The Journal of Organic Chemistry
ARTICLE
2934 (ms), 1735 (s), 1685 (m) cm-1; 1H NMR (600 MHz, CDCl3) δ
7.29 (d, J = 8.4 Hz, 2 H, ArH), 7.05 (d, J = 8.4 Hz, 2 H, ArH), 3.40 (d,
J = 13.2 Hz, 1 H, C3-CH2), 2.98 (d, J = 13.2 Hz, 1 H, C3-CH2), 2.42
(dd, J = 13.2, 7.8 Hz, 1 H, C5-H2), 2.08 (dd, J = 16.2, 8.4 Hz, 1 H,
C7-H2), 1.61 (s, 3 H, C7a-CH3), 1.60 (dd, J = 13.2, 9.0 Hz, 1 H,
C5-H2), 1.31 (s, 3 H, C3-CH3), 1.28 (dd, J = 16.2, 8.4 Hz, 1 H,
C7-H2), 0.97 (s, 3 H, C6-CH3), 0.95 (s, 3 H, C6-CH3), 0.44 (dd,
J = 16.8, 9.0 Hz, 1 H, C5a-H), 0.05 (dd, J = 16.8, 8.4 Hz, 1 H,
C6a-H); 13C NMR (150 MHz, CDCl3) δ 173.5 (CdO), 170.5
(CdN), 135.6 (ArC), 132.2 (ArC), 130.6 (ArC), 120.4 (ArC), 81.8
(C7a), 62.6 (C3), 48.3 (C3-CH2), 34.9 (C7), 30.0 (C5), 27.7
(C3-CH3), 27.5 (C6-CH3), 26.6 (C7a-CH3), 25.7 (C5a), 20.5
(C6), 17.4 (C6a), 14.2 (C6-CH3); MS m/z 389 (Mþ, 5.52), 347
(33.8), 345 (33.6), 20 (29.5), 176 (100.0), 169 (26.7), 135 (32.1),
123 (36.6), 115 (26.4), 107 (51.3), 91 (40.4), 77 (21.8); HRMS m/z
calcd for C20H24BrNO2 Mþ 389.0990, found Mþ 389.0981. Anal.
Calcd for C20H24BrNO2: C, 61.54; H, 6.20; N, 3.59. Found: C,
61.50; H, 6.12; N, 3.17.
tert-Butyl 3-{[3S,5aR,6aS,7aS)-2,3,5,5a,6,6a,7,7a-octahydro-3,6,6,-
7a-tetramethyl-2-oxobicyclo[4.1.0]hept-1(6)-eno[3,4-b][1,4]oxazin-
3-yl]methyl}-1H-indole-1-carboxylate (17g). Yield: 387 mg (86%).
