
84.4
3383
.623
77.4
5977
.035
76.6
1067
.363
48.3
54
36.3
44
NCbz
3i
S 32
ppm (t1)0.01.02.03.04.05.06.07.08.0
7.33
57.
328
7.31
67.
304
7.16
17.
152
5.87
65.
857
5.84
15.
822
5.80
05.
783
5.76
55.
746
5.70
8
5.23
75.
232
5.17
95.
174
5.11
05.
076
4.23
2
4.00
23.
983
0.00
000
2.992.06
0.77
2.342.00
0.860.88
O
1b
S 33
ppm (f1)050100150
134.
139
131.
805
128.
504
128.
368
122.
740
117.
869
86.4
1085
.198
77.7
6977
.344
76.9
21
70.6
99
57.9
40
O
1b
S 34
OO
ppm (t1)0.01.02.03.04.05.06.07.08.0
7.32
07.
294
6.76
46.
739
5.91
95.
900
5.88
15.
862
5.84
25.
827
5.28
95.
231
5.16
95.
134
4.28
54.
058
4.04
03.
716
-0.0
00
1.85
1.90
0.79
0.880.85
2.051.83
3.00
1c
S 35
ppm (f1)050100150
159.
927
134.
370
133.
465
118.
019
114.
957
114.
123
86.4
0983
.837
77.7
1377
.290
76.8
67
70.8
55
58.2
3555
.474
OO
1c
S 36
ppm (t1)0.01.02.03.04.05.06.07.08.0
7.90
47.
878
7.41
77.
390
5.91
95.
899
5.88
25.
864
5.84
35.
824
5.80
85.
789
5.28
15.
224
5.16
55.
131
4.29
54.
260
4.23
64.
050
4.03
1
1.31
11.
288
1.26
4
0.00
0
0.76
3.36
0.86
2.004.65
0.87
1.98
2.02
OCOOEt
1d
S 37
ppm (f1) 050100150
166.
081
134.
104
131.
754
130.
245
129.
564
127.
355
118.
110
88.2
6285
.670
77.7
3877
.314
76.8
8970
.996
61.2
8557
.979
14.4
50
OCOOEt
1d
S 38
ppm (t1)0.01.02.03.04.05.06.0
5.96
45.
946
5.92
95.
907
5.88
85.
872
5.33
35.
328
5.27
65.
271
5.22
05.
186
4.13
64.
060
4.04
1
2.24
02.
216
2.19
3
1.54
31.
520
1.49
71.
360
1.34
71.
337
1.32
80.
922
0.89
90.
876
-0.0
00
0.90
2.00
0.83
0.93
2.04
2.10
2.214.78
3.24O
C5H11
1e
S 39
ppm (f1)050100150
134.
451
117.
685
87.2
53
77.6
6777
.244
76.8
1975
.967
70.5
5457
.907
31.2
4028
.512
22.3
7018
.910
14.1
10
OC5H11
1e
S 40
ppm (t1)0.01.02.03.04.05.06.07.08.0
7.45
47.
440
7.42
97.
316
6.01
55.
997
5.97
95.
958
5.94
05.
923
5.37
05.
312
5.23
45.
200
4.45
14.
429
4.35
34.
336
4.31
24.
295
4.07
44.
054
4.03
34.
012
1.55
41.
532
-0.0
00
1.92
0.92
2.69
0.86
0.930.89
0.981.00
3.38O
1a
S 41
O
1a
S 42
ppm (t1)0.01.02.03.04.05.06.07.08.0
7.64
97.
622
7.28
27.
258
7.23
37.
206
7.16
87.
144
7.06
57.
041
6.13
96.
133
4.18
24.
135
3.98
73.
938
3.49
53.
470
3.46
63.
441
2.81
52.
793
2.77
02.
748
2.67
22.
643
2.61
6
2.31
91.
089
1.06
7
-0.0
0000
0
1.59
3.380.871.63
0.981.01
0.88
0.80
0.99
1.00
2.99
3.06
NTs
4a
S 43
NTs
ppm (t1)050100150
143.
908
142.
046
136.
815
133.
177
130.
001
128.
815
128.
325
127.
992
127.
237
122.
