Synthesis of 4,4-Disubstituted â-Lactams
J . Org. Chem., Vol. 61, No. 19, 1996 6503
42 (53). Anal. Calcd (Found) for 9c, C10H19NO: C, 70.96; H,
11.31; N, 8.27 (C, 71.10; H, 11.24; N, 8.15).
homoallylamine 13. Vacuum distillation led also to partial
decomposition of azetidines 10a ,c. However, a purified sample
could be obtained by utilization of a high vacuum distillation
and by trapping of the most volatile fraction in a cold finger.
2,2-Dim eth yl-1-isop r op yla zetid in e (10a ): 1H NMR (270
MHz, CDCl3) δ 0.91 (6H, d, J ) 6.27 Hz), 1.24 (6H, s), 1.77
(2H, t, J ) 6.93 Hz), 2.60 (1H, septet, J ) 6.27 Hz), 3.05 (2H,
t, J ) 6.93 Hz); 13C NMR (67.8 MHz, CDCl3) δ 21.10, 25.44,
31.16, 46.95, 50.10, 62.73; IR (NaCl, cm-1) νmax ) 1460, 1378,
1362, 1332, 1290, 1266, 1222, 1203, 1048; MS (70 eV) m/ z (rel
int) 128 (M+ + 1, 5), 127 (M+, 24), 113 (10), 112 (61), 98 (10),
84 (29), 72 (12), 71 (13), 70 (60), 69 (13), 57 (12), 56 (100), 55
(20), 44 (28), 43 (38), 42 (65). Anal. Calcd (Found) for 10a ,
C8H17N: N, 11.01 (N, 11.19).
1-ter t-Bu t yl-4,4-d iet h yl-2-a zet id in on e (9d ): 1H NMR
(270 MHz, CDCl3) δ 0.97 (6H, t, J ) 7.42 Hz), 1.39 (9H, s),
1.72 and 1.86 (4H, d × d × q, J ) 7.28 Hz, J gem ) 14.51 Hz),
2.50 (2H, s); 13C NMR (67.8 MHz, CDCl3) δ 8.90, 28.30, 30.28,
42.17, 54.70, 64.89, 166.92; IR (NaCl, cm-1) νCdO ) 1735; MS
(70 eV) m/ z (rel int) 183 (M+, 15), 168 (22), 154 (11), 126 (3),
112 (11), 98 (31), 85 (8), 84 (100), 70 (6), 69 (49), 67 (2), 58
(31), 57 (42), 56 (36), 55 (20), 54 (4), 53 (3), 43 (9), 42 (13).
Anal. Calcd (Found) for 9d , C11H21NO: C, 72.08; H, 11.55;
N, 7.64 (C, 71.95; H, 11.51; N, 7.75). Upon preparative gas
chromatographic analysis (235 °C, 30 µL), azetidinone 9d
rearranged partially into â,γ-unsaturated carboxylic amide 12
(E/Z 47/53 determined by capillary GC).
1-ter t-Bu tyl-2-eth yl-2-m eth yla zetid in e (10c): 1H NMR
(270 MHz, CDCl3) δ 0.81 (3H, t, J ) 7.42 Hz), 1.00 (9H, s),
1.23 (3H, s), 1.45-1.58 (2H, m), 1.60-1.72 (1H, m), 1.89-1.97
(1H, m), 3.04-3.09 (1H, m), 3.11-3.23 (1H, m); 13C NMR (67.8
MHz, CDCl3) δ 8.82, 27.58, 28.50, 35.09, 41.35, 52.92, 68.57;
IR (NaCl, cm-1) νmax ) 1450, 1365, 1360, 1235, 1146, 1137,
1100, 1067; MS (70 eV) m/ z (rel int) 156 (M+ + 1, 3), 155 (M+,
16), 140 (38), 126 (20), 112 (4), 98 (6), 84 (19), 83 (10), 70 (100),
58 (27), 57 (26), 55 (24), 42 (21). Anal. Calcd (Found) for 10c,
C10H21N: N, 9.02 (N, 8.85).
