V. K. Aggarwal et al. / Tetrahedron: Asymmetry 13 (2002) 87–93
91
flask flushed with N2. NaH (60% in oil, 200 mg, 5.00
mmol) was then introduced carefully in one portion.
The solution was stirred for 1.5 h at room temperature
then MeI (0.24 mL, 4.00 mmol) was added. The mix-
ture was heated under reflux for 15 h. Excess NaH was
hydrolysed with aqueous NH4Cl solution. The organic
layer was separated and the aqueous layer extracted
with ethyl acetate (3×50 mL). The combined extracts
were washed with brine (2×20 mL) and dried over
Na2SO4. After filtration, the solvent was removed by
rotary evaporator affording a white solid. Column
chromatography on silica gel (EtOAc/petroleum ether;
20/80) afforded (S,S)-13a (710 mg, 83%) as a white
solid: Rf=0.67; mp 71–72°C; [h]2D2 −78.6 (c 1.50 in
NMR (250 MHz, CDCl3): lH=1.00–1.50 (m, 4H,
CH2ꢀCH2), 1.95 (br s, 1H, NH), 2.98 (s, 6H, 2×OCH3),
3.71–3.82 (m, 2H, 2×CH), 7.21–7.44 (m, 20H, aromatic
H). 13C NMR (62.9 MHz, CDCl3): lC=26.8 (2×CH2),
51.4 (2×OCH3), 62.3 (2×CH), 85.7 (2×COCH3), 127.0,
127.1, 127.2, 127.5, 129.2, 129.5 (aromatic C), 141.5,
142.7 (aromatic q. C). IR (KBr disc): 3056, 2988, 2903
(CH), 1492, 1445, 1075, 757, 701 cm−1. MS (CI): m/z
(rel. intensity)=464 ([M++1], 61), 266 (53), 234 (80),
197 (100), 131 (68), 105 (70), 77 (33). Elemental analy-
sis: C32H33NO2 requires: C, 82.90; H, 7.17; N, 3.02.
Found: C, 82.88; H, 7.25; N, 2.86%.
4.6. 1-[(S)-1-Phenylethyl]-trans-(2S,5S)-(1-hydroxy-1,1-
diphenylmethyl)-(1-trimethylsilyloxy-1,1-diphenyl-
methyl)pyrrolidine 14a
1
CHCl3). H NMR (250 MHz, CDCl3): lH=1.10–1.25
(br s, 3H, CHCH3), 1.50–4.00 (br s, 12H), 4.60–4.80 (br
1
s, 1H, CHCH3), 6.95–7.67 (m, 25H, aromatic H). H
NMR (400 MHz, DMSO at 80°C): lH=1.18 (d, 3H,
CHCH3, J=6.7 Hz), 1.60–1.87 (m, 4H, CH2CH2), 2.63
(br s, 6H, 2×OCH3), 3.71 (br s, 2H, 2×CH), 4.63 (q,
1H, CHCH3, J=6.7 Hz), 7.05–7.40 (m, 25H, aromatic
H). 13C NMR (400 MHz, DMSO at 80°C): lC=16.1
(CHCH3), 28.5 (2×CH2), 52.2 (CHCH3), 55.8 (2×
OCH3), 67.5 (2×CH), 86.3 (2×CPh2), 125.7, 126.9,
127.1, 127.5, 129.0, 129.1, 129.8 (aromatic C), 142.9,
143.1, 146.1 (aromatic q. C). IR (KBr disc): 3057, 3025,
2935 (CH); 1493, 1447, 1074, 746, 701 cm−1. MS (FAB):
m/z (rel. intensity)=568 ([M++1], 14), 370 (100), 234
(23), 197 (30), 131 (40). Elemental analysis: C40H41NO2
requires C, 84.62; H, 7.28; N, 2.47. Found C, 84.48; H,
7.43; N, 2.31%. The compound resulting from mono-
alkylation was isolated as a white solid (113 mg, 13%):
Rf=0.41; mp 69–72°C; [h]2D2 −90.5 (c 1.47 in CHCl3).
1H NMR (250 MHz, CDCl3): lH=1.21 (d, 3H,
CHCH3, J=6.4 Hz), 1.60–2.00 (m, 4H, CH2CH2), 2.76
(s, 3H, OCH3), 3.10 (br s, 1H, OH), 3.51–3.80 (m, 2H,
2×CH), 4.55 (q, 1H, CHCH3, J=6.4 Hz), 6.55–6.75 (m,
2H, aromatic H), 6.90–7.65 (m, 23H, aromatic H). 13C
NMR (62.9 MHz, CDCl3): lC=15.4 (CHCH3), 27.4
and 28.8 (2×CH2), 53.0 (CHCH3), 55.5 (OCH3), 66.9
and 67.8 (2×CHN), 78.5 [C(OH)], 85.2 (COCH3),
126.5, 126.6, 126.7, 126.8, 126.9, 127.0, 127.1, 127.4,
127.5, 127.6, 127.8, 127.9, 128.2, 128.8, 129.1 (aromatic
C), 143.1, 143.7, 145.3, 146.0, 146.8 (aromatic q. C). IR
(KBr disc): 3057, 3024, 2987 (CH), 1493, 1447, 1075,
756, 700 cm−1. MS (FAB): m/z (rel. intensity)=554
([M++1], 49), 370 (100), 356 (77), 234 (41), 197 (33).