344
77.7
5777
.334
76.9
09
54.1
0751
.055
39.3
29
21.7
6517
.177
4a
S 44
ppm (f1)0.01.02.03.04.05.06.07.08.0
7.64
07.
613
7.21
77.
191
6.99
56.
967
6.79
46.
765
6.05
7
4.14
54.
096
3.95
53.
907
3.70
43.
469
3.44
33.
417
2.77
82.
755
2.73
32.
711
2.64
72.
618
2.59
1
2.30
01.
058
1.03
6
0.00
0000
1.84
1.991.931.85
0.98
1.071.192.791.05
1.070.99
3.00
3.02
NTs
O
4b
S 45
NTs
O
ppm (t1)050100150
158.
668
143.
788
139.
563
133.
038
129.
896
129.
681
129.
480
127.
872
121.
624
114.
129
77.7
6077
.334
76.9
08
55.4
2654
.082
50.9
66
39.1
34
21.6
6717
.106
4b
S 46
ppm (t1)0.01.02.03.04.05.06.07.08.0
7.62
67.
599
7.21
07.
181
7.15
37.
126
6.69
96.
692
6.66
56.
644
6.61
96.
570
6.09
36.
087
4.15
04.
100
3.96
73.
917
3.69
43.
474
3.44
53.
421
2.78
42.
760
2.73
72.
715
2.65
62.
627
2.60
0
2.29
31.
064
1.04
1
-0.0
0000
0
0.85
1.02
1.00
0.920.96
3.00
2.95
0.83
1.75
0.94
3.00
2.71
1.68
NTs
O
4c
S 47
NTs
O
ppm (t1)050100150
159.
885
143.
912
142.
401
138.
188
133.
093
129.
992
129.
769
127.
958
122.
266
120.
695
114.
249
112.
542
77.8
2877
.403
76.9
79
55.4
5054
.113
51.0
53
39.2
92
21.7
5117
.168
4c
S 48
ppm (t1)0.01.02.03.04.05.06.07.08.0
7.70
77.
680
7.30
77.
280
7.26
17.
231
7.20
37.
064
7.04
3
6.96
86.
944
6.92
06.
871
6.84
3
6.48
26.
475
4.17
84.
129
4.01
23.
962
3.80
63.
573
3.54
43.
520
2.90
82.
903
2.88
62.
862
2.84
0
2.78
32.
754
2.72
72.
412
1.58
1
1.18
51.
163
-0.0
0000
0
4.350.910.981.04
0.912.76
1.09
1.01
3.06
3.00
0.89
0.91
0.84
1.73
NTs
O
4d
S 49
NTs
O
ppm (t1)50100150
156.
917
143.
889
142.
059
133.
470
130.
041
128.
930
128.
811
128.
072
125.
869
120.
814
117.
098
110.
873
77.8
2677
.402
76.9
78
55.7
6754
.332
50.9
83
39.3
64
21.8
5117
.337
4d
S 50
ppm (t1)0.01.02.03.04.05.06.07.08.0
0.7
2.9
0.30.71.0
0.70.7
1.8
0.9
1.5
1.8
2.4
1.9
2.62.10.9
0.9
NTs
COOEt
Z/E = 7/3
4e
S 51
NTs
COOEt
ppm (t1)050100150
166.
468
144.
817
143.
988
141.
084
132.
967
130.
005
128.
982
128.
101
127.
960
121.
967
121.
660
77.7
0277
.278
76.8
53
61.2
1555
.942
53.9
7553
.431
51.0
9239
.554
35.5
30
21.7
5518
.620
17.0
5814
.560
4e
S 52
NTs
ppm (f1)0.01.02.03.04.05.06.07.08.0
7.65
27.
625
7.28
57.
260
7.23
77.
212
7.17
37.
147
7.05
97.
034
6.17
0
4.09
1
4.03
9
3.98
3
3.38
33.
358
3.35
23.
328
2.90
32.
883
2.87
22.
852
2.62
22.
601
2.58
0
2.32
61.
643
1.62
31.
597
1.58
61.
578
1.55
3
1.36
11.
336
1.31
01.
289
1.26
3
0.88
30.
858
0.83
30.
0000
00
1.80
3.601.111.81
0.91
2.06
1.15
1.03
0.99
3.00
1.42
1.18
3.07
4g
S 53
NTs
ppm (f1)050100150
143.
