B. H. Kim et al. / Tetrahedron: Asymmetry 16 (2005) 1215–1220
1219
than 2–5% by GC analysis. The reaction mixture was
then concentrated and chromatographed with SiO2 to
give the addition product.
(m, 4H), 4.00–4.18 (m, 2H); 13C NMR (125 MHz, major
conformer): d 12.2, 12.5, 16.9, 17.7, 23.9, 24.0, 28.2, 28.4,
30.9, 31.0, 32.6, 33.4, 38.8, 38.9, 47.2, 48.5, 48.6, 54.6,
54.7, 56.8, 56.9, 173.3, 173.7, 196.4, 196.5; MS (EI) m/z
300 (M+, 2), 152 (3), 86 (100); HRMS (EI) calcd for
C15H28N2O2S 300.1872, found 300.1859.
4.2.1. (S)-Acetylcaptopril 2a and 1-((20R)-30-acetylthio-
20-methylpropanoyl)-L-proline 3a. Viscous oil (2.1 g,
86%). Rf = 0.05 (hexane–EtOAc–AcOH 15:5:1) or 0.7
(CH2Cl2–MeOH–AcOH 8:1:1); IR (film) 2978 (br),
4.2.5. (2S)-1-((20S)-30-Acetylthio-20-methylpropanoyl)-2-
(benzylaminomethyl)pyrrolidine 2e and (2S)-1-((20R)-30-
acetylthio-20-methylpropanoyl)-2-(benzylaminomethyl)-
pyrrolidine 3e. Colorless oil (139 mg, 62%). Rf = 0.70
(CHCl3–MeOH–aq NH3 80:18:2); IR (film) 2969,
1
1744, 1691, 1622, 1610, 1446, 1190 cmꢀ1; H NMR d
1.02 (d, 3H, J = 6.8), 1.08 (d, 3H, J = 6.8), 1.13 (m,
2H), 1.27–1.64 (m, 4H), 1.79–1.91 (m, 2H), 1.82 (s,
3H), 1.86 (s, 3H), 2.55–2.69 (m, 3H), 2.87–2.99 (m,
4H), 3.11–3.33 (m, 3H), 4.33 (dd, 1H, J = 3.1, 8.4),
4.43 (dd, 1H, J = 3.7, 8.4), 8.77 (br s, 2H); 13C NMR
(C6D6, 60 ꢁC, the major conformer): d 16.2, 16.6, 24.7,
24.8, 28.5, 28.6, 30.1, 32.6, 32.9, 38.6, 38.7, 47.2, 47.3,
59.5, 59.7, 173.5, 173.8, 174.8, 174.9, 196.1, 196.2; MS
(EI) m/z 259 (M+, 2), 216 (39), 172 (52), 114 (33), 70
(100); HRMS (CI) calcd for C11H18NO4S 260.0957,
found 260.0957.
1694, 1645, 1428, 1135, 627 cmꢀ1
;
1H NMR
(500 MHz): d 1.07 (d, 3H, J = 6.8), 1.09 (d, 3H,
J = 6.8), 1.69–2.30 (m, 16H), 2.65–3.03 (m, 6H), 3.20–
3.64 (m, 6H), 4.24–4.69 (m, 6H), 7.02–7.35 (m, 10H);
13C NMR (the major conformer) d 16.3, 21.3, 21.5,
23.6, 27.7, 27.9, 30.2, 32.2, 32.7, 38.1, 46.3, 47.0, 51.8,
51.9, 54.5, 55.4, 126.2, 127.1, 128.6, 137.2, 171.4,
173.2, 195.2, 195.3; MS (EI) m/z 333 (M+, 31), 214
(37), 145 (39), 91 (44), 70 (100); HRMS (EI) calcd for
C18H25N2O2S 333.1637, found 333.1639.
