N-(α-Chloroalkyloxycarbonyl)pyrrolidines as a Source of Oxygenated d1-Reagents
FULL PAPER
CH2NCH2), 3.47 (d, J ϭ 3.1 Hz, 1 H, CHOH), 4.97 (qd, J ϭ 6.5,
3.1 Hz, 1 H, CH3CH). Ϫ 13C NMR: δ ϭ 16.0 (CH3CH), 25.55, 1.75Ϫ1.90 (m,
25.65 (CH2CH2CH2N), 26.6 [(CH3)3C], 34.3 [(CH3)3C], 45.95, 46.1
NMR: δ ϭ 1.16 (d, J ϭ 6.1 Hz, 3 H, CH3CH), 1.55 (s, 3 H, CH3C),
H, CH2CH2CH2N), 3.10Ϫ3.35 [m, H,
CH2NCH2, OH], 5.05 (q, J ϭ 6.1 Hz, 1 H, CH), 7.18Ϫ7.57 (m, 5
4
5
(CH2NCH2), 72.75 (CH3CH), 80.75 (CHOH), 154.5 (CO2). Ϫ GC- H, ArH). Ϫ 13C NMR: δ ϭ 15.4 (CH3CH), 24.1 (CH3C), 24.7,
LRMS: m/z (%) ϭ 172 [Mϩ Ϫ (CH3)3C, 8], 143 (11), 116 (52), 114 25.5 (CH2CH2CH2N), 45.55, 46.0 (CH2NCH2), 76.2 (COH), 77.3
(70), 99 (20), 98 (100), 71 (11), 70 (18), 57 (50), 56 (25), 55 (51), 44 (CH3CH), 125.5, 126.8, 127.85, 145.2 (4 ϫ ArC), 154.7 (CO2). Ϫ
(20), 43 (36). Ϫ C12H23NO3 (229.32): calcd. C 62.85, H 10.11, N
6.11; found C 62.53, H 9.86, N 5.98. Second diastereomer: IR
GC-LRMS: m/z (%) ϭ 246 (Mϩ Ϫ OH, 0.2), 143 (47), 121 (42),
115 (13), 114 (99), 99 (20), 98 (90), 77 (24), 72 (12), 70 (45), 56 (57),
55 (95), 44 (20), 43 (100), 42 (24), 41 (29). Ϫ C15H21NO3 (263.34):
(KBr): ν˜ ϭ 3486 (OH), 1678 (CϭO), 1180, 1132, 1109 (CO) cmϪ1
.
Ϫ 1H NMR: δ ϭ 0.94 [s, 9 H, (CH3)3C], 1.34 (d, J ϭ 6.4 Hz, 3 H, calcd. C 68.42, H 8.04, N 5.32; found C 68.75, H 8.22, N 5.26.
CH3CH), 1.80Ϫ1.95 (m, 4 H, CH2CH2CH2N), 2.12 (br s, 1 H,
N-[(Deuterocyclohexyl)methyloxycarbonyl]pyrrolidine (2c, E ؍
D):
OH), 3.23Ϫ3.45 (m, 5 H, CH2NCH2, CHOH), 5.10 (qd, J ϭ 6.4,
oil, Rf ϭ 0.63 (hexane/ethyl acetate, 1:1). Ϫ IR (film): ν˜ ϭ 1703
1.2 Hz, 1H, CH3CH). Ϫ 13C NMR: δ ϭ 19.5 (CH3CH), 24.75,
24.8 (CH2CH2CH2N), 26.25 [(CH3)3C], 35.0 [(CH3)3C], 45.5, 45.6
1
(CϭO), 1132, 1115, 1099 (CO) cmϪ1. Ϫ H NMR: δ ϭ 0.80Ϫ2.00
[m, 15 H, 11 H cyclohexyl ring, CH2CH2CH2N], 3.32Ϫ3.42 (m, 4
(CH2NCH2), 69.75 (CH3CH), 81.15 (CHOH), 153.8 (CO2). Ϫ GC-
H, CH2NCH2), 3.89 (d, J ϭ 6.4 Hz, 1 H, CHD). Ϫ 13C NMR:
LRMS: m/z (%) ϭ 172 [Mϩ Ϫ (CH3)3C, 16], 116 (15), 114 (37), 98
δ ϭ 24.9, 25.7 (3 C), 26.45 (5 ϫ CH2 cyclohexyl ring), 29.65 (2 C,
CH2CH2CH2N), 37.4 (CHCH2), 45.65, 46.0 (CH2NCH2), 69.75 (t,
(175), 70 (26), 57 (100), 56 (21), 55 (47), 44 (40), 43 (56).
