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S. M. Husain et al. / Tetrahedron: Asymmetry 20 (2009) 1383–1392
C-6), 47.0 (1C, CH2Ph), 50.5 (1C, C-11), 62.5 (1C, C-2), 69.0 (1C, C-3),
97.4 (1C, C-11a), 125.2, 125.5, 126.2, 127.0, 127.1, 127.2, 127.9,
128.0, 128.2, 128.6, 129.2, 130.1 (19C, Ph-CH), 133.4, 138.2,
138.7, 140.1, 143.1 (5C, Ph-C), 169.5 (1C, C@O). HPLC: purity
99.9%, tR = 25.36 min.
5.10. (3R,6S,11aR)-6-Benzyl-11a-butyl-3-phenyl-2,3,11,11a-
tetrahydro[1,3]oxazolo [2,3-b]-[3]-benzazepin-5(6H)-one 9c
Following the general procedure A, cis-7c (100 mg, 0.30 mmol)
was benzylated to afford 180 mg of crude product, which was puri-
fied by fc (2 cm, EtOAc/cyclohexane 1/9, 15 mL, Rf = 0.56 (EtOAc/
5.7. (3S,6S,11aS)-6-Benzyl-3,11a-diphenyl-2,3,11,11a-
tetrahydro[1,3]oxazolo[2,3-b]-[3]-benzazepin-5(6H)-one ent-8d
cyclohexane 4/6)). Pale yellow viscous oil, yield 116 mg (91%).
20
½
a
ꢂ
¼ þ25:5 (c 0.59, CH2Cl2). FT-IR (ATR, film):
m
(cmꢀ1) = 3027
289
(w, arom C–H), 2962, 2871 (w, aliph C–H), 1658 (s, C@O). MS (EI):
m/z = 425 [M, 4], 368 [MꢀC4H9, 49], 120 [PhCHCH2O, 37], 91[C7H7,
21]. 1H NMR (CDCl3): d (ppm) = 0.90 (t, J = 7.2 Hz, 3H, CH3), 1.28–
1.55 (m, 4H, CH2CH2CH3), 1.77 (ddd, J = 14.0/11.5/4.5 Hz, 1H,
Following the general procedure A, ent-trans-6d (200 mg,
0.56 mmol) was benzylated to afford 310 mg of crude product,
which was purified by fc (2 cm, EtOAc/cyclohexane 1.5/8.5,
15 mL, Rf = 0.40 (EtOAc/cyclohexane 2/8)) and further purified by
CH2CH2CH2CH3),
1.96
(ddd,
J = 14.1/11.6/4.8 Hz,
1H,
recrystallization (CH2Cl2/n-hexane). Colorless solid, mp 131–
CH2CH2CH2CH3), 3.07 (dd, J = 14.0/5.1 Hz, 1H, CH2Ph), 3.46 (s, 2H,
11-H), 3.62 (dd, J = 12.8/7.6 Hz, 1H, 6-H), 3.65 (dd, J = 9.2/2.0 Hz,
1H, 2-H), 4.10 (dd, J = 8.9/5.1 Hz, 1H, CH2Ph), 4.26 (dd, J = 9.1/
7.6 Hz, 1H, 2-H), 4.85 (dd, J = 7.6/2.0 Hz, 1H, 3-H), 6.45 (d,
J = 7.3 Hz, 2H, arom), 6.92 (t, J = 7.6 Hz, 2H, arom), 7.03 (m, 1H,
arom), 7.14–7.38 (m, 9H, arom). 13C NMR (CDCl3): d (ppm) = 14.2
(1C, CH3), 23.0 (1C, CH2CH3), 26.0 (1C, CH2CH2CH3), 32.8 (1C, CH2Ph),
38.8 (1C, CH2CH2CH2CH3), 42.8 (1C, C-11), 49.2 (1C, 6-C), 60.4 (1C, C-
2), 70.5 (1C, C-3), 96.3 (1C, C-11a), 125.3, 125.4, 126.3, 127.1, 127.3,
127.7, 128.4, 128.6, 129.3, 130.5 (14C, Ph-CH), 135.1, 140.1, 140.5,
142.1 (4C, Ph-C), 168.3 (1C, C@O). HPLC: purity99.2%, tR = 25.57 min.
20
133 °C, yield 233 mg (93%). ½
aꢂ
¼ þ45:4 (c 0.38, CH2Cl2). HPLC:
589
purity 99.7%, tR = 25.28 min.
