Eight-Membered-Ring Lactams
FULL PAPER
NMR (CDCl3, 125 MHz): δ = 14.15 (CH3), 24.40 (CH2), 25.33 for compound 4aa a mixture of ester 1b (200 mg, 594 µmol), amine
(CH2), 25.98 (CH2), 26.02 (CH2), 29.52 (CH2), 30.08 (CH2), 31.60 2e (803 mg, 5.94 mmol, 10 equiv.), and Bi(NO3)3·5H2O (30 mg,
(CH2), 34.09 (CH2), 43.78 (CH), 55.84 (CH), 60.94 (CH2), 126.33 60 µmol, 0.1 equiv.) in THF (2 mL) was stirred for 3 d at 70 °C.
(2 CH), 127.04 (CH), 128.43 (2 CH), 128.63 (CH), 138.52 (C), Chromatography on basic Al2O3 [PE/EA, 3:1, Rf(SiO2) = 0.13] gave
139.78 (C), 173.64 (C), 173.70 (C) ppm. IR (ATR): ν = 2931 (m),
compound 4be (31 mg, 79 µmol, 13%) as a yellowish oil. 1H NMR
(CDCl3, 300 MHz): δ = 1.26–1.40 (m, 1 H), 1.64–1.80 (m, 1 H),
1.91–2.03 (m, 1 H), 2.37–2.57 (m, 2 H), 3.58 (part A of an AB
system, J = 13.8 Hz, 1 H), 3.66 (s, 3 H), 3.72–3.81 (m, 2 H), 5.01
(s, 2 H), 5.40 (part B of an AB system, J = 13.8 Hz, 1 H), 5.98 (d,
J = 9.4 Hz, 1 H), 6.67–6.70 (m, 2 H), 7.10–7.14 (m, 2 H), 7.25–
7.43 (m, 10 H) ppm. 13C{1H} NMR (CDCl3, 75 MHz): δ = 24.22
(CH2), 29.44 (CH2), 33.55 (CH2), 43.20 (CH), 47.32 (CH2), 55.09
(CH3), 66.40 (CH2), 113.59 (2 CH), 125.08 (CH), 126.44 (2 CH),
127.85 (2 CH), 128.22 (CH), 128.57 (2 CH), 128.92 (CH), 128.96
(2 CH), 129.49 (C), 130.37 (C), 130.71 (2 CH), 135.63 (C), 139.49
˜
2856 (w), 1731 (vs), 1645 (vs), 1445 (s), 1366 (s), 1176 (s), 1027 (m),
881 (m), 698 (s) cm–1. MS (EI, 70 eV), m/z (%): 355 (13) [M+], 326
(8), 282 (18), 273 (100), 227 (9), 200 (39), 172 (14), 157 (11), 104
(23). C22H29NO3 (355.48): calcd. C 74.33, H 8.22, N 3.94; found C
74.08, H 8.61, N 3.69.
Benzyl 1-Benzyl-8-oxo-2-phenyl-1,4,5,6,7,8-hexahydroazocine-4-car-
boxylate (4bc): According to the procedure given for compound
4aa a mixture of ester 1b (200 mg, 594 µmol), amine 2c (319 mg,
2.97 mmol, 5 equiv.), and Bi(NO3)3·5H2O (60 mg, 120 µmol,
0.2 equiv.) in THF (2 mL) was stirred for 2 d at 70 °C. Chromatog-
raphy on basic Al2O3 [PE/EA, 3:1, Rf(SiO2) = 0.26] gave compound
4bc (182 mg, 427 µmol, 72%) as a yellowish oil. 1H NMR (CDCl3,
500 MHz): δ = 1.29–1.38 (m, 1 H), 1.63 (dq, J = 13.5 Hz, J =
5.9 Hz, 1 H), 1.94–2.02 (m, 2 H), 2.38 (t, J = 10.3 Hz, 1 H), 2.46
(t, J = 12.0 Hz, 1 H), 2.53–2.57 (m, 1 H), 3.61 (part A of an AB
system, J = 13.8 Hz, 1 H), 4.94 (part A of an AB system, J =
12.3 Hz, 1 H), 5.04 (part B of an AB system, J = 12.3 Hz, 1 H),
5.51 (part B of an AB system, J = 13.8 Hz, 1 H), 5.97 (d, J =
9.4 Hz, 1 H), 7.04–7.10 (m, 3 H), 7.16–7.17 (m, 2 H), 7.26–7.27 (m,
3 H), 7.35–7.42 (m, 7 H) ppm. 13C{1H} NMR (CDCl3, 125 MHz):
δ = 24.22 (CH2), 29.47 (CH2), 33.52 (CH2), 43.21 (CH), 47.87
(CH2), 66.40 (CH2), 125.14 (CH), 126.45 (2 CH), 127.44 (CH),
128.15 (2 CH), 128.22 (2 CH), 128.29 (CH), 128.51 (2 CH), 128.99
(2 CH), 129.05 (CH), 129.42 (2 CH), 135.58 (C), 135.76 (C), 136.18
(C), 158.95 (C), 173.38 (C), 173.52 (C) ppm. IR (ATR): ν = 2935
˜
(m), 1733 (s), 1650 (s), 1511 (vs), 1445 (m), 1396 (m), 1301 (s), 1244
(s), 1173 (s), 1031 (m), 915 (w), 821 (w), 734 (m), 697 (s) cm–1. MS
(EI, 70 eV), m/z (%): 455 (13) [M+], 427 (2), 121 (100) [C8H9O+],
91 (6). C29H29NO4 (455.55): calcd. C 76.46, H 6.42, N 3.07; found
C 76.45, H 6.61, N 3.23.
