Asymmetric Synthesis of Chiral Azetidine-2-ones
FULL PAPER
Ϫ
13C NMR (50 MHz, CDCl3): δ ϭ 165.1, 157.2. 138.5, 125.5,
129.4, 127.4, 70.5, 66.1, 60.5, 59.4, 59.1, 18.8, 6.7, 4.9. Ϫ MS; m/z:
Compound 5k: M.p. 89 °C. Ϫ [α]2D0 ϭ ϩ88.6 (c ϭ 2.2, CHCl3). Ϫ
IR (CHCl3): ν˜ ϭ 1761, 1748 cmϪ1. Ϫ 1H NMR (200 MHz, CDCl3):
390 [Mϩ], 361 [Mϩ Ϫ Et], 332, 318. Ϫ C20H30N2O4Si (390.5): calcd. δ ϭ 7.40 (s, 5 H), 5.03 (dd, 1 H, J ϭ 8.5, 9.4 Hz), 4.58 (t, 1 H, J ϭ
C 61.51, H 7.74, N 7.17; found C 61.35, H 7.68, N 6.90.
8.5 Hz), 4.42 (m, 2 H), 4.18 (dq, 1 H, J ϭ 3.1, 6.3 Hz), 3.98 (dd,
1 H, J ϭ 8.5, 9.4 Hz), 1.05 (m, 24 H), 0.85 (s, 9 H), 0.18 (s, 3 H),
0.08 (s, 3 H). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ 171.9, 157.5,
136.0, 129.3, 127.4, 70.4, 67.1, 60.10, 59.7, 58.0, 26.0, 18.6, 18.1,
18.0, 16.9, 12.4, Ϫ5.5, Ϫ5.6. Ϫ MS; m/z: 503 [Mϩ Ϫ iPr], 149. Ϫ
C29H50N2O4Si2 (546.9): calcd. C 63.69, H 9.22, N 5.12; found C
63.90, H 9.27, N 5.10.
Compound 5h (Identified as NH-Azetidinone): M.p. 130 °C. Ϫ [α]
20 ϭ ϩ60.0 (c ϭ 0.8, CHCl3). Ϫ IR (CHCl3): ν˜ ϭ 3421, 1753 cmϪ1
.
D
1
Ϫ H NMR (200 MHz, CDCl3): δ ϭ 7.40 (s, 5 H), 5.85 (s, 1 H),
4.92 (dd, 1 H, J ϭ 7.1, 8.8 Hz), 4.68 (t, 1 H, J ϭ 8.8 Hz), 4.20 (dd,
1 H, J ϭ 7.1, 8.8 Hz), 4.04 (d, 1 H, J ϭ 2.6 Hz), 3.98 (dd, 1 H,
J ϭ 2.6, 5.3 Hz), 3.55 (m, 1 H), 0.95 (d, 3 H, J ϭ 6.2 Hz), 0.85 (t,
9 H, J ϭ 7.1 Hz), 0.42 (q, 6 H, J ϭ 7.1 Hz). Ϫ MS; m/z: 390 [Mϩ],
361 [Mϩ Ϫ Et], 332, 318.
(4S)-3-{(3S,4R)-1-(tert-Butyldiphenylsilyl)-2-oxo-4-[(S)-1-(triiso-
propylsilyloxy)ethyl]azetidine-3-yl}-4-phenyloxazolidin-2-one
(4j)
and (4S)-3-{(3R,4S)-1-(tert-Butyldiphenylsilyl)-2-oxo-4-[(S)-1-(trii-
sopropylsilyloxy)ethyl]azetidine-3-yl}-4-phenyloxazolidin-2-one (5j):
The title compounds were prepared from the acyl chloride 2-X1
and the imine 1j following the above procedure. Yields: 0.253 g of
4j and 0.176 g of 5j (64% total yield). Diastereomeric ratio 59:41.
(4S)-3-{(3S,4R)-4-[(S)-1-tert-Butoxyethyl]-2-oxo-1-(trimethylsilyl)-
azetidine-3-yl}-4-phenyloxazolidin-2-one (4i) and (4S)-3-{(3R,4S)-4-
[(S)-1-tert-Butoxyethyl]-2-oxo-1-(trimethylsilyl)azetidine-3-yl}-4-
phenyloxazolidin-2-one (5i): The title compounds were prepared
from the acyl chloride 2-X1 and the imine 1i following the above
procedure. Yields: 0.123 g of 4i and 0.045 g of 5i (63% total yield).
Diastereomeric ratio 73:27.