5.8. (3R,6S,11aR)-6-Benzyl-11a-methyl-3-phenyl-2,3,11,11a-
tetrahydro[1,3]oxazolo [2,3-b]-[3]-benzazepin-5(6H)-one (9a)
Following the general procedure A, cis-7a (127 mg, 0.43 mmol)
was benzylated to afford 270 mg of crude product, which was puri-
fied by fc (2 cm, EtOAc/cyclohexane 1.5/8.5, 15 mL, Rf = 0.41
(EtOAc/cyclohexane 1.5/8.5)) and was further purified by recrystal-
lization (CH2Cl2/n-hexane). Colorless solid, mp 207–209 °C yield
20
589
133.4 mg (80%). ½
aꢂ
¼ þ40:3 (c 1.24, CH2Cl2). FT-IR (ATR, film):
5.11. (R)-2-[(1R,4R)-1-Benzyl-4-methyl-2,3,4,5-tetrahydro-1H-
3-benzazepin-3-yl]-2-phenylethanol 12a
m
(cmꢀ1) = 3028 (w, arom C–H), 2922 (w, aliph C–H), 1658 (car-
bonyl C@O). MS (EI): m/z (%) = 383 [M, 7], 368 [MꢀCH3, 5], 120
[PhCHCH2O, 100], 91 [C7H7, 54], 77 [C6H5, 17]. 1H NMR (CDCl3): d
(ppm) = 1.63 (s, 3H, CH3), 3.10 (dd, J = 14.0/5.1 Hz, 1H, CH2Ph),
3.46 (d, J = 15.5 Hz, 1H, 11-H), 3.58 (d, J = 15.5 Hz, 1H, 11-H), 3.64
(dd, J = 14.0/8.9 Hz, 1H, CH2Ph), 3.72 (dd, J = 9.2/1.8 Hz, 1H, 2-H),
4.07 (dd, J = 8.9/5.1 Hz, 1H, 6-H), 4.32 (dd, J = 9.2/7.5 Hz, 1H, 2-H),
4.89 (dd, J = 7.4/1.7 Hz, 1H, 3-H), 6.50 (dd, J = 8.1/1.0 Hz, 2H, arom),
6.94 (t, J = 7.6 Hz, 2H, arom), 7.01–7.06 (m, 1H, arom), 7.15–7.39
(m, 9H, arom). 13C NMR (CDCl3): d (ppm) = 26.5 (1C, CH3), 32.8
(1C, CH2Ph), 45.5 (1C, C-11), 49.2 (1C, C-6), 60.2 (1C, C-3), 70.7
(1C, C-2), 94.3 (1C, C-11a), 125.4, 125.6, 126.3, 127.2, 127.3,
127.8 128.4, 128.6, 129.2, 130.4 (14C, Ph-CH), 135.1, 140.1, 140.5,
142.0 (4C, Ph-C), 168.2 (1C, C@O). HPLC: purity 99.9%,
tR = 23.32 min.
Following the general procedure B, 8a (245 mg, 0.64 mmol,
1 equiv) was reduced to give 192 mg of the crude product, which
was purified by fc (2 cm, EtOAc/cyclohexane 1/9, 15 mL, Rf = 0.67
(EtOAc/petroleum ether/NH3 50/49.5/0.5)). Colorless viscous li-
20
589
quid, yield 125 mg (52%). ½
a
ꢂ
¼ ꢀ8:4 (c 1.31, CH2Cl2). FT-IR
(ATR, film):
m
(cmꢀ1) = 3422 (w, OH), 3059, 3025 (w, arom C–H),
2928 (w, aliph C–H). MS (EI): m/z (%) = 372 [MH+, 0.5], 340
[MꢀCH2OH, 100], 91 [C7H7, 78]. 1H NMR (CDCl3): d (ppm) = 0.93
(s, broad, 3H, CH3), 2.49–2.53 (m, 2H, 2-H/5-H), 2.69 (br s, 1H,
OH), 2.93 (dd, J = 13.0/8.6 Hz, 1H, CH2Ph), 3.04 (dd, J = 13.4/
6.4 Hz, 1H, CH2Ph), 3.15–3.27 (m, 3H, 2-H/4-H/5-H), 3.34 (dd,
J = 14.5/7.4 Hz, 1H, 1-H), 3.57 (dd, J = 10.5/4.8 Hz, 1H, CH2OH),
3.77 (t, J = 10.2 Hz, 1H, CH2OH), 3.95 (dd, J = 10.1/4.8 Hz, 1H,
NCHPh), 6.97–7.15 (m, 8H, arom), 7.21–7.36 (m, 6H, arom). 13C
NMR (CDCl3): d (ppm) = 17.7 (1C, CH3), 40.7 (1C, CH2Ph), 41.9
(1C, C-1), 49.0 (1C, C-5), 49.5 (1C, C-4), 52.2 (1C, C-2), 61.1 (1C,
CH2OH), 64.6 (1C, NCHPh), 126.2, 126.3, 126.8, 127.1, 128.5,
128.6, 129.4, 130.7 (14C, Ph-CH), 136.7, 138.1, 140.3, 142.1 (4C,
Ph-C). HPLC: purity 99.9%, tR = 20.85 min.