2-(Methylthio)ethyl 1-Benzyl-8-oxo-2-phenyl-1,4,5,6,7,8-hexahy-
droazocine-4-carboxylate (4cc): According to the procedure given
for compound 4aa a mixture of ester 1c (200 mg, 624 µmol), amine
2c (669 mg, 6.24 mmol, 10 equiv.), and Bi(NO3)3·5H2O (15 mg,
30 µmol, 0.05 equiv.) in THF (1.5 mL) was stirred for 2 d at 70 °C.
Chromatography on basic Al2O3 [PE/EA, 2:1, Rf(SiO2) = 0.23] gave
compound 4cc (56 mg, 140 µmol, 23%) as a yellowish oil. 1H NMR
(CDCl3, 500 MHz): δ = 1.26–1.40 (m, 1 H), 1.58–1.82 (m, 1 H),
1.94–2.04 (m, 2 H), 2.14 (s, 3 H), 2.34 (t, J = 10.2 Hz, 1 H), 2.42–
2.55 (m, 2 H), 2.59–2.64 (m, 2 H), 3.62 (part A of an AB system,
J = 13.7 Hz, 1 H), 4.08–4.14 (m, 2 H), 5.48 (part B of an AB
system, J = 13.7 Hz, 1 H), 5.96 (d, J = 9.5 Hz, 1 H), 7.21–7.43 (m,
10 H) ppm. 13C{1H} NMR (CDCl3, 125 MHz): δ = 15.72 (CH3),
24.25 (CH2), 29.44 (CH2), 32.44 (CH2), 33.53 (CH2), 43.20 (CH),
47.86 (CH2), 62.90 (CH2), 125.12 (CH), 126.46 (2 CH), 127.41
(CH), 128.26 (2 CH), 129.00 (2 CH), 129.07 (CH), 129.57 (2 CH),
135.56 (C), 136.31 (C), 139.38 (C), 173.26 (C), 173.56 (C) ppm. IR
(C), 139.43 (C), 173.30 (C), 173.54 (C) ppm. IR (ATR): ν = 3032
˜
(w), 2938 (m), 2863 (w), 1723 (s), 1651 (s), 1496 (s), 1447 (m), 1397
(s), 1282 (w), 1171 (m), 1077 (m), 760 (s), 699 (s) cm–1. MS (EI,
70 eV), m/z (%): 425 (36) [M+], 396 (8), 334 (10), 306 (26), 262
(9), 91 (100). HRMS (EI, 70 eV): calcd. 425.1991 (for C28H27NO3),
found 425.1991 [M+]. C28H27NO3 (425.52): calcd. C 79.03, H 6.40,
N 3.29; found C 78.58, H 6.24, N 3.28.
Benzyl 1-Allyl-8-oxo-2-phenyl-1,4,5,6,7,8-hexahydroazocine-4-car-
boxylate (4bd): According to the procedure given for compound
4aa a mixture of ester 1b (200 mg, 594 µmol), amine 2d (339 mg,
5.94 mmol, 10 equiv.), and Bi(NO3)3·5H2O (30 mg, 60 µmol,
0.1 equiv.) in THF (1 mL) was stirred for 4 d at 70 °C. Chromatog-
raphy on basic Al2O3 [PE/EA, 2:1, Rf(SiO2) = 0.28] gave compound
(ATR): ν = 3029 (w), 2936 (m), 2861 (w), 1731 (vs), 1650 (vs), 1493
˜
(vs), 1445 (s), 1396 (s), 1305 (m), 1172 (s), 1001 (m), 930 (w), 759
(vs), 699 (vs), 631 (s) cm–1. MS (EI, 70 eV), m/z (%): 409 (7) [M+],
335 (15), 318 (21), 290 (13), 91 (100). HRMS (EI, 70 eV): calcd.
409.1712 (for C24H27NO3S), found 409.1712 [M+].