Compound 4j: M.p. 127 °C. Ϫ [α]2D0 ϭ ϩ74.8 (c ϭ 0.9, CHCl3). Ϫ
IR (CHCl3): ν˜ ϭ 2971, 1752 cmϪ1. Ϫ 1H NMR (200 MHz, CDCl3):
δ ϭ 7.5 (m, 4 H), 7.3 (m, 11 H), 5.15 (d, 1 H, J ϭ 3.1 Hz), 4.90
(dd, 1 H, J ϭ 6.6, 8.8 Hz), 4.67 (t, 1 H, J ϭ 8.7 Hz), 4.10 (dd, 1
H, J ϭ 6.6, 8.6 Hz), 3.36 (d, 1 H, J ϭ 3.1 Hz), 3.00 (q, 1 H, J ϭ
6.5 Hz), 1.12 (s, 9 H), 0.78 (s, 21 H), 0.68 (d, 3 H, J ϭ 6.5 Hz). Ϫ
13C NMR (50 MHz, CDCl3): δ ϭ 171.4, 157.3, 138.3, 136.1, 135.8,
131.7, 131.2, 130.1, 129.9, 129.3, 129.1, 127.8, 127.7, 127.2, 70.8,
66.3, 62.4, 59.8, 55.3, 27.7, 21.5, 19.7, 18.1, 18.0, 13.2. Ϫ MS; m/z:
628 [Mϩ Ϫ iPr], 346, 294. Ϫ C39H54N2O4Si2 (671.0): calcd. C 69.81,
H 8.11, N 4.17; found C 70.09, H 8.15, N 4.20.
Compound 4i (Identified as NH-Azetidinone): M.p. 180 °C. [α]2D0
ϭ
ϩ66.1 (c ϭ 0.6, CHCl3). Ϫ IR (CHCl3): ν˜ ϭ 3425, 1760 cmϪ1. Ϫ
1H NMR (200 MHz, CDCl3): δ ϭ 7.40 (s, 5 H), 5.66 (s, 1 H), 4.98
(dd, 1 H, J ϭ 6.3, 8.8 Hz), 4.84 (d, 1 H, J ϭ 2.4 Hz), 4.69 (t, 1 H,
J ϭ 8.8 Hz), 4.22 (dd, 1 H, J ϭ 6.3, 8.8 Hz), 3.60 (dq, 1 H, J ϭ
3.2, 6.3 Hz), 3.00 (dd, 1 H, J ϭ 3.2, 2.4 Hz), 1.06 (m, 12 H). Ϫ
13C NMR (50 MHz, CDCl3): δ ϭ 165.2, 157.2, 138.5, 129.4, 129.4,
127.3, 73.8, 70.5, 65.0, 61.2, 59.0, 58.7, 28.3, 18.9. Ϫ MS; m/z: 275
[Mϩ Ϫ tBu], 218, 190, 146, 104. Ϫ C18H24N2O4 (332.4): calcd. C
65.04, H 7.28, N 8.43; found C 65.01, H 7.24, N 8.50.
Compound 5j: M.p. 133 °C. Ϫ [α]2D0 ϭ ϩ69.7 (c ϭ 1.6, CHCl3). Ϫ
IR (CHCl3): ν˜ ϭ 2975, 1740 cmϪ1. Ϫ 1H NMR (200 MHz, CDCl3):
δ ϭ 7.65 (m, 4 H), 7.38 (m, 11 H), 5.10 (dd, 1 H, J ϭ 8.5, 9.0 Hz),
4.59 (t, 1 H, J ϭ 8.5 Hz), 4.52 (m, 2 H), 4.00 (dd 1 H, J ϭ 8.5, 9.0
Hz), 3.10 (dq, 1 H, J ϭ 2.9, 6.3 Hz), 1.05 (s, 9 H), 0.85 (d, 21 H),
0.70 (d, 3 H, J ϭ 6.1 Hz). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ
172.4, 157.0, 136.1, 135.9, 135.7, 131.9, 131.3, 130.2, 130.0, 129.3,
128.14, 127.8, 127.3, 70.4, 66.2, 62.0, 59.2, 57.8, 27.7, 19.5, 17.9,
17.9, 16.6, 12.0. Ϫ MS; m/z: 628 [Mϩ Ϫ iPr], 346, 294. Ϫ
C39H54N2O4Si2 (671.0): calcd. C 69.81, H 8.11, N 4.17; found C
69.54, H 8.13, N 4.21.
Compound 5i (Identified as NH-Azetidinone): M.p. 162 °C. Ϫ
[α]2D0 ϭ ϩ89.0 (c ϭ 0.8, CHCl3). Ϫ IR (CHCl3): ν˜ ϭ 3435, 1760
1
cmϪ1. Ϫ H NMR (200 MHz, CDCl3): δ ϭ 7.38 (s, 5 H), 5.82 (s,
1 H), 4.92 (dd, 1 H, J ϭ 7.6, 8.8 Hz), 4.67 (t, 1 H, J ϭ 8.8 Hz),
4.20 (dd, 1 H, J ϭ 7.6, 8.8 Hz), 4.12 (d, 1 H, J ϭ 2.7 Hz), 3.96
(dd, 1 H, J ϭ 2.7, 6.4 Hz), 3.40 (m, 1 H), 1.00 (s, 9 H), 0.93 (d, 3
H, J ϭ 6.2 Hz). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ 165.1, 157.2,
136.9, 129.7, 129.4, 127.7, 73.9, 70.4, 68.0, 62.0, 61.5, 57.9, 28.6,
19.6. Ϫ MS; m/z: 274 [Mϩ Ϫ tBu], 218, 190, 146, 104. Ϫ
C18H24N2O4 (332.4): calcd. C 65.04, H 7.28, N 8.43; found C 64.76,
H 7.24, N 8.39.