Elemental analysis: C39H39NO2 requires C, 84.59; H,
7.10; N, 2.53. Found C, 84.41; H, 7.23; N, 2.38%.
To a stirred solution of diol (S,S)-12a (270 mg, 0.50
mmol), 1,8-bis(dimethylaminonaphthalene) (236 mg,
1.10 mmol), triethylsilane (1.58 mL, 5.00 mmol) and
anhydrous CH2Cl2 (1.5 mL) was added and trimethyl-
silyl triflate (0.20 mL, 1.10 mmol) dropwise under nitro-
gen. The mixture was stirred at room temperature for 3
h and then neutralised with a mixture of CH2Cl2 (40
mL) and Et3N (0.4 mL). The solvent was removed
under reduced pressure to obtain a yellow solid, which
was purified by column chromatography on silica gel
(EtOAc/petroleum ether; 15/85). The first compound
eluted was the corresponding double-silylated com-
pound 14b (125 mg, 36%) as a white solid. Rf=0.80;
1
mp 73–75°C; [h]2D2 +37.9 (c 1.53 in CHCl3). H NMR
(300 MHz, CDCl3, TMS): lH=−0.38 (s, 9H, OSiCH3),
0.00 (s, 9H, OSiMe3), 1.35–1.54 [m, 4H, CH3 and
CH(H)], 2.10–2.26 [m, 3H, CH2 and CH(H)], 4.05–4.17
(m, 1H, NCH), 4.30–4.38 (m, 1H, NCH), 4.45 (q, 1H,
CHCH3, J=6.6 Hz), 6.64–7.35 (m, 23H, aromatic H),
7.75–7.74 (m, 2H, aromatic H). 13C NMR (75.5 MHz,
CDCl3, TMS): lC=1.8 and 2.5 (2×SiMe3), 17.4 (CH3),
28.8 and 29.0 (CH2ꢀCH2), 55.2 (CHCH3), 67.4 and 70.9
(2×CHN), 84.5 and 87.7 (2×COSiMe3), 124.6, 125.7,
126.5, 126.8, 127.1, 127.4, 127.6, 127.7, 128.6, 129.3,
130.4, 144.6 (aromatic C), 145.5, 146.7, 147.1, 148.4
(aromatic q. C). IR (KBr disc): 3059, 2958, 1493, 1445,
1252, 1117, 1060, 881, 838, 700 cm−1. MS (CI): m/z (rel.
intensity)=684 ([M++1], 22), 668 (48), 428 (85), 308
(29), 255 (100), 234 (32), 131 (46), 105 (60), 91 (21), 73
(35). Elemental analysis: C44H53NO2Si2 requires: C,
77.25; H, 7.81; N, 2.05. Found: C, 77.66; H, 7.81; N,
1.88%. The corresponding monosilylated compound
14a was obtained as a white solid (160 mg, 52%).
Rf=0.45; mp 69–72°C; [h]2D2 −38.8 (c 1.58 in CHCl3).
1H NMR (270 MHz, CDCl3, TMS): lH=0.00 (s, 9H,
SiMe3), 1.54 (d, 3H, CH3, J=6.8 Hz), 1.70–1.86 (m,
1H, CH(H)), 2.10–2.37 (m, 3H, CH2 and CH(H)), 3.47
(br s, 1H, OH), 3.50–3.63 (m, 1H, NCH), 4.16–4.27 (m,
1H, NCH), 4.54 (q, 1H, CHCH3, J=6.8 Hz), 6.51–6.61
(m, 2H, aromatic H), 6.86–6.98 (m, 2H, aromatic H),
7.06–7.56 (m, 21H, aromatic H). 13C NMR (67.9 MHz,
CDCl3, TMS): lC=2.6 (SiMe3), 16.3 (CH3), 27.4 and
28.9 (CH2CH2), 55.1 (CHCH3), 67.9 and 69.4 (CHN),
78.5 [C(OH)], 84.4 (COSi), 126.3, 126.5, 126.6, 126.7,
126.8, 127.4, 127.43, 127.5, 127.60, 127.62, 127.7, 127.9,
128.1 (aromatic C), 144.7, 146.2, 146.5, 146.8, 146.9
4.5. trans-(2S,5S)-Bis(1-methoxy-1,1-diphenylmethyl)-
pyrrolidine 13
A solution of (S,S)-13a (1.00 g, 1.76 mmol) in MeOH
(30 mL) was hydrogenated over 20% Pd(OH)2/C (325
mg). The air was removed gently by vacuum before
introducing H2 and the mixture was then stirred at
room temperature for 48 h. After removing the catalyst
by filtration through Celite, the solvent was removed
under reduced pressure to give a white solid, which was
purified by column chromatography on silica gel
(EtOAc/petroleum ether; 20/80) (680 mg, 83%): Rf=
1
0.50; mp 48–50°C; [h]2D2 −106.6 (c 1.52 in CHCl3). H