White solid. Mp = 126-129 °C; [R]2D3 = -172.6° (c 0.53, CHCl3); IR
(KBr, CHCl3) 3054 (m), 2934 (ms), 1732 (s), 1685 (m), 1367 (s), 1158
(s) cm-1; 1H NMR (600 MHz, CDCl3) δ 7.98 (d, J = 6.0 Hz, 1 H, ArH),
7.69 (d, J = 7.8 Hz, 1 H ArH), 7.38 (s, 1 H, CdCHN), 7.23-7.18 (m, 2
H, ArH), 3.48 (d, J = 13.8 Hz, 1 H, C3-CH2), 3.20 (d, J = 13.8 Hz, 1 H,
C3-CH2), 2.31 (dd, J = 13.2 Hz, 7.8 Hz, 1 H, C5-H2), 2.07 (dd, J =
16.8, 8.4 Hz, 1 H, C7-H2), 1.67 (s, 3 H, C7a-CH3), 1.61 [s, 9 H,
OC(CH3)3], 1.52 (dd, J = 13.2, 9.0 Hz, 1 H, C5-H2), 1.30 (s, 3 H,
C3-CH3), 1.24 (dd, J = 16.8, 8.4 Hz, 1 H, C7-H2), 0.90 (s, 3 H,
C6-CH3), 0.78 (s, 3 H, C6-CH3), -0.04 (s, 1 H, C5a-H), -0.19 (s, 1
H, C6a-H); 13C NMR (150 MHz, CDCl3) δ 173.9 (CdO), 170.5
(CdN), 149.6 (CdO), 134.9 (ArC), 131.3 (ArC), 124.6 (CdCHN),
123.9 (ArC), 122.1 (ArC), 120.5 (ArC), 116.0 (CdCHN), 114.6
(ArC), 83.3 [OC(CH3)3], 81.9 (C7a), 63.2 (C3), 38.6 (C3-CH2),
35.0 (C5), 30.0 (C7), 28.1 [OC(CH3)3], 27.8 (C3-CH3), 27.3
(C6-CH3), 26.5 (C7a-CH3), 24.7 (C5a), 20.3 (C6), 17.2 (C6a), 14.2
(C6-CH3); MS m/z 450 (Mþ, 4.47), 221 (16.5), 174 (28.5), 130
(100.0), 57 (28.7); HRMS m/z calcd for C27H34N2O4 Mþ 450.2519,
found Mþ 450.2526. Anal. Calcd for C27H34N2O4: C, 71.97; H, 7.61; N,
6.22. Found: C, 72.19; H, 7.60; N, 5.99.
(3S,5aR,6aS,7aS)-5,5a,6,6a,7,7a-Hexahydro-3,6,6,7a-tetramethyl-
3-[(naphthalen-1-yl)methyl]bicyclo[4.1.0]hept-1(6)-eno[3,4-b][1,4]-
oxazin-2(3H)-one (17e). Yield: 314 mg (87%). White solid. Mp =
126-129 °C; [R]2D3 = -197.4° (c 0.70, CHCl3); IR (KBr, CHCl3)
1
3061 (m), 2935 (ms), 1735 (s), 1687 (m) cm-1; H NMR (600
MHz, CDCl3) δ 8.36 (d, J = 8.4 Hz, 1 H, ArH), 7.71 (d, J = 7.8 Hz, 1
H, ArH), 7.64 (d, J = 7.8 Hz, 1 H, ArH), 7.50-7.32 (m, 4 H, ArH),
3.85 (d, J = 13.2 Hz, 1 H, C3-CH2), 3.64 (d, J = 13.2 Hz, 1 H,
C3-CH2), 2.03 (dd, J = 13.2, 7.8 Hz, 1 H, C5-H2), 1.88 (dd, J =
16.2, 8.4 Hz, 1 H, C7-H2), 1.76 (s, 3 H, C7a-CH3), 1.33 (dd, J =
13.2, 9.0 Hz, 1 H, C5-H2), 1.23 (s, 3 H, C3-CH3), 1.10 (dd, J = 16.2,
8.4 Hz, 1 H, C7-H2), 0.79 (s, 3 H, C6-CH3), 0.63 (s, 3 H,
C6-CH3), -0.54 (dd, J = 17.4, 9.0 Hz, 1 H, C6a-H), -1.12 (dd,
J = 16.8, 9.0 Hz, 1 H, C5a-H); 13C NMR (150 MHz, CDCl3) δ 173.8
(CdO), 169.4 (CdN), 133.7 (ArC), 133.3 (ArC), 133.2 (ArC),
128.2 (ArC), 127.9 (ArC), 127.2 (ArC), 126.5 (ArC), 125.3 (ArC),
125.3 (ArC), 124.8 (ArC), 81.9 (C7a), 64.2 (C3), 44.7 (C3-CH2),
34.8 (C7), 29.7 (C5), 28.1 (C3-CH3), 27.2 (C6-CH3), 26.7
(C7a-CH3), 24.5 (C6a), 20.0 (C6), 16.9 (C5a), 14.1 (C6-CH3);
MS m/z 361 (Mþ, 22.8), 176 (24.3), 141 (100.0), 107 (10.2); HRMS
m/z calcd for C24H27NO2 Mþ 361.2042, found Mþ 361.2035. Anal.
Calcd for C24H27NO2: C, 79.74; H, 7.53; N, 3.87. Found: C, 79.40;
H, 7.40; N, 3.16.