J ϭ 22 Hz, 1 C, CHD), 155.35 (CO2). Ϫ GC-LRMS: m/z (%) ϭ
212 (Mϩ, 0.1), 116, (90), 98 (12), 70 (23), 68 (13), 67 (16), 56 (58),
55 (100), 54 (12).
N-[(2-Ethyl-2-hydroxy-1-methyl)butyloxycarbonyl]pyrrolidine
(2bd): white solid (m.p. 85Ϫ86°C, hexane), Rf ϭ 0.40 (hexane/ethyl
acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ 3475 (OH), 1675 (CϭO), 1131, 1100
(CO) cmϪ1. Ϫ 1H NMR: δ ϭ 0.91 (t, J ϭ 7.5 Hz, 6 H,
2 ϫ CH3CH2), 1.23 (d, J ϭ 6.4 Hz, 3 H, CH3CH), 1.35Ϫ1.68 (m,
4 H, 2 ϫ CH3CH2), 1.80Ϫ1.95 (m, 4 H, CH2CH2CH2N), 1.98 (s,
1 H, OH), 3.30Ϫ3.45 (m, 4 H, CH2NCH2), 4.84 (q, J ϭ 6.4 Hz, 1
H, CH). Ϫ 13C NMR: δ ϭ 7.45, 7.5 (2 ϫ CH3CH2), 14.95
N-[(1-Cyclohexyl-2-ethyl-2-hydroxy)butyloxycarbonyl]pyrrolidine
(2cd): white solid (m.p. 96Ϫ98°C, hexane), Rf ϭ 0.49 (hexane/ethyl
acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ 3462 (OH), 1676 (CϭO), 1130, 1127,
1115 (CO) cmϪ1. Ϫ 1H NMR: δ ϭ 0.88, 0.90 (2 t, J ϭ 7.5, 7.5
Hz, 6 H, 2 ϫ CH3), 1.05Ϫ2.10 (m, 20 H, 11 H cyclohexyl ring,
(CH3CH), 24.85,
25.65
(CH2CH2CH2N), 26.65, 28.1
2 ϫ CH2CH3, CH2CH2CH2N, OH), 3.35- 3.50 (m,
4 H,
(2 ϫ CH3CH2), 45.75, 46.2 (CH2NCH2), 75.1 (CH), 75.8 (COH),
154.85 (CO2). Ϫ GC-LRMS: m/z (%) ϭ 200 (Mϩ Ϫ CH3CH2, 4),
143 (19), 116 (16), 114 (10), 98 (70), 71 (14), 70 (23), 57 (27), 56
(28), 55 (50), 45 (29), 44 (12), 43 (36). Ϫ C12H23NO3 (229.32):
calcd. C 62.85, H 10.11, N 6.11; found C 63.26, H 10.34, N 6.04.