4.2.2. (S)-Acetylcaptopril methyl ester 2b and 1-((20R)-30-
acetylthio-20-methylpropanoyl)-L-proline methyl ester
3b. Colorless oil (151 mg, 95%). Rf = 0.3 (hexane–
EtOAc–AcOH 15:5:1); IR (film) 1747, 1690, 1651,
4.2.6. (2R,5R)-1-((20S)-30-Acetylthio-20-methylpropan-
oyl)-2,5-bis(methoxymethyl)pyrrolidine 5b and its enan-
tiomer 6a. Colorless oil (180 mg, 89%). Rf = 0.65
(CH2Cl2–MeOH 20:1); IR (film) 1692, 1639, 1422,
1430, 1198 cmꢀ1 1H NMR (C6D6): d 1.11 (d, 3H,
;
J = 6.8), 1.16 (d, 3H, J = 6.8), 1.17 (m, 2H), 1.51 (m,
6H), 1.83 (s, 3H), 1.85 (s, 3H), 2.67–2.82 (m, 3H), 3.06
(m, 3H), 3.25–3.48 (m, 4H), 3.31 (s, 3H), 3.36 (s, 3H),
4.47 (dd, 1H, J = 4.4, 8.0), 4.53 (t, 1H, J = 6.0); 13C
NMR (CDCl3, 60 ꢁC, the major conformer): 16.2,
16.5, 24.6, 24.7, 28.8, 28.9, 30.3, 32.2, 32.5, 38.0, 38.2,
46.7, 46.8, 51.7, 58.5, 58.7, 172.3, 172.4, 173.1, 195.5;
MS (EI) m/z 273 (M+, 9), 230 (63), 214 (34), 128 (38),
70 (100); HRMS (EI) calcd for C12H19NO4S 273.1035,
found 273.1020.
1
1114 cmꢀ1; H NMR d 1.21 (d, 3H, J = 6.1), 1.93 (m,
3H), 2.13 (m, 1H), 2.34 (s, 3H), 2.95 (m, 3H), 3.21 (d,
2H, J = 6.6), 3.28–3.38 (m, 1H), 3.32 (s, 3H), 3.35 (s,
3H), 3.60 (dd, 1H, J = 3.1, 9.2), 4.11 (q, 1H, J = 7.1),
4.24 (m, 1H); 13C NMR d 17.0, 25.1, 26.8, 30.4, 33.9,
38.0, 56.8, 57.2, 58.6, 58.9, 70.9, 74.3, 174.1, 195.7; MS
(EI) m/z 258 (M+ꢀMeOCH2, 67), 216 (4), 145 (13),
19
114 (100); 5b: ½a ¼ ꢀ46:6 (c 1.01, CHCl3), 6a:
D
24
D
C14H26NO4S 304.1583, found 304.1578.
½a ¼ þ45:9 (c 1.01, CHCl3); HRMS (CI) calcd for
4.2.3. S-Acetylcaptopril phenyl ester 2c and 1-((20R)-30-
acetylthio-20-methylpropanoyl)-L-proline phenyl ester
3c. Colorless oil (202 mg, 90%). Rf = 0.3 (hexane–
EtOAc–AcOH 15:5:1); IR (film) 1767, 1695, 1652,
4.2.7. (S,S)-N-((20S)-30-Acetylthio-20-methylpropanoyl)-
N,N-bis(phenylethyl)amine 5c and (S,S)-N-((20R)-30-acet-
ylthio-20-methylpropanoyl)-N,N-bis(phenylethyl)amine
6c. Colorless oil (99 mg, 40%). Rf = 0.70 (CH2Cl2–
MeOH 20:1); IR (film) 1689, 1634, 1435, 1137, 701,
1429, 1195, 690, 627 cmꢀ1 1H NMR d 1.23 (d, 3H,
;
1
627 cmꢀ1; H NMR d 0.52 (br d, 3H, J = 6.2), 1.17 (br
J = 6.4), 1.24 (d, 3H, J = 6.4), 2.00–2.50 (m, 8H), 2.25
(s, 3H), 2.32 (s, 3H), 2.76–3.03 (m, 4H), 3.18 (m, 2H),
3.54–3.69 (m, 3H), 3.86 (m, 1H), 4.67 (dd, 1H, J = 4.0,
8.3), 4.72 (dd, 1H, J = 4.1, 8.4), 7.05–7.38 (m, 10H);
13C NMR (60 ꢁC, the major conformer): d 16.3, 16.5,
24.8, 28.9, 29.0, 30.2, 30.3, 32.2, 32.5, 38.0, 38.2, 46.7,
46.8, 58.8, 59.1, 121.2, 121.3, 125.5, 129.0, 129.1,
150.8, 170.4, 170.5, 173.3, 195.4; MS (EI) m/z 292
(M+ꢀCH3CO, 5), 242 (M+ꢀOPh, 100), 214 (44), 145
(39), 70 (90); HRMS (CI) calcd for C17H22NO4S
336.1270, found 336.1276.