(3S,5aR,6aS,7aS)-3-Cinnamyl-5,5a,6,6a,7,7a-hexahydro-3,6,6,7a-
tetramethylbicyclo[4.1.0]hept-1(6)-eno[3,4-b][1,4]oxazin-2(3H)-one
(17h). Yield: 304 mg (90%). Colorless oil. [R]2D3 = -187.1° (c 0.76,
CHCl3); IR (KBr, CHCl3) 3027 (m), 2935 (ms), 1737 (s), 1685 (m)
1
cm-1; H NMR (600 MHz, CDCl3) δ 7.23-7.10 (m, 5 H, ArH),
6.42 (d, J = 15.6 Hz, 1 H, CH2CHdCHPh), 6.01-5.95 (m, 1 H,
CH2CHdCHPh), 2.95 (dd, J = 13.2, 6.6 Hz, 1 H, C3-CH2), 2.64
(dd, J = 12.6, 8.4 Hz, 1 H, C3-CH2), 2.51 (dd, J = 13.2, 7.2 Hz, 1 H,
C5-H2), 2.26 (dd, J = 16.8, 8.4 Hz, 1 H, C7-H2), 1.69 (dd, J = 13.2,
9.0 Hz, 1 H, C5-H2), 1.55 (s, 3 H, C3-CH3), 1.38 (dd, J = 16.8, 8.4
Hz, 1 H, C7-H2), 1.35 (s, 3 H, C7a-CH3), 0.99 (s, 3 H, C6-CH3),
0.74 (s, 3 H, C6-CH3), 0.72 (dd, J = 16.8, 9.0 Hz, 1 H, C5a-H), 0.43
(dd, J = 16.8, 8.4 Hz, 1 H, C6a-H);13C NMR (150 MHz, CDCl3) δ
173.9 (CdO), 170.9 (CdN), 137.2 (ArC), 134.0 (CH2CH=CHPh),
128.3 (ArC), 127.1 (ArC), 125.9 (ArC), 124.4 (CH2CHdCHPh),
82.0 (C7a), 62.3 (C3), 46.5 (C3-CH2), 35.1 (C7), 30.3 (C5), 27.8
(C7a-CH3), 27.3 (C6-CH3), 26.6 (C5a), 26.1 (C3-CH3), 20.8
(C6), 17.6 (C6a), 14.4 (C6-CH3); MS m/z 337 (Mþ, 23.2), 176
(35.4), 117 (100.0), 91 (17.4); HRMS m/z calcd for C22H27NO2
Mþ 337.2042, found Mþ 337.2047. Anal. Calcd for C22H27NO2: C,
78.30; H, 8.06; N, 4.15. Found: C, 76.49; H, 8.75; N, 3.89.
(3S,5aR,6aS,7aS)-3-[(Benzo[d][1,3]dioxol-6-yl)methyl]-5,5a,6,6a,-
7,7a-hexahydro-3,6,6,7a-tetramethylbicyclo[4.1.0]hept-1(6)-eno-
[3,4-b][1,4]oxazin-2(3H)-one (17f). Yield: 320 mg (90%). Color-
less oil. [R]2D3 = -217.5° (c 0.77, CHCl3); IR (KBr, CHCl3) 3007
(3S,5aR,6aS,7aS)-3-Allyl-5,5a,6,6a,7,7a-hexahydro-3,6,6,7a-tetra-
methylbicyclo[4.1.0]hept-1(6)-eno[3,4-b][1,4]oxazin-2(3H)-one (17i).