(4S)-3-{(3S,4R)-2-Oxo-4-[(S)-1-(triisopropylsilyloxy)ethyl]-1-(tri-
isopropylsilyl)azetidine-3-yl}-4-phenyloxazolidin-2-one (4l) and (4S)-
3-{(3R,4S)-2-Oxo-4-[(S)-1-(triisopropylsilyloxy)ethyl]-1-(triisoprop-
ylsilyl)azetidine-3-yl}-4-phenyloxazolidin-2-one (5l): The title com-
pounds were prepared from the acyl chloride 2-X1 and the imine
1l following the above procedure. Yields: 0.142 g of 4l and 0.116 g
of 5l (44% total yield). Diastereomeric ratio 55:45.
(4S)-3-{(3S,4R)-1-(tert-Butyldimethylsilyl)-2-oxo-4-[(S)-1-(triiso-
propylsilyloxy)ethyl]azetidine-3-yl}-4-phenyloxazolidin-2-one (4k)
and (4S)-3-{(3R,4S)-1-(tert-Butyldimethylsilyl)-2-oxo-4-[(S)-1-(tri-
isopropylsilyloxy)ethyl]azetidine-3-yl}-4-phenyloxazolidin-2-one
(5k): The title compounds were prepared from the acyl chloride 2-
X1 and the imine 1k following the above procedure. Yields: 0.188 g
of 4k and 0.105 g of 5k (54% total yield). Diastereomeric ratio
64:36.
Compound 4l: M.p. 119 °C. Ϫ [α]2D0 ϭ ϩ56.5 (c ϭ 0.9, CHCl3). Ϫ
IR (CHCl3): ν˜ ϭ 1748, 1735 cmϪ1. Ϫ 1H NMR (200 MHz, CDCl3):
δ ϭ 7.35 (s, 5 H), 5.05 (d, 1 H, J ϭ 3.1 Hz), 4.92 (dd, 1 H, J ϭ
6.3, 8.5 Hz) 4.66 (t, 1 H, J ϭ 8.5 Hz) 4.18 (dd, 1 H, J ϭ 1.0, 6.4
Hz), 4.06 (dd, 1 H, J ϭ 6.3, 8.5 Hz), 3.54 (dd, 1 H, J ϭ 1.0, 3.1
Hz), 1.20 (d, 3 H, J ϭ 6.4 Hz), 1.05 (m, 42 H). Ϫ 13C NMR
(50 MHz, CDCl3): δ ϭ 171.0, 157.5, 138.6, 129.3, 129.2, 126.9,
70.9, 67.4, 62.1, 59.4, 21.2, 18.3, 18.2, 13.3, 12.2. Ϫ MS; m/z: 545
[Mϩ Ϫ iPr], 346, 294. Ϫ C32H56N2O4Si2 (588.9): calcd. C 65.26, H
9.58, N 4.76; found C 65.51, H 9.53, N 4.79.
Compound 4k: M.p. 130 °C. Ϫ [α]2D0 ϭ ϩ58.2 (c ϭ 2.1, CHCl3). Ϫ
IR (CHCl3): ν˜ ϭ1750, 1741 cmϪ1. Ϫ 1H NMR (200 MHz, CDCl3):
δ ϭ 7.35 (s, 5 H), 4.97 (d, 1 H, J ϭ 3.1 Hz), 4.93 (dd, 1 H, J ϭ
6.7, 8.8 Hz), 4.65 (t, 1 H, J ϭ 8.8 Hz), 4.14 (m, 1 H), 4.08 (dd, 1
H, J ϭ 6.7, 8.8 Hz), 3.68 (dd, 1 H, J ϭ 1.2, 3.1 Hz), 1.18 (d, 3 H,
J ϭ 6.3 Hz), 0.98 (s, 21 H), 0.84 (s, 9 H), 0.18 (s, 3 H), 0.07 (s, 3
H). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ 170.4, 157.4, 138.5, 129.4,
129.3, 127.1, 70.9, 66.8, 62.3, 59.7, 59.3, 26.1, 20.6, 18.9, 18.3, 13.0,
Compound 5l: M.p. 85 °C. [α]2D0 ϭ ϩ87.7 (c ϭ 1.2, CHCl3). Ϫ IR
1
Ϫ5.48. Ϫ MS; m/z: 503 [Mϩ Ϫ iPr], 328, 149. Ϫ C29H50N2O4Si2 (CHCl3): ν˜ ϭ 1760, 1740 cmϪ1. Ϫ H NMR (200 MHz, CDCl3):
(546.9): calcd. C 63.69, H 9.22, N 5.12; found C 63.40, H 9.17, δ ϭ 7.40 (s, 5 H), 5.06 (dd, 1 H, J ϭ 8.5, 9.4 Hz), 4.63 (t, 1 H, J ϭ
N 5.14.
3.1 Hz), 4.58 (t, 1 H, J ϭ 8.5 Hz), 4.28 (d, 1 H, J ϭ 3.3 Hz), 4.20
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