881
140.
740
136.
818
133.
107
129.
972
128.
784
128.
320
127.
956
127.
206
123.
082
77.7
6877
.344
76.9
19
52.0
9550
.980
46.5
40
26.2
3821
.762
12.0
59
4g
S 54
ppm (f1)0.01.02.03.04.05.06.07.08.0
7.76
17.
734
7.32
57.
298
7.26
6
5.60
75.
585
5.55
75.
535
5.37
25.
351
5.32
95.
301
4.44
0
3.52
43.
504
3.48
3
2.43
3
1.61
71.
597
0.00
0000
1.66
0.85
0.83
0.82
1.80
3.00
1.87
2.93
TsHN
4j
S 55
ppm (t1)0.01.02.03.04.05.06.07.08.0
7.64
57.
619
7.26
17.
235
5.07
1
3.81
03.
763
3.65
43.
608
3.47
13.
432
3.39
12.
565
2.55
22.
343
1.79
51.
771
1.22
11.
199
1.17
81.
157
0.93
70.
918
0.80
20.
781
0.75
8
1.77
1.75
0.83
0.970.980.99
1.843.00
2.16
6.553.193.15
NTs
C5H11
4f
S 56
ppm (t1)050100150
143.
726
139.
699
133.
026
129.
843
127.
992
122.
193
77.7
5477
.331
76.9
07
55.2
4949
.888
37.3
82
31.5
7829
.387
29.0
9522
.697
21.7
0916
.891
14.2
11
NTs
C5H11
4f
S 57
ppm (f1) 0.01.02.03.04.05.06.07.08.0
7.07
27.
011
6.97
36.
949
6.05
0
4.05
73.
992
3.47
03.
426
2.68
3
1.23
31.
001
0.98
01.873.02
0.85
2.00
0.98
1.81
10.43.83
NBoc
4h
S 58
ppm (f1) 050100150
154.
686
143.
066
144.
082
137.
196
128.
532
128.
326
126.
814
121.
250
79.5
6677
.604
77.1
8176
.757
52.1
1751
.587
49.1
6039
.217
38.5
31
28.6
46
16.9
88
NBoc
4h
S 59
ppm (t1) 0.01.02.03.04.05.06.07.08.0
7.34
37.
330
7.22
77.
205
6.34
5
5.06
5
4.32
94.
280
4.23
04.
175
4.12
33.
685
3.64
83.
337
2.92
32.
905
1.16
51.
146
6.62.7
0.9
2.0
1.6
0.8
1.8
3.3
NCbz
4i
S 60
ppm (t1) 50100150
154.
933
143.
286
142.
383
136.
957
128.
562
128.
328
128.
053
126.
914
121.
605
77.6
3377
.211
76.7
8766
.908
52.0
8851
.859
49.5
1348
.876
39.1
5138
.419
16.9
28
NCbz
4i
S 61
ppm (t1)0.01.02.03.04.05.06.07.08.0
7.25
27.
228
7.18
27.
154
6.22
66.
144
5.09
95.
077
5.04
25.
021
4.08
04.
054
4.02
83.
950
3.92
43.
899
3.49
23.
468
3.44
23.
275
3.24
63.
217
2.85
62.
833
2.81
12.
790
1.18
01.
158
1.11
81.
095
0.00
0
0.47
2.133.08
0.56
1.00
0.640.46
0.480.66
0.99
3.483.13
O
2a
S 62
O
ppm (t1)050100150
151.
793
151.
113
137.
419
128.
666
126.
782
120.
531
120.
027
77.7
7577
.351
76.9
2776
.070
73.3
4672
.263
41.1
88
39.2
96
19.7
6018
.952
18.5
6215
.535
2a
S 63
ppm (f1)0.01.02.03.04.05.06.07.08.0
7.28
07.
255
7.23
07.
159
7.14
47.
120
7.09
57.
069
7.04
46.
214
6.20
7
4.64
24.
595
4.55
64.
509
4.01
53.
989
3.96
43.
327
3.30
03.
274
2.85
62.
833
2.81
02.
788
1.14
61.
