B.-Y. He et al. / Tetrahedron: Asymmetry 14 (2003) 2101–2108
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4.12. (4S,5R)-4-Benzyloxy-1-(4-methoxybenzyl)-5-(1-
methylprop-2-enyl)-2-pyrrolidinone, 25 and (3S,5RS)-3-
benzyloxy-1-(1-methoxybenzyl)-5-(1-methylprop-2-enyl)-
2-pyrrolidinone, 26
−41.2 (c 1.2, CHCl3). IR (film) wmax: 2956, 2929, 2857,
1712, 1398, 1345, 1257, 1164, 1147, 1106, 949, 836, 781
cm−1. 1H NMR (500 MHz, CDCl3) l: 0.16 (s, 3H,
CH3), 0.17 (s, 3H, CH3), 0.95 (s, 9H, 3×CH3), 2.60 (dd,
J=18.0, 4.4 Hz, 1H, H-4), 3.00 (dd, J=18.0, 8.1 Hz,
1H, H-4), 4.56 (dd, J=8.1, 4.4 Hz, 1H, H-3), 4.60 (d,
J=14.1 Hz, 1H, PhCH2), 4.68 (d, J=14.1 Hz, 1H,
PhCH2), 7.20–7.40 (m, 5H, Ph) ppm. 13C NMR (125
MHz, CDCl3): 176.99, 174.55, 136.22, 129.48, 128.75,
68.73, 68.53, 43.02, 39.53, 26.28, 18.91, −3.96, −4.59
ppm. MS (ESI, m/z): 342 (M+Na+, 100), 337 (39), 320
(M+H+, 71), 304 (50), 274 (29). Anal. Calcd for
C17H25NO3Si·0.25H2O: C, 63.04; H, 7.94; N, 4.32.
Found: C, 63.39; H, 8.01; N, 4.46.
Following the same procedure described for (+)-13,
namely the treatment of the malimide (S)-10 (219 mg,
0.674 mmol) with freshly prepared crotyl magnesium
chloride at −78°C for 2.5 h, followed by the reaction of
the resulting regio and diastereomeric mixture with
Et3SiH/BF3·OEt2 (−78°C, 8 h; then rt, 32 h), 25 (159
mg, yield 65%) and 26 (72 mg, yield 29%) were
obtained both as a colorless oil. Regioisomer 25 is a
mixture of two diastereomers 25a and 25b (ratio,
68:32): IR (film) wmax: 2962, 2931, 1690, 1513, 1454,
1
1247, 1176, 1090, 1030, 739, 699 cm−1. H NMR (300
4.14. (4S,5R)-4-(tert-Butyldimethylsilyloxy)-1-benzyl-2-
pyrrolidinone, (+)-33 and (3S,5RS)-4-(tert-butyldi-
methylsilyloxy)-1-benzyl-2-pyrrolidinone, 35
MHz, CDCl3) l: 0.84 (d, J=7.0 Hz, 0.96H, CH3C-1%,
25a), 1.02 (d, J=7.0 Hz, 2.04H, CH3C-1%, 25b), 2.71–
2.44 (m, 3H, 2H-3 and H-1%, 25a,b), 3.45 (dd, J=1.1,
3.5 Hz, 0.68 H, H-5, 25a), 3.53 (dd, J=1.1, 4.0 Hz, 0.32
H, H-5, 25b), 3.79 (s, 3H, OCH3, 25a,b), 3.86 (pseudo
dt, overlapped, J=1.1, 6.5 Hz, H-4, 1H, 25a,b), 3.91 (d,
J=15.0 Hz, NCH2-Ph, 25b), 3.92 (d, J=15.0 Hz, over-
lapped with l 3.91, NCH2-Ph, 1H, 25a), 4.31, 4.36 and
4.43, 4.47 (each d, overlapped, J=11.4, 11.71, 11.4,
11.7 Hz, 2H, OCH2-Ph, 25a,b), 5.18–4.90 (m, 3H, 2
H-3% and NCH2), 5.58 (ddd, J=6.6, 10.5, 17.1 Hz, 1H,
H-2%, 25a), 5.72 (ddd, J=6.2, 10.8, 17.0 Hz, 1H, H-2%,
25b), 6.84 (d, J=8.6 Hz, 2H, PMB, 25a,b), 7.40–7.10
(m, 7H, Ph and PMB, 25a,b) ppm. MS (ESI, m/z): 388
(M+Na+, 33), 366 (M+H+, 100), 274 (27). Regioisomer
Following the procedure described for (+)-13, namely
the treatment of the malimide (S)-29 (450 mg, 1.41
mmol) with methyl magnesium iodide at −15°C for 1 h,
followed by the reaction of the resulting regio and
diastereomeric mixture (30 178 mg and 31 135 mg) with
Et3SiH/BF3·OEt2 (−78°C, 4 h; then warm up), 33/34
(136 mg, yield 65%, 33/34=82:28) and 35 (114 mg, as a
3:1 diastereomeric mixture, yield 29%) were obtained. A
sample of pure 33 was obtained after further column
