Pedrosa et al.
1H); 2.13 (m, 1H); 3.69 (s, 3H); 3.73 (td, 1H, J1 ) 10.0 Hz, J2
) 4.6 Hz); 4.23 (s, 1H); 5.05 (s, 1H); 5.49 (s, 1H); 6.70 (d, 2H,
J ) 8.8 Hz); 7.03-7.15 (m, 5H); 7.29 (d, 2H, J ) 8.8 Hