Y. G énisson et al.
FULL PAPER
column chromatography on silica gel (petroleum ether/EtOAc, 99:1
to 95:5) to give 32 (203.6 mg, 85%) as a colorless oil. Rf = 0.38
(petroleum ether/EtOAc, 95:5). [α]2D5 = +56 (c = 1.9, CHCl3). 1H
3.99 (d, J = 13.2 Hz, 1 H), 4.58 (AB system, 2J = 11.6 Hz, δa –
δb = 25.4 Hz, 2 H), 7.28–7.38 (m, 10 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 19.0, 36.7, 57.9, 59.3 (2 peaks), 71.9, 72.0, 88.3, 127.2,
2
NMR (300 MHz, CDCl3): δ = 0.82 (t, 3J = 6.8 Hz, 3 H), 1.12–1.46 127.6, 127.7, 128.4 (2 peaks), 128.6, 138.2 ppm. IR (neat): ν = 3438
˜
(m, 14 H), 1.87–1.97 (m, 1 H), 2.48 (AB part of an ABX system,
(O–H), 1602 (C=C), 1264 (C–O) cm–1. MS (DCI/NH3): m/z (%) =
2J ≈ J ≈ 9.2, J = 2.8 Hz, δa – δb = 38.8 Hz, 2 H), 2.92 (dd, J =
312 (100) [MH]+. HRMS (ESI+): calcd. for C20H26NO2 312.1964;
3
3
3
3
2
3
8.3, J = 6.0 Hz, 1 H), 3.07 (d, J = 13.4 Hz, 1 H), 3.45 (dd, J = found 312.1966.
6.0, 3J = 4.0 Hz, 1 H), 3.91 (d, 2J = 13.4 Hz, 1 H), 4.51 (AB system,
[(2S,3R,4S)-1-Benzyl-3-(benzyloxy)-4-butylpyrrolidin-2-yl]methanol
2J = 11.7 Hz, δa – δb = 26.2 Hz, 2 H), 5.18 (dd, 3J = 10.1, 2J =
(37): Vinylpyrrolidine 31 (67.5 mg, 0.19 mmol) was treated accord-
ing to general procedure B. The crude product was purified by flash
column chromatography on silica gel (petroleum ether/EtOAc,
90:10 to 60:40, 0.3% NH4OH) to give 37 (42.0 mg, 63%) as a color-
less oil. Rf = 0.26 (petroleum ether/EtOAc, 80:20, 0.8% NH4OH).
[α]2D5 = +23 (c = 0.9, CHCl3). 1H NMR (300 MHz, CDCl3): δ =
3
2
3
1.8 Hz, 1 H), 5.33 (dd, J = 17.2, J = 1.8 Hz, 1 H), 5.82 (ddd, J
= 17.2, J = 10.1, J = 8.3 Hz, 1 H), 7.13–7.31 (m, 10 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 14.1, 22.6, 28.0, 29.3, 29.5, 29.6, 31.9,
34.3, 43.2, 56.5, 57.2, 71.9, 74.4, 89.7, 118.1, 126.6, 127.5, 127.7,
3
3
128.1, 128.3, 128.6, 138.6, 139.3, 139.8 ppm. IR (neat): ν = 1654,
˜
1601 (C=C) cm–1. MS (ESI+): m/z (%) = 406 (100) [MH]+. HRMS
3
0.90 (t, J = 6.9 Hz, 3 H), 1.20–1.53 (m, 6 H), 2.00–2.09 (m, 1 H),
2.67–2.76 (m, 3 H), 3.37 (d, J = 13.2 Hz, 1 H), 3.70 (AB part of
(ESI+): calcd. for C28H40NO 406.3110; found 406.3109.
2
an ABX system, 2J = 11.2, 3J = 3.5, 3J = 1.9 Hz, δa – δb = 34.9 Hz,
2 H), 3.76–3.79 (m, 1 H), 3.97 (d, 2J = 13.2 Hz, 1 H), 4.57 (AB
system, 2J = 11.6 Hz, δa – δb = 23.5 Hz, 2 H), 7.26–7.41 (m, 10
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.0, 22.7, 30.2, 33.1,
42.6, 57.6, 57.9, 59.3, 71.7, 71.8, 87.0, 127.1, 127.6, 127.7, 128.4 (2
(2S,3R,4S)-1-Benzyl-3-(benzyloxy)-4-phenyl-2-vinylpyrrolidine (18):
Secondary alcohol 16 (50.2 mg, 0.18 mmol) was treated according
to general procedure C. The crude product was purified by flash
column chromatography on silica gel (petroleum ether/EtOAc, 99:1
to 98:2) to give 18 (60.2 mg, 90%) as a white solid. Rf = 0.25 (petro-
leum ether/EtOAc, 98:2). [α]2D5 = –5 (c = 1.0, CHCl3). 1H NMR
peaks), 128.5, 138.3, 138.7 ppm. IR (neat): ν = 3440 (O–H), 1605
˜
(C=C), 1071 (C–O) cm–1. MS (DCI/NH3): m/z (%) = 354 (100)
[MH]+. HRMS (ESI+): calcd. for C23H32NO2 354.2433; found
354.2432.
2
3
(300 MHz, CDCl3): δ = 2.89 (AB part of an ABX system, J = J
3
= 9.4, J = 3.6 Hz, δa – δb = 38.5 Hz, 2 H), 3.09–3.14 (m, 1 H),
3
3.15 (d, 2J = 13.3 Hz, 1 H), 3.28–3.34 (m, 1 H), 3.89 (dd, J = 6.7,
2
2
3J = 4.6 Hz, 1 H), 4.11 (d, J = 13.3 Hz, 1 H), 4.50 (AB system, J
[(2S,3R,4S)-1-Benzyl-3-(benzyloxy)-4-octylpyrrolidin-2-yl]methanol
(38): Vinylpyrrolidine 32 (203.6 mg, 0.50 mmol) was treated ac-
cording to general procedure B. The crude product was purified by
flash column chromatography on silica gel (petroleum ether/
EtOAc, 90:10, 0.4% NH4OH to 80:20, 1.2% NH4OH) to give 38
(117.3 mg, 57%) as a colorless oil. Rf = 0.48 (petroleum ether/
EtOAc, 80:20, 1.2% NH4OH). [α]2D5 = +16 (c = 1.2, CHCl3). 1H
NMR (300 MHz, CDCl3): δ = 0.81 (t, 2J = 6.9 Hz, 3 H), 1.10–1.39
(m, 14 H), 1.90–1.98 (m, 1 H), 2.56–2.65 (m, 3 H), 3.26 (d, 2J =
13.2 Hz, 1 H), 3.54 (dd, 2J = 11.2, 3J = 1.8 Hz, 1 H), 3.64–3.68 (m,
= 11.8 Hz, δa – δb = 22.8 Hz, 2 H), 5.31 (dd, 3J = 10.2, 2J = 1.8 Hz,
3
2
4
1 H), 5.47 (ddd, J = 17.2, J = 1.8, J = 0.4 Hz, 1 H), 5.95 (ddd,
3J = 17.2, J = 10.2, J = 8.3 Hz, 1 H), 7.17–7.39 (m, 15 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 49.7, 57.6, 59.2, 72.2, 74.6, 92.1,
118.7, 126.1, 126.7, 127.4, 127.5, 127.6, 128.1, 128.2, 128.4, 128.6,
3
3
138.2, 139.0, 139.1, 145.8 ppm. IR (neat):
ν = 1632, 1598
˜
(C=C) cm–1. MS (ESI+): m/z (%) = 370 (100) [MH]+. HRMS
(ESI+): calcd. for C26H28NO 370.2171; found 370.2151.
(2S,3S,4S)-1-Benzyl-3-(benzyloxy)-4-(octyloxy)-2-vinylpyrrolidine
(33): Secondary alcohol 8 (75.6 mg, 0.23 mmol) was treated accord-
ing to general procedure C. The crude product was purified by flash
column chromatography on silica gel (petroleum ether/EtOAc, 99:1
to 95:5) to give 33 (69.1 mg, 79%) as a colorless oil. Rf = 0.48
2
2
2 H), 3.87 (d, J = 13.2 Hz, 1 H), 4.46 (AB system, J = 11.6 Hz,
δa – δb = 26.3 Hz, 2 H), 7.15–7.34 (m, 10 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 14.1, 22.6, 28.0, 29.2, 29.5, 29.6, 31.8, 33.4,
42.6, 57.6, 57.9, 59.3, 71.7, 71.8, 87.1, 127.1, 127.6, 127.7, 128.4 (2
peaks), 128.5, 138.3, 138.7 ppm. IR (neat): ν = 3445 (O–H), 1605
1
˜
(petroleum ether/EtOAc, 90:10). [α]2D5 = +77 (c = 1.3, CHCl3). H
(C=C), 1071 (C–O) cm–1. MS (ESI+): m/z (%) = 410 (100) [MH]+.
NMR (300 MHz, CDCl3): δ = 0.82 (t, 3J = 7.0 Hz, 3 H), 1.14–1.30
HRMS (ESI+): calcd. for C27H40NO2 410.3059; found 410.3067.