d, 3H, J = 6.4), 1.63 (d, 3H, J = 7.1), 1.64 (d, 3H,
J = 7.1), 1.68 (d, 3H, J = 7.1), 1.71 (d, 3H, J = 7.1),
2.17 (s, 3H), 2.26 (s, 3H), 2.60 (m, 1H), 2.70–2.88 (m,
4H), 3.05 (dd, 1H, J = 7.7, 13.2), 4.80 (br q, 1H,
J = 7.1), 4.92 (br q, 1H, J = 7.1), 5.20 (br s, 1H), 5.77
(br s, 1H), 6.77–7.23 (m, 20H); 13C NMR (60 ꢁC): d
16.7, 19.5, 30.3, 32.9, 33.7, 38.0, 38.6, 52.7, 53.5, 127.2,
128.1, 128.4, 128.6, 140.9, 141.5, 175.1, 175.6, 195.3,
195.8; MS (EI) m/z 264 (M+ꢀCH(Ph)CH3, 70), 145
(15), 120 (100), 105 (94); HRMS (CI) calcd for
C22H28NO2S 370.1841, found 370.1836.
4.2.4. (2S)-1-((20S)-30-Acetylthio-20-methylpropanoyl)-2-
(diethylaminomethyl)pyrrolidine 2d and (2S)-1-((20R)-30-
acetylthio-20-methylpropanoyl)-2-(diethylaminomethyl)-
pyrrolidine 3d. Colorless oil (105 mg, 52%). Rf = 0.70
(CHCl3–MeOH–aq NH3 80:18:2); IR (film) 1694, 1652,
4.2.8.
(2S,5S)-1-((20S)-30-Acetylthio-20-methylpropa-
noyl)-2,5-dimethylpyrrolidine 5d. Colorless oil (134 mg,
82%). Rf = 0.40 (hexane–EtOAc–AcOH 15:5:1); IR
(film) 1692, 1637, 1463, 1136 cmꢀ1 1H NMR d 1.12
;
1
1429, 795, 627 cmꢀ1; H NMR (500 MHz): d 0.87–1.04
(d, 3H, J = 6.5), 1.17 (d, 3H, J = 6.5), 1.21 (d, 3H,
J = 6.6), 1.51–1.65 (m, 2H), 2.02–2.30 (m, 2H), 2.34 (s,
3H), 2.80 (m, 1H), 2.94 (dd, 1H, J = 6.8, 13.2), 3.07
(dd, 1H, J = 7.9, 13.2), 4.12 (qn, 1H, J = 6.5), 4.24
(m, 12H), 1.06–1.23 (m, 6H), 1.85–1.99 (m, 8H), 2.10–
2.33 (m, 3H), 2.27 (s, 3H), 2.29 (s, 3H), 2.34–2.55 (m,
6H), 2.56–2.80 (m, 5H), 2.83–3.16 (m, 4H), 3.30–3.59