1
4bd (86 mg, 230 µmol, 39%) as a yellowish oil. H NMR (CDCl3,
2-(Methylthio)ethyl 1-Allyl-8-oxo-2-phenyl-1,4,5,6,7,8-hexahy-
droazocine-4-carboxylate (4cd): According to the procedure given
for compound 4aa a mixture of ester 1c (200 mg, 624 µmol), amine
2d (356 mg, 6.24 mmol, 10 equiv.), and Bi(NO3)3·5H2O (30 mg,
60 µmol, 0.1 equiv.) in THF (1.5 mL) was stirred for 2 d at 70 °C.
Chromatography on basic Al2O3 [PE/EA, 2:1, Rf(SiO2) = 0.25] gave
compound 4cd (106 mg, 295 µmol, 47 %) as a yellowish oil. 1H
NMR (CDCl3, 300 MHz): δ = 1.39–1.54 (m, 1 H), 1.73–1.89 (m, 2
H), 1.98–2.03 (m, 1 H), 2.17 (s, 3 H), 2.41–2.53 (m, 2 H), 2.73–2.78
(m, 2 H), 3.00 (t, J = 9.7 Hz, 1 H), 3.25 (dd, J = 7.9 Hz, J =
14.5 Hz, 1 H), 4.29–4.34 (m, 2 H), 4.73 (dd, J = 5.8 Hz, J =
14.2 Hz, 1 H), 5.03 (dd, J = 17.1 Hz, J = 10.0 Hz, 2 H), 5.78 (dddd,
J = 17.0 Hz, J = 10.1 Hz, J = 7.9 Hz, J = 6.1 Hz, 1 H), 6.06 (d, J
= 9.4 Hz, 1 H), 7.38 (s, 5 H) ppm. 13C{1H} NMR (CDCl3,
75 MHz): δ = 15.78 (CH3), 24.15 (CH2), 29.67 (CH2), 32.67 (CH2),
33.49 (CH2), 43.73 (CH), 47.54 (CH2), 63.29 (CH2), 119.19 (CH2),
124.41 (CH), 126.36 (2 CH), 128.85 (2 CH), 129.01 (CH), 131.74
(CH), 135.59 (C), 139.94 (C), 173.56 (C), 173.64 (C) ppm. IR
300 MHz): δ = 1.39–1.53 (m, 1 H), 1.72–1.88 (m, 1 H), 1.96–2.06
(m, 1 H), 2.17 (dd, J = 5.1 Hz, J = 13.9 Hz, 1 H), 2.41–2.57 (m, 2
H), 3.05 (t, J = 10.3 Hz, 1 H), 3.23 (dd, J = 8.1 Hz, J = 14.2 Hz,
1 H), 4.73 (dd, J = 5.7 Hz, J = 14.1 Hz, 1 H), 4.93–5.01 (m, 2 H),
5.18 (s, 2 H), 5.77 (dddd, J = 5.8 Hz, J = 8.0 Hz, J = 10.1 Hz, J =
16.9 Hz, 1 H), 6.05 (d, J = 9.5 Hz, 1 H), 7.32–7.41 (m, 10 H) ppm.
13C{1H} NMR (CDCl3, 75 MHz): δ = 24.11 (CH2), 29.47 (CH2),
33.48 (CH2), 43.74 (CH), 47.49 (CH2), 66.65 (CH2), 119.23 (CH2),
124.47 (CH), 126.35 (2 CH), 127.91 (2 CH), 128.30 (CH), 128.59
(2 CH), 128.86 (2 CH), 129.02 (CH), 131.68 (CH), 135.56 (C),
135.58 (C), 139.95 (C), 173.54 (C), 173.67 (C) ppm. IR (ATR): ν
˜
= 3032 (w), 2931 (m), 2861 (w), 1733 (s), 1650 (s), 1445 (s), 1394
(s), 1307 (m), 1258 (m), 1171 (s), 1151 (s), 1080 (m), 996 (m), 923
(m) cm–1. MS (EI, 70 eV), m/z (%): 375 (80) [M+], 346 (15), 306
(31), 240 (35), 212 (31), 157 (21), 144 (33), 91 (100), 41 (30).
C24H25NO3 (375.47): calcd. C 76.77, H 6.71, N 3.73; found C
76.43, H 6.97, N 4.02.
Benzyl 1-(4-Methoxybenzyl)-8-oxo-2-phenyl-1,4,5,6,7,8-hexahy-
(ATR): ν = 3029 (w), 2936 (m), 2861 (w), 1731 (vs), 1650 (vs), 1493
˜
droazocine-4-carboxylate (4be): According to the procedure given
(s), 1445 (s), 1396 (s), 1305 (m), 1172 (s), 1074 (m), 1001 (w), 877
Eur. J. Org. Chem. 2007, 3227–3238
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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