2
3
(m, 10 H), 1.42–1.51 (m, 2 H), 2.36 (dd, J = 10.5, J = 6.1 Hz, 1
2
H), 2.80–2.88 (m, 2 H), 3.05 (d, J = 13.4 Hz, 1 H), 3.20–3.33 (m,
[(2S,3R,4S)-1-Benzyl-3-(benzyloxy)-4-phenylpyrrolidin-2-yl]metha-
nol (39): Vinylpyrrolidine 18 (80.8 mg, 0.22 mmol) was treated ac-
cording to general procedure B. The crude product was purified by
flash column chromatography on silica gel (petroleum ether/
EtOAc, 90:10, 0.4% NH4OH) to give 39 (45.1 mg, 56%) as a color-
less oil. Rf = 0.37 (petroleum ether/EtOAc, 80:20, 0.8% NH4OH).
[α]2D5 = +24 (c = 1.1, CHCl3). 1H NMR (300 MHz, CDCl3): δ =
2.82–2.86 (m, 1 H), 2.97–3.09 (m, 2 H), 3.25–3.32 (m, 1 H), 3.40
(d, 2J = 13.1 Hz, 1 H), 3.72 (AB part of an ABX system, 3J = 11.4,
2 H), 3.73–3.75 (m, 2 H), 3.93 (d, 2J = 13.4 Hz, 1 H), 4.56 (s, 2 H),
5.22 (dd, 3J = 10.1, 2J = 1.5 Hz, 1 H), 5.33 (dd, 3J = 17.3, 2J =
1.5 Hz, 1 H), 5.85 (ddd, 3J = 17.3, 3J = 10.1, 3J = 8.7 Hz, 1 H),
7.14–7.28 (m, 10 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.1,
22.6, 26.1, 29.2, 29.4, 29.7, 31.8, 56.7, 57.2, 69.5, 72.1, 72.8, 82.9,
89.2, 119.1, 126.8, 127.5, 127.7, 128.1, 128.2, 128.9, 138.2, 138.3,
138.7 ppm. IR (neat): ν = 1643, 1605 (C=C), 1099 (C–O) cm–1.
˜
MS (ESI+): m/z (%) = 423 (100) [MH]+. HRMS (ESI+): calcd. for
3
2
3J = 3.5 Hz, J = 2.1 Hz, ∆δa – δb = 32.8 Hz, 2 H), 4.03 (d, J =
13.1 Hz, 1 H), 4.03 (dd, 3J = 6.2, 3J = 4.9 Hz, 1 H), 4.44 (AB
system, 2J = 11.5 Hz, δa – δb = 53.6 Hz, 2 H), 7.14–7.37 (m, 15
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 48.8, 58.3, 59.3, 59.6,
71.3, 72.4, 88.1, 126.4, 127.3, 127.7, 128.4, 128.5, 128.7, 138.0,
C28H40NO2 422.3059; found 422.3077.
[(2S,3R,4S)-1-Benzyl-3-(benzyloxy)-4-methylpyrrolidin-2-yl]metha-
nol (36): Vinylpyrrolidine 30 (83.0 mg, 0.27 mmol) was treated ac-
cording to general procedure B. The crude product was purified by
flash column chromatography on silica gel (petroleum ether/iPrOH,
95:5 to 90:10, 0.15% Et3N) to give 36 (53.1 mg, 63%) as a colorless
138.2, 144.1 ppm. IR (neat): ν = 3472 (O–H), 1644, 1605 (C=C),
˜
1071 (C–O) cm–1. MS (ESI+): m/z (%) = 374 (100) [MH]+. HRMS
oil. Rf = 0.23 (petroleum ether/iPrOH, 90:10, 0.15% Et3N). [α]2D5
=
(ESI+): calcd. for C25H28NO2 374.2120; found 374.2109.
1
+26 (c = 1.4, CHCl3). H NMR (300 MHz, CDCl3): δ = 1.09 (d,
3J = 7.2 Hz, 3 H), 2.17–2.29 (m, 1 H), 2.64–2.79 (m, 3 H), 3.39 (d,
2J = 13.2 Hz, 1 H), 3.71–3.73 (m, 1 H), 3.72 (AB part of an ABX
[(2S,3S,4S)-1-Benzyl-3-(benzyloxy)-4-(octyloxy)pyrrolidin-2-yl]meth-
anol (40): Vinylpyrrolidine 33 (69.0 mg, 0.16 mmol) was treated ac-
system, J = 11.3, J = 3.5, J = 1.8 Hz, δa – δb = 32.4 Hz, 2 H), cording to general procedure B. The crude product was purified by
2
3
3
2486 Eur. J. Org. Chem. 2009, 2474–2489
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim