Xu et al.
(1R,2S,5S,8S)-5-Benzyl-1,5,11,11-tetramethyl-3-oxa-6-
azatricyclo[6.2.1.02,7]undec-6-en-4-one (18b): 356 mg (yield 82%);
2.02-1.73 (m, 3H), 1.59-1.51 (m, 2H), 1.41-1.29 (m, 4H), 1.06
(s, 3H), 0.99 (s, 1H), 0.96 (s, 3H), 0.91-0.87 (m, 3H), 0.82 (s,
3H); 13C NMR δ 177.6, 172.2, 133.6, 118.8, 80.9, 66.5, 53.8, 49.8,
48.1, 42.9, 36.4, 34.6, 26.1, 22.8, 21.3, 20.1, 19.4, 13.8, 9.7; MS
m/z 303 (M+, 51.2), 275 (27.2), 247 (100.0), 216 (62.5), 202 (23.8),
190 (22.7), 164 (22.7), 152 (11.1), 107 (16.7), 83 (24.4), 55 (23.2);
HRMS m/e calcd for C19H29NO2 303.2198, found 303.2199. Anal.
Calcd for C19H29NO2: C, 75.21; H, 9.63; N, 4.62; Found: C, 75.22;
H, 9.74; N, 4.6.
[R]22 -70.7 (c ) 1.27, CHCl3); Rf 0.34 (hexanes/EtOAc ) 2/1);
D
mp 118-120 °C; IR (NaCl, CHCl3) 3032 (ms), 2965 (m), 1743
1
(s), 1701 (m) cm-1; H NMR δ 7.34-7.13 (m, 5H), 4.27 (s, 1H),
3.50-3.47 (d, J ) 13.2 Hz, 1H), 3.13-3.09 (d, J ) 13.2 Hz, 1H),
2.29 (d, J ) 4.4 Hz, 1H), 1.98-1.79 (m, 2H), 1.59 (s, 1H), 1.46
(m, 1H), 1.41-1.34 (s, 3H), 1.33-1.29 (m, 1H), 0.96 (s, 3H), 0.84
(s, 3H), 0.21 (s, 3H); 13C NMR δ 176.6, 173.0, 136.9, 131.3, 127.6,
126.4, 80.5, 63.7, 53.8, 49.6, 48.1, 46.7, 34.5, 23.8, 21.2, 19.3, 19.1,
9.7; MS m/z 311 (M+, 43.8), 296 (2.2), 267 (47.1), 252 (30.4),
220 (34.6), 192 (22.4), 176 (100.0), 148 (22.3), 117 (11.2), 91
(55.7), 83 (15.8), 55 (12.0); HRMS m/e calcd for C20H25NO2 M+
311.1886, found M+ 311.1896. Anal. Calcd for C20H25NO2: C,
77.14; H, 8.09; N, 4.50. Found: C, 77.21; H, 8.15; N, 4.60.
(1R,2S,5S,8S)-5-Allyl-5-benzyl-1,11,11-trimethyl-3-oxa-6-
azatricyclo[6.2.1.02,7]undec-6-en-4-one (18c): 354 mg (yield 75%);
(1R,2S,5R,8S)-5-Allyl-1,5,11,11-tetramethyl-3-oxa-6-azatricyclo-
[6.2.1.02,7]undec-6-en-4-one (18g): 340 mg (yield 93%); [R]22
D
-45.1 (c ) 0.41, CHCl3); Rf 0.33 (hexanes/EtOAc ) 2/1); mp 76-
77 °C; 1H NMR NMR δ 5.80-5.71 (m, 1H), 5.18-5.12 (m, 2H),
4.46 (s, 1H), 2.54-2.49 (ddd, J ) 14.0, 7.6, 0.8 Hz, H), 2.41-
2.36 (dd, J ) 13.6, 7.6 Hz, H), 2.40 (d, J ) 4.4, 1H), 2.04-1.82
(m, 2H), 1.62-1.52 (m, 4H), 1.42-1.35 (m, 1H), 1.07 (s, 3H),
0.96 (s, 3H), 0.84 (s, 3H); 13C NMR δ 178.2, 172.9, 131.6, 119.8,
81.6, 62.8, 53.8, 49.8, 48.1, 41.9, 34.5, 26.5, 21.4, 19.8, 19.3, 9.7;
MS m/z 261 (M+, 9.4), 232 (9.3), 217 (90.5), 202 (76.3), 176
(100.0), 174 (41.7), 148 (36.1), 107 (20.0), 83 (41.5), 55 (35.0),
53 (21.7); HRMS m/e calcd for C16H23NO2 261.1722, found
261.1728.