5.9. (3R,6S,11aR)-6-Benzyl-11a-ethyl-3-phenyl-2,3,11,11-
tetrahydro[1,3]oxazolo[2,3-b]-[3]-benzazepin-5(6H)-one 9b
Following the general procedure A, cis-7b (285 mg, 0.93 mmol)
was benzylated to afford 445 mg of crude product, which was puri-
fied by fc (3 cm, EtOAc/cyclohexane 1/9, 25 mL, Rf = 0.61 (EtOAc/
cyclohexane 4/6)). Colorless viscous liquid, yield 237.6 mg (64%).
5.12. (R)-2-[(1R,4R)-1-Benzyl-4-ethyl-2,3,4,5-tetrahydro-1H-3-
benzazepin-3-yl]-2-phenylethanol 12b
20
½aꢂ
¼ þ36:4 (c 1.19, CH2Cl2). FT-IR (ATR, film):
m
(cmꢀ1) = 3027
589
(w, arom C–H), 2922 (w, aliph C–H), 1654 (s, C@O). MS (EI): m/z
(%) = 397 [M, 2], 368 [M-CH2CH3, 100], 120 [PhCHCH2O, 25], 91
[C7H7, 14]. 1H NMR (CDCl3): d (ppm) = 1.07 (t, J = 7.4 Hz, 3H,
CH2CH3), 1.79 (dq, J = 14.6/7.3 Hz, 1H, CH2CH3), 2.04 (dq, J = 14.8/
7.5 Hz, 1H, CH2CH3), 3.08 (dd, J = 14.1/5.1 Hz, 1H, CH2Ph), 3.42 (d,
J = 15.4 Hz, 1H, 11-H), 3.48 (d, J = 15.4 Hz, 1H, 11-H), 3.63 (dd,
J = 13.6/8.3 Hz, 1H, CH2Ph), 3.66 (dd, J = 9.1/2.0 Hz, 1H, 2-H), 4.08
(dd, J = 8.8/5.2 Hz, 1H, 6-H), 4.24 (dd, J = 9.1/7.6 Hz, 1H, 2-H),
4.86 (dd, J = 7.6/1.9 Hz, 1H, 3-H), 6.47 (d, J = 8.4 Hz, 2H, arom),
6.93 (t, J = 7.6 Hz, 2H, arom), 7.04 (ddd, J = 7.2/4.0/1.1 Hz, 1H,
arom), 7.14–7.39 (m, 9H, arom). 13C NMR (CDCl3): d (ppm) = 8.2
(1C, CH2CH3), 31.7 (1C, CH2CH3), 32.8 (1C, C-11), 42.3 (1C, CH2Ph),
49.1 (1C, C-6), 60.3 (1C, C-2), 70.5 (1C, C-3), 96.5 (1C, C-11a), 125.3,
125.4, 126.3, 127.1, 127.3, 127.7, 128.4, 128.6, 129.3, 130.6 (14C,
Ph-CH), 135.0, 140.1, 140.5, 142.1 (4C, Ph-C), 168.3 (1C, C@O).
HPLC: purity 99.8%, tR = 23.03 min.
Following the general procedure B, 8b (150 mg, 0.37 mmol,
1 equiv) was reduced to give 155 mg of the crude product, which
was purified by fc (2 cm, EtOAc/cyclohexane 0.5/9.5, 15 mL,
Rf = 0.45 (EtOAc/cyclohexane 2/8)). Colorless viscous oil, yield
20
589
86.5 mg (59.4%). ½
aꢂ
¼ ꢀ15:1 (c 1.23, CH2Cl2). FT-IR (ATR, film):
m
(cmꢀ1) = 3419 (w, O–H), 3059, 3025 (w, arom C–H), 2929, 2872
(w, aliph C–H). MS (EI): m/z (%) = 354 [MꢀCH2OH, 100], 117
[PhCH@CHN, 8], 91 [C7H7, 19], 77 [C6H5, 40]. 1H NMR (CDCl3): d
(ppm) = 0.80 (t, J = 7.3 Hz, 3H, CH2CH3), 1.11–1.18 (m, 2H, CH2CH3),
2.55–2.60 (m, br, 1H, 5-H), 2.70 (dd, J = 14.8/4.2 Hz, 1H, CH2Ph),
2.88–2.97 (m, 2H, 5-H/2-H), 3.05–3.18 (m, 3H, CH2Ph/2-H/4-H),
3.25–3.32 (m, 1H, 1-H), 3.57 (dd, J = 10.4/4.7 Hz, 1H, CH2OH),
3.79 (t, J = 10.0 Hz, 1H, NCHPh), 3.89 (dd, J = 9.6/4.7 Hz, 1H, CH2OH),
6.99–7.14 (m, 8H, arom), 7.18–7.34 (m, 6H, arom). A signal for the
OH proton could not be detected. 13C NMR (CDCl3): d (ppm) = 11.1