chromatography purification on silica gel. Regioisomer
33: colorless oil. [h]D20=+58.1 (c 1.2, CHCl3). IR (film)
wmax: 2955, 2929, 2856, 1697, 1411, 1252, 1112, 1069,
1
26 is
a
mixture of four diastereomers (ratio,
927, 831, 777 cm−1. H NMR (500 MHz, CDCl3) l:
26a:26b:26c:26d=27:13:18:42): IR (film) wmax: 2961,
−0.01 (s, 3H, CH3), 0.04 (s, 3H, CH3), 0.85 (s, 9H,
3×CH3), 1.11 (d, J=6.6 Hz, 3H, CH3), 2.35 (dd, J=3.3,
16.9 Hz, 1H, H-3), 2.71 (dd, J=6.1, 16.9 Hz, 1H, H-3),
3.32 (dq, J=2.6, 6.6 Hz, 1H, H-5), 3.92 (d, J=15.5 Hz,
1H, PhCH2), 3.97 (m, 1H, H-4), 5.06 (d, J=15.5 Hz,
1H, PhCH2), 7.20–7.40 (m, 5H, Ph) ppm. MS (ESI,
2932, 1693, 1513, 1454, 1304, 1247, 1176, 1109, 1031,
737, 699 cm−1. H NMR (300 MHz, CDCl3) l: 0.79 (d,
1
J=7.0 Hz, 0.81H, CH3C-1%, isomer 26a), 0.81 (d, J=
6.6 Hz, 0.39H, CH3C-1%, isomer 26b), 0.89 (d, J=7.0
Hz, 0.54H, CH3C-1%, isomer 26c), 0.94 (d, J=7.0 Hz,
1.26H, CH3C-1%, isomer 26d), 1.86 (m, 1H, H-4, 4
isomers), 2.05 (m, 1H, H-4, 4 isomers), 2.80–2.50 (m,
1H, H-1%, 4 isomers), 3.60–3.41 (m, 1H, H-5, 4 isomers),
3.78 (m, 3H, OCH3, 4 isomers), 3.86 (m, 1H, NCH2, 4
isomers), 4.15 (m, 1H, H-3, 4 isomers), 4.76 (m, 1H,
OCH2-Ph, 4 isomers), 5.04 (m, 4H, 2 H-8, NCH2 and
OCH2-Ph, 4 isomers), 5.59 (m, 1H, H-7), 6.80 (m, 2H,
PMB, 4 isomers), 7.40–7.10 (m, 7H, Ph and PMB, 4
isomers) ppm. MS (ESI, m/z): 388 (M+Na+, 19), 366
(M+H+, 100), 274 (15).
m/z): 321 (M++H, 100), 278 (7), 254 (6), 92 (PhCH2 ,
+
3). Regioisomer 35 (as a 3:1 diastereomeric mixture):
colorless oil. IR (film) wmax: 2950, 2929, 2856, 1704,
1420, 1361, 1253, 1144, 1080, 984, 837, 779, 701 cm−1.
1H NMR (500 MHz, CDCl3): major diastereomer l:
0.18 (s, 3H, CH3), 0.20 (s, 3H, CH3), 0.93 (s, 9H,
3×CH3), 1.12 (d, J=8.4 Hz, 3H, CH3), 1.88 (m, 1H,
H-4), 2.04 (m, 1H, H-4), 3.57 (m, 1H, H-5), 3.97 (d,
J=15.0 Hz, 1H, PhCH2), 4.41 (t, J=6.4 Hz, 1H, H-3),
4.97 (d, J=15.0 Hz, 1H, PhCH2), 7.20–7.40 (m, 5H,
Ph) ppm; minor diastereomer l: 0.17 (s, 3H, CH3), 0.20
(s, 3H, CH3), 0.94 (s, 9H, 3×CH3), 1.21 (d, J=6.4 Hz,
3H, CH3), 1.56 (m, 1H, H-4), 2.43 (m, 1H, H-4), 3.37
(m, 1H, H-5), 4.04 (d, J=14.9 Hz, 1H, PhCH2), 4.37 (t,
J=7.8 Hz, 1H, H-3), 4.96 (d, J=14.9 Hz, 1H, PhCH2),
7.20–7.40 (m, 5H, Ph) ppm. MS (ESI, m/z): 321 (M++
H, 100), 305 (20).
4.13. (S)-1-Benzyl-3-(tert-butyldimethylsilyloxy)pyrro-
lidine-2,5-dione, (−)-29
A mixture of (S)-1-benzylmalimide12a,b (270 mg, 1.32
mmol), TBDMSCl (250 mg, 1.67 mmol), imidazole (234
mg, 3.44 mmol) and DMF (1 mL) was stirred at 40°C
for 24 h and quenched with glacial H2O (1 mL). The
resulting mixture was extracted with Et2O (3×10 mL).
The combined organic layers were washed with brine,
dried over Na2SO4, and evaporated under reduced pres-
sure. The residual oil was purified by column chro-
matography on silica gel to provide compound 29 (302
mg, 94% based on the recovered staring material, 63
mg, 12%) as a white solid. Mp 75.5–77.0°C. [h]2D0=
Acknowledgements
The authors are grateful to the NNSF of China and the
Fund for doctoral sites of the Ministry of Education for
financial support.