[R]22 -12.0 (c ) 1.39, CHCl3); Rf 0.49 (hexanes/EtOAc ) 2/1);
D
1H NMR δ 7.29-7.11 (m, 5H), 5.89-5.76 (m, 1H), 5.22-5.17
(m, 2H), 4.25 (s, 1H), 3.48 (d, J ) 12.8 Hz, 1H), 3.09 (d, J ) 12.8
Hz), 2.67 (dd, J ) 13.6, 7.2 Hz, 1H), 2.44 (dd, J ) 13.6, 7.6 Hz,
1H), 2.27 (d, J ) 4.8 Hz, 1H), 1.97-1.89 (m, 1H), 1.83-1.72 (m,
1H), 1.54-1.46 (m, 1H), 1.30-1.21 (m, 1H), 0.90 (s, 3H), 0.80
(s, 3H), 0.05 (s, 3H); 13C NMR δ 177.2, 172.1, 136.5, 131.7, 131.3,
127.6, 126.3, 120.1, 81.2, 70.0, 53.8, 49.3, 47.9, 45.7, 43.1, 34.6,
21.5, 19.1, 18.7, 9.4; MS m/z 337 (M+, 22.6), 293 (85.8), 278 (38.7),
252 (26.5), 250 (22.2), 202 (78.3), 174 (12.2), 160 (15.0), 128
(12.6), 91 (100.0), 83 (16.0), 55 (20.4); HRMS m/e calcd for C22H27-
NO2 M+ 337.2042, found M+ 337.2050. Anal. Calcd for C22H27-
NO2: C, 78.30; H, 8.06; N, 4.15. Found: C, 78.26; H, 8.12; N,
4.30.
(1S,2R,5S,8R)-5-Benzyl-5,8,11,11-tetramethyl-3-oxa-6-
azatricyclo[6.2.1.02,7]undec-6-en-4-one (19a): 327 mg (yield 75%);
[R]22 +61.7 (c ) 1.16, CHCl3); Rf 0.56 (hexanes/EtOAc ) 2/1);
D
IR (NaCl, CHCl3) 3061 (s), 3028 (m), 1741 (s), 1695 (m) cm-1
;
1HNMR δ 7.28-7.26 (m, 3H), 7.12-7.09 (m, 2H), 3.34-3.31 (d,
J ) 13.2 Hz, 1H), 2.96-2.92 (d, J ) 13.2 Hz, 1H), 2.40 (s, 1H),
1.81-1.72 (m, 5H), 1.62-1.58 (m, 1H), 1.42-1.34 (m, 1H), 1.04
(s, 3H), 0.84 (s, 3H), 0.69 (s, 3H), 0.66-0.62 (m, 1H); 13C NMR
δ 179.6, 174.2, 136.2, 130.3, 128.5, 127.2, 79.5, 65.0, 52.5, 48.0,
47.3, 45.8, 29.6, 28.9, 28.8, 19.9, 19.1, 10.2; MS m/z 311 (M+,
0.8), 283 (2.4), 267 (100.0), 239 (72.3), 224 (18.3), 192 (29.6),
176 (61.4), 148 (48.1), 117 (11.9), 91 (54.8), 83 (93.1), 69 (17.6);
HRMS m/e calcd for C20H25NO2 M+ 311.1895, found M+ 311.1885.
Anal. Calcd for C20H25NO2: C, 77.14; H, 8.09; N, 4.50. Found:
C, 77.15; H, 8.14; N, 4.51.