124
-0.0
0000
0
2.391.282.30
1.06
2.61
1.19
1.11
1.00
4.51
O
2b
S 64
O
2b
S 65
ppm (f1)0.01.02.03.04.05.06.07.08.0
6.99
46.
966
6.79
76.
769
6.13
7
4.60
64.
559
4.52
04.
474
3.99
13.
966
3.94
03.
699
3.30
03.
273
3.24
72.
819
2.79
72.
775
2.75
3
1.11
71.
095
0.00
0000
2.102.07
1.00
2.18
1.073.27
1.01
1.01
3.14
O
O
2c
S 66
O
O
ppm (f1)050100150
158.
431
144.
246
130.
489
129.
333
119.
543
114.
159
77.7
8177
.357
76.9
3374
.548
70.4
42
55.4
47
39.9
17
16.6
82
2c
S 67
ppm (t1)0.05.0
7.93
97.
915
7.11
17.
087
6.24
6
4.64
54.
597
4.55
64.
513
4.47
74.
294
4.27
34.
023
4.00
03.
977
3.33
83.
314
3.28
92.
848
2.83
01.
323
1.30
31.
284
1.15
11.
133
-0.0
0000
0
0.80
0.73
3.24
1.90
0.70
3.59
0.83
1.71
1.84
2.24
O
COOEt
2d
S 68
ppm (f1)050100150
166.
563
149.
790
141.
983
129.
981
128.
061
127.
893
119.
562
77.7
4377
.319
76.8
9474
.446
70.5
3061
.106
40.3
25
16.5
86
14.5
51
O
COOEt
2d
S 69
ppm (t1)0.01.02.03.04.05.0
5.15
05.
143
5.13
45.
126
5.11
85.
110
5.10
25.
094
4.25
73.
971
3.94
53.
920
3.25
83.
231
3.20
4
2.59
22.
570
1.84
31.
819
1.29
31.
269
1.24
71.
219
1.21
01.
007
0.98
5
0.83
70.
816
0.79
2
-0.0
0000
00.80
1.74
0.84
0.84
1.92
3.00
6.72
3.57
0.72
O
C5H11
2e
S 70
O
C5H11
2e
S 71
ppm (t1)0.01.02.03.04.05.06.07.08.0
7.64
17.
613
7.26
97.
245
7.21
97.
191
7.15
47.
129
7.05
57.
030
6.12
3
4.17
54.
126
3.98
23.
933
3.48
53.
456
3.43
2
2.78
02.
757
2.73
52.
666
2.63
72.
610
2.30
31.
077
1.05
5
-0.0
00
1.63
3.401.061.73
0.38
1.001.05
0.83
3.05
2.87
1.00
1.00
NTs
Ph
DNTs
Ph
D
+NTs
Ph+
S 72
NPh
Ts1) 10% Ni(acac)2 (10%)
3.0eq. (iPr)2Zn
2) CD3COODNTs
Ph
DNTs
Ph
D
+NTs
Ph+
5 6 4a
5% = [1*(0.80-0.38)/0.8]*100% = 53%
6% = [3*(3.06-2.87)/3.06]*100% = 19%
4a% = (100% - 5% - 6%) = 28%
S 73
NTs
Ph
DNTs
Ph
D
+NTs
Ph+
ppm (t1)0.01.02.03.04.05.06.07.08.0
7.73
47.
707
7.37
47.
350
7.32
47.
297
7.26
37.
236
7.15
37.
128
6.22
46.
218
4.27
4
4.22
4
4.06
7
4.01
7
3.58
23.
553
3.52
8
2.88
62.
863
2.84
0
2.75
12.
722
2.69
5
2.41
4
1.17
91.
157
1.67
4.011.601.79
0.45
0.981.03
0.89
3.50
2.78
0.93
1.00
repeat
S 74
NPh
Ts1) 10% Ni(acac)2 (10%)
3.0eq. ( iPr)2Zn
2) CD3COODNTs
Ph
DNTs
Ph
D
+NTs
Ph+
repeat
5 6 4a
5% = [1*(0.80-0.45)/0.8]*100% = 44%
6% = [3*(3.06-2.78)/3.06]*100% = 27%
4a% = (100% - 5% - 6%) = 29%
S 75
NOE experiment
NTs
HHO
H
H
H
H
NOENOE
NOE
S 76