CH2NCH2), 4.64 (d, J ϭ 2.4 Hz, 1 H, CHO). Ϫ 13C NMR: δ ϭ
7.65 (2 C, 2 ϫ CH3), 24.85, 25.65 (CH2CH2CH2N), 26.2, 26.3, 26.6,
26.85, 27.7, 28.8, 32.25 (5 ϫ CH2 cyclohexyl ring, 2 ϫ CH2CH3),
38.45 (CHCH2), 45.7, 46.25 (CH2NCH2), 76.95 (COH), 80.95
(CHO), 155.2 (CO2). Ϫ GC-LRMS: m/z (%) ϭ 268 (Mϩ
Ϫ
CH3CH2, 1), 211 (11), 116 (63), 115 (21), 114 (100), 98 (55), 71
(16), 70 (14), 57 (24), 56 (18), 55 (58), 45 (14), 43 (18). Ϫ
C17H31NO3 (297.44): calcd. C 68.65, H 10.51, N 4.71; found C
68.30, H 10.57, N 4.55.
N-[1-(1Ј-Hydroxycyclohexyl)ethyloxycarbonyl]pyrrolidine
(2be):
white solid (m.p. 72Ϫ74°C, hexane), Rf ϭ 0.38 (hexane/ethyl acet-
ate, 1:1). Ϫ IR (KBr): ν˜ ϭ 3448 (OH), 1681 (CϭO), 1129, 1104
(CO) cmϪ1. Ϫ 1H NMR: δ ϭ 1.23 (d, J ϭ 6.1 Hz, 3 H, CH3),
1.16Ϫ1.78 (m, 11 H, 5 ϫ CH2 cyclohexyl ring, OH), 1.82Ϫ1.94 (m,
4 H, CH2CH2CH2N), 3.30Ϫ3.45 (m, 4 H, CH2NCH2), 4.71 (q, J ϭ
6.1 Hz, 1 H, CH). Ϫ 13C NMR: δ ϭ 14.4 (CH3), 21.25, 21.4, 25.7,
N-[Cyclohexyl-(1Ј-hydroxycyclohexyl)methyloxycarbonyl]-
pyrrolidine (2ce): white solid (m.p. 113Ϫ115°C, hexane), Rf ϭ 0.51
(hexane/ethyl acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ 3505 (OH), 1682 (Cϭ
1
O), 1177, 1134, 1107 (CO) cmϪ1. Ϫ H NMR: δ ϭ 1.02Ϫ2.05 (m,
32.5,
34.05 (5 ϫ CH2
cyclohexyl
ring), 24.8,
25.55
(CH2CH2CH2N), 45.6, 46.05 (CH2NCH2), 72.6 (COH), 76.8 (CH),
154.7 (CO2). Ϫ GC-LRMS: m/z (%) ϭ 212 (Mϩ Ϫ CH3CH2, 0.1),
143 (22), 115 (11), 114 (100), 99 (15), 98 (52), 81 (17), 71 (26), 70
(41), 69 (10), 57 (12), 56 (42), 55 (83), 53 (11), 45 (25), 44 (18), 43
(52), 42 (26), 41 (56). Ϫ C13H23NO3 (241.33): calcd. C 64.70, H
9.61, N 5.80; found C 64.67, H 9.79, N 5.72.
26 H, 10 ϫ CH2 cyclohexyl ring, CH2CH2CH2N, CHCHO, OH),
3.30- 3.50 (m, 4 H, CH2NCH2), 4.53 (d, J ϭ 3.0 Hz, 1 H,
CHCHO). Ϫ 13C NMR: δ ϭ 21.5 (2 C), 24.85, 25.7 (2 C), 26.2,
26.3, 26.55, 27.55, 32.3, 33.25, 35.5 (12 C, CH2CH2CH2N,
10 ϫ CH2 cyclohexyl rings), 38.4 (CHCHO), 45.65, 46.25
(CH2NCH2), 73.8 (COH), 82.85 (CHCHO), 155.2 (CO2). Ϫ GC-
LRMS: m/z (%) ϭ 211 [Mϩ Ϫ (CH2)5CO, 20], 116 (63), 115 (27),
115 (27), 114 (100), 99 (18), 98 (51), 71 (20), 70 (17), 56 (20), 55
(62).