(1R,2S,8S)-5,5-Dibenzyl-1,11,11-trimethyl-3-oxa-6-azatricyclo-
[6.2.1.02,7]undec-6-en-4-one (18d). 400 mg (yield 74%); [R]22
D
-41.9 (c ) 1.03, CHCl3); mp 146-147 °C; IR (NaCl, CHCl3) 2960
1
(ms), 2928 (m), 1738 (s), 1705 (m) cm-1; H NMR δ 7.29-7.26
(m, 6H), 7.20-7.11 (m, 4H), 3.68 (d, J ) 12.8 Hz, 1H), 3.54 (d,
J ) 12.8 Hz, 1H), 3.18 (d, J ) 12.8 Hz, 1H), 3.02 (d, J ) 12.8
Hz, 1H), 2.16 (d, J ) 4.8 Hz, 1H), 1.87 (s, 1H), 1.77-1.69 (m,
1H), 1.50-1.42 (m, 1H), 1.31-1.24 (m, 1H), 0.67 (s, 3H), 0.60
(s, 3H), 0.48-0.42 (m, 1H), -0.18 (s, 3H); 13C NMR δ 178.5,
173.0, 136.4, 135.9, 131.4, 130.7, 128.6, 127.9, 127.4, 126.6, 81.0,
69.6, 54.0, 48.5, 48.1, 47.8, 46.1, 34.6, 21.1, 19.0, 18.5, 9.2; MS
m/z 387 (M+, 14.6), 343 (56.1), 328 (36.4), 296 (12.3), 252 (100.0),
224 (16.1), 186 (5.1), 160 (2.6), 115 (7.2), 91 (64.6), 83 (10.1), 55
(6.7); HRMS m/e calcd for C26H29NO2 M+ 387.2205, found M+
387.2199.
(1S,2R,5R,8R)-5-Benzyl-5,8,11,11-tetramethyl-3-oxa-6-
azatricyclo[6.2.1.02,7]undec-6-en-4-one (19b). 383 mg (yield 88%);
[R]22 +48.2 (c ) 1.30, CHCl3), Rf 0.46 (hexanes/EtOAc ) 2/1);
D
1
mp 100-101 °C; H NMR δ 7.36-7.12 (m, 5H), 4.43 (s, 1H),
3.48 (d, J ) 12.8 Hz, 1H), 3.13 (d, J ) 12.8 Hz, 1H), 2.04 (d, J )
4.8 Hz, 1H), 2.00-1.94 (m, 1H), 1.72-1.65 (m, 1H), 1.56-1.49
(m, 1H), 1.46 (s, 3H), 1.32-1.26 (m, 1H), 0.98 (s, 3H), 0.82 (s,
3H), 0.09 (s, 3H); 13C NMR δ 177.8, 173.2, 136.9, 78.5, 63.6, 52.9,
48.2, 47.7, 46.7, 28.9, 25.8, 23.6, 20.0, 18.5, 10.0; MS m/z 311
(M+, 21.9), 283 (6.9), 267 (100.0), 252 (59.2), 239 (76.2), 224
(17.0), 192 (35.7), 176 (54.9), 148 (41.2), 117 (16.7), 91 (86.3),
77 (11.4), 69 (17.9); HRMS m/e calcd for C20H25NO2 M+ 311.1895,
found M+ 311.1890. Anal. Calcd for C20H25NO2: C, 77.14; H, 8.09;
N, 4.50. Found: C, 77.10; H, 8.24; N, 4.48.
(1R,2S,5R,8S)-5-Allyl-5-benzyl-1,11,11-trimethyl-3-oxa-6-
azatricyclo[6.2.1.02,7]undec-6-en-4-one (18e): 368 mg (yield 78%);
[R]22D -15.3 (c ) 2.13, CHCl3); Rf 0.26 (hexanes/EtOAc ) 10/1);
IR (NaCl, CHCl3) 3074 (s), 2961 (m), 1741 (s), 1702 (m) cm-1
;
1H NMR δ 7.29-7.27 (m, 3H), 7.15-7.13 (m, 2H), 5.75-5.67
(m, 1H), 5.23-5.06 (m, 2H), 3.81-3.35 (d, J ) 13.6 Hz, 1H),
3.05-2.99 (dd, J ) 12.8, 7.6 Hz, 1H), 2.96-2.92 (d, J ) 13.6 Hz,
1H), 2.74-2.69 (dd, J ) 12.8, 6.8 Hz, 1H), 2.32-2.31 (d, J ) 4.8
Hz, 1H), 2.04 (s, 1H), 1.81-1.78 (m, 1H), 1.60-1.56 (m, 1H),
1.37-1.32 (m, 1H), 0.84 (s, 3H), 0.77 (s, 3H), 0.73 (s, 3H), 0.57-
0.50 (m, 1H); 13C NMR δ 179.1, 172.8, 135.8, 133.1, 130.4, 128.5,
127.3, 119.3, 81.0, 68.6, 53.9, 48.7, 47.8, 46.7, 45.3, 34.4, 21.0,
20.1, 19.0, 9.2; MS m/z 337 (M+, 57.9), 281 (18.2), 266 (22.1),
246 (23.6), 202 (52.5), 160 (10.6), 146 (4.2), 107 (10.8), 83 (100.0),
47 (19.8); HRMS m/e calcd for C22H27NO2 M+ 337.2042, found
M+ 337.2034.
(1S,2R,5R,8R)-5-Allyl-5-benzyl-8,11,11-trimethyl-3-oxa-6-
azatricyclo[6.2.1.02,7]undec-6-en-4-one (19c): 401 mg (yield 85%);
[R]22 +32.7 (c ) 1.19, CHCl3); Rf 0.60 (hexanes/EtOAc ) 4/1);
D
mp 62-63 °C; 1H NMR δ 7.29-7.27 (m, 2H), 7.14-7.09 (m, 3H),
5.88-5.76 (m, 1H), 5.17-5.05 (m, 2H), 4.41 (s, 1H), 3.48-3.45
(d, J ) 12.4 Hz, 1H), 3.11-3.08 (d, J ) 12.4 Hz, 1H), 1.96-1.87
(m, 2H), 1.71-1.62 (m, 1H), 1.52-1.44 (m, 1H), 1.25-1.19 (m,
1H), 0.97 (s, 3H), 0.77 (s, 3H), -0.07 (s, 3H); 13C NMR δ 178.4,
172.3, 136.6, 131.9, 131.6, 127.5, 126.4, 120.0, 79.4, 67.1, 53.0,
48.1, 47.6, 45.8, 42.9, 29.3, 26.0, 20.0, 18.2, 10.1; MS m/z 337
(M+, 18.1), 293 (100.0), 265 (33.7), 246 (18.0), 202 (30.7), 174
(19.9), 150 (12.2), 120 (7.7), 91 (47.7), 69 (19.6), 55 (5.4); HRMS
m/e calcd for C22H27NO2 M+ 337.2042, found M+ 337.2040. Anal.
Calcd for C22H27NO2: C, 78.30; H, 8.06; N, 4.15. Found: C, 78.26;
H, 8.08; N, 4.23.
(1R,2S,5S,8S)-5-Allyl-5-butyl-1,11,11-trimethyl-3-oxa-6-
azatricyclo[6.2.1.02,7]undec-6-en-4-one (18f): 340 mg (yield 80%);
[R]22 -12.0 (c ) 1.14, CHCl3); IR (NaCl, CHCl3) 2959 (ms),
D
2875 (m), 1741 (s), 1701 (m) cm-1; H NMR δ 5.80-5.73 (m,
1
1H), 5.21-5.16 (d, J ) 17.2 Hz, 1H), 5.09-5.07 (d, J ) 10.4 Hz,
1H), 4.36 (s, 1H), 2.88-2.83 (ddd, J ) 13.6, 6.8, 0.8 Hz, 1H),
2.66-2.60 (ddd, J ) 13.6, 7.2, 0.8 Hz, 1H), 2.41-2.40 (m, 1H),
(1S,2R,5S,8R)-5-Allyl-5-benzyl-8,11,11-trimethyl-3-oxa-6-
azatricyclo[6.2.1.02,7]undec-6-en-4-one (19d): 425 mg (yield 90%);
[R]22D +35.5 (c ) 1.38, CHCl3); Rf 0.41 (hexanes/EtOAc ) 10/1);
4372 J. Org. Chem., Vol. 71, No. 12, 2006