Yield: 240 mg (92%). White solid. Mp = 57-60 °C; [R]2D3 = -175.0° (c
0.60, CHCl3); IR (KBr, CHCl3) 3011 (m), 2937 (ms), 1738 (s), 1684
1
(m), 2934 (ms), 1734 (s), 1686 (m) cm-1; H NMR (600 MHz,
CDCl3) δ 6.72 (s, 1 H, ArH), 6.64 (s, 1 H, ArH), 6.64 (s, 1 H, ArH),
5.84 (d, J = 1.2 Hz, 1 H, OCH2O), 5.80 (d, J = 1.2 Hz, 1 H, OCH2O),
3.32 (d, J = 12.6 Hz, 1 H, C3-CH2), 2.99 (d, J = 12.6 Hz, 1 H,
C3-CH2), 2.50 (dd, J = 13.2, 7.8 Hz, 1 H, C5-H2), 2.11 (dd, J =
16.8, 8.4 Hz, 1 H, C7-H2), 1.65 (dd, J = 13.2, 9.0 Hz, 1 H, C5-H2),
1.59 (s, 3 H, C7a-CH3), 1.32 (dd, J = 16.8, 8.4 Hz, 1 H, C7-H2),
1.32 (s, 3 H, C3-CH3), 1.00 (s, 3 H, C6-CH3), 0.95 (s, 3 H,
C6-CH3), 0.68 (dd, J = 16.8, 9.0 Hz, 1 H, C5a-H), 0.16 (dd, J = 17.4,
8.4 Hz, 1 H, C6a-H); 13C NMR (150 MHz, CDCl3) δ 173.6 (CdO),
170.4 (CdN), 146.5 (ArC), 146.1 (ArC), 130.3 (ArC), 123.7 (ArC),
111.1 (ArC), 107.7 (ArC), 100.6 (OCH2O), 81.8 (C7a), 63.1 (C3),
48.7 (C3-CH2), 35.0 (C7), 30.2 (C5), 27.9 (C6-CH3), 27.7
(C3-CH3), 26.6 (C7-CH3), 25.9 (C5a), 20.7 (C6), 17.6 (C6a),
14.3 (C6-CH3); MS m/z 355 (Mþ, 7.91), 176 (10.5), 135
(100.0); HRMS m/z calcd for C21H25NO4 Mþ 355.1784, found
Mþ 355.1788. Anal. Calcd for C21H25NO4: C, 70.96; H, 7.09; N,
3.94. Found: C, 70.50; H, 7.55; N, 3.40.
(m) cm-1 1H NMR (600 MHz, CDCl3) δ 5.63-5.56 (m, 1 H,
;
CH2CHdCH2), 5.12-5.02 (m, 2 H, CH2CHdCH2), 2.78 (dd, J =
13.2, 7.2 Hz, 1 H, C3-CH2), 2.55 (dd, J = 13.2, 7.2 Hz, 1 H, C5-H2),
2.54 (dd, J = 13.2, 7.8 Hz, 1 H, C3-CH2), 2.37 (dd, J = 16.8, 7.8 Hz, 1 H,
C7-H2), 1.73 (dd, J = 13.2, 9.0 Hz, 1 H, C5-H2), 1.49 (s, 3 H,
C7a-CH3), 1.47 (dd, J = 16.8, 9.0 Hz, 1 H, C7-H2), 1.38 (s, 3 H,
C3-CH3), 1.07 (s, 3 H, C6-CH3), 1.05 (s, 3 H, C6-CH3), 0.94 (dd, J =
16.8, 9.0 Hz, 1 H, C5a-H), 0.74 (dd, J = 17.4, 8.4 Hz, 1 H, C6a-H); 13
C
NMR (150 MHz, CDCl3) δ 173.8 (CdO), 171.0 (CdN), 132.7
(CH2CHdCH2), 119.0 (CH2CH=CH2), 81.6 (C7a), 62.0 (C3), 47.3
(C3-CH2), 35.4 (C7), 30.2 (C5), 27.7 (C6-CH3), 27.7 (C3-CH3),
26.4 (C7a-CH3), 26.2 (C5a), 20.8 (C6), 17.7 (C6a), 14.5 (C6-CH3);
MS m/z 261 (Mþ, 43.6), 217 (38.4), 202 (32.8), 176 (100.0), 174
(30.4), 135 (33.8), 123 (26.0), 110 (37.9), 107 (56.2), 93 (42.1), 91
(32.7), 79 (25.7), 67 (40.8); HRMS m/z calcd for C16H23NO2 Mþ
1629
dx.doi.org/10.1021/jo1022537 |J. Org. Chem. 2011, 76, 1621–1633