N-[(2-Hydroxy-1-methyl-2-phenyl)propyloxycarbonyl]pyrrolidine
(2bf), First diastereomer: white solid (m.p. 123Ϫ125°C, hexane),
Rf ϭ 0.40 (hexane/ethyl acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ 3436 (OH),
1667 (CϭO), 1198, 1095 (CO) cmϪ1. Ϫ 1H NMR: δ ϭ 1.04 (d, J ϭ
N-[(1-Cyclohexyl-2-hydroxy-2-phenyl)propyloxycarbonyl]-
6.4 Hz, 3 H, CH3CH), 1.58 (s, 3 H, CH3C), 1.80Ϫ1.93 (m, 4 H, pyrrolidine (2cf), First diastereomer: white solid (m.p. 160Ϫ162°C,
CH2CH2CH2N), 2.62 (s,
CH2NCH2), 5.05 (q, J ϭ 6.4 Hz, 1 H, CH), 7.15Ϫ7.47 (m, 5 H,
ArH). δ ϭ 15.1 (CH3CH), 24.9, 25.65 NMR: δ ϭ 0.97Ϫ1.93 [m, 16 H, 11 H cyclohexyl ring,
13C NMR:
1
H, OH), 3.30Ϫ3.45 (m,
4
H, hexane), Rf ϭ 0.42 (hexane/ethyl acetate, 1:1). Ϫ IR (KBr): ν˜ ϭ
3443, 3129 (OH), 1685 (CϭO), 1128, 1108, 1067 (CO) cmϪ1. Ϫ 1H
Ϫ
(CH2CH2CH2N), 27.55 (CH3C), 45.75, 46.25 (CH2NCH2), 76.0 CH2CH2CH2N, OH], 1.51 (s, 3 H, CH3), 3.40Ϫ3.55 (m, 4H,
(COH), 77.4 (CH3CH), 125.35, 126.8, 127.95, 144.2 (4 ϫ ArC), CH2NCH2), 4.91 (d, J ϭ 3.3 Hz, 1 H, CHO), 7.24Ϫ7.51 (m, 5 H,
154.7 (CO2). Ϫ GC-LRMS: m/z (%) ϭ 246 (Mϩ Ϫ OH, 0.1), 143
ArH). Ϫ 13C NMR: δ ϭ 24.9, 25.75 (CH2CH2CH2N), 26.1 (2 C),
(37), 121 (28), 115 (10), 114 (88), 99 (14), 98 (72), 77 (18), 71 (38), 26.3, 27.65, 31.95 (5 ϫ CH2 cyclohexyl ring), 29.4 (CH3), 38.45
70 (33), 56 (44), 55 (77), 44 (15), 43 (100), 42 (14), 41 (23). Ϫ (CHCH2), 45.8, 46.4 (CH2NCH2), 77.1 (COH), 83.25 (CHO),
C15H21NO3 (263.34): calcd. C 68.42, H 8.04, N 5.32; found C
125.15, 126.7, 128.0, 144.55 (4 ϫ ArC), 155.15 (CO2). Ϫ GC-
68.63, H 8.15, N 5.28. Second diastereomer: white solid (m.p. LRMS: m/z (%) ϭ 211 (Mϩ Ϫ CH3COPh, 15), 121 (30), 116 (31),
96Ϫ98°C, hexane), Rf ϭ 0.36 (hexane/ethyl acetate, 1:1). Ϫ IR 115 (15), 144 (60), 99 (13), 98 (97), 71 (23), 70 (14), 56 (27), 55
(KBr): ν˜ ϭ 3427 (OH), 1678 (CϭO), 1129, 1104 (CO) cmϪ1. Ϫ 1H (76), 43 (100). Ϫ C20H29NO3 (331.46): calcd. C 72.47, H 8.82, N
Eur. J. Org. Chem. 1999, 3005Ϫ3012
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