4-Ben zyl-1-isop r op yl-4-m et h yl-2-a zet id in on e (9e): 1H
NMR (270 MHz, CDCl3) δ 1.37 (3H, d, J ) 5.94 Hz), 1.38 (3H,
s), 1.41 (3H, d, J ) 6.93 Hz), 2.49 and 2.92 (2H, 2×d, AB, J )
14.51 Hz), 2.97 and 3.00 (2H, 2 × d, AB, J ) 13.53 Hz), 3.50
(1H, septet, J ) 6.43 Hz), 7.1-7.4 (5H, m); 13C NMR (67.8
MHz, CDCl3) δ 21.89, 22.01, 23.58, 44.78, 45.37, 47.98, 59.08,
126.88, 128.50, 129.77, 136.91, 165.77; IR (NaCl, cm-1) νCdO
) 1725; MS (70 eV) m/ z (rel int) 217 (M+, 3), 174 (2), 160 (3),
159 (2), 132 (10), 131 (6), 130 (10), 127 (14), 126 (100), 117
(24), 91 (20), 84 (72), 77 (4), 65 (9), 43 (22), 42 (95). Anal. Calcd
(Found) for 9e, C14H19NO: N, 6.45 (N, 6.57).
1-ter t-Bu tyl-2,2-d ieth yla zetid in e (10d ): 1H NMR (270
MHz, CDCl3) δ 0.89 (3H, t, J ) 7.43 Hz), 0.99 (9H, s), 1.4-1.6
(2H, m), 1.68 (2H, t, J ) 6.93 Hz), 3.11 (2H, t, J ) 6.93 Hz);
13C NMR (67.8 MHz, CDCl3) δ 9.04, 23.23, 27.62, 29.87, 41.53,
52.47, 71.57; IR (NaCl, cm-1) νmax ) 1455, 1350, 1250, 1233;
MS (70 eV) m/ z (rel int) 169 (M+, 12), 154(26), 140(33), 112(4),
86(30), 84(100), 70(20), 58(29), 57(36), 56(19), 55(35), 44(4),
43(4), 42(9). Anal. Calcd (Found) for 10d , C11H23N: N, 8.27
(N, 8.40).
4-Ben zyl-1-ter t-Bu tyl-4-m eth yl-2-a zetid in on e (9f): 1H
NMR (270 MHz, CDCl3) δ 1.48 (9H, s), 1.48 (3H, s), 2.33 and
2.89 (2H, 2 × d, AB, J ) 14.52 Hz), 2.99 and 3.20 (2H, 2 × d,
AB, J ) 13.20), 7.1-7.4 (5H, m); 13C NMR (67.8 MHz, CDCl3)
δ 25.10, 28.95, 46.47, 47.22, 55.26, 60.88, 126.83, 128.46,
129.92, 137.16, 166.45; IR (NaCl, cm-1) νCdO ) 1730; MS (70
eV) m/ z (rel int) 231 (M+, 7), 216 (3), 190 (6), 174 (5), 160 (5),
159 (7), 140 (69), 132 (19), 117 (27), 91 (27), 84 (100), 77 (6),
65 (11), 57 (78), 43 (19), 42 (34). Anal. Calcd (Found) for 9f,
C15H21NO: C, 77.88; H, 9.15; N, 6.05 (C, 77.69; H, 9.04; N,
6.11).
Ack n ow led gm en t. The authors are indebted to the
Belgian National Fund for Scientific Research and the
I.W.T. for financial support.
Red u ction of 1,4,4-Tr isu bstitu ted Azetid in on es 9 to
1,2,2-Tr isu bstitu ted Azetid in es 10. To an ice-cooled solu-
tion of â-lactam 9 (1 mmol) in diethyl ether (2 mL) was added
lithium aluminum hydride (0.08 g, 2 mmol). This solution was
stirred under reflux for 7-16 h after which the reaction
mixture was cooled in an ice bath and the reaction was
quenched by a few drops of water. Filtration over a potassium
carbonate layer and evaporation in vacuo yielded azetidines
10 in a purity of 87-92%. Azetidine 10d was distilled (bp 68-
71 °C/8 mmHg, oil bath 120 °C) but suffered from a consider-
able amount of ring opening, resulting in the formation of
Su p p or tin g In for m a tion Ava ila ble: Full spectroscopic
data (1H NMR, 13C NMR, IR, and MS) and physical data for
the R-chloro ketimines (precursors to cyclopropylamines 5e,f),
compounds 5a-f, 11-13, and 3-benzyl-3-buten-2-one (4 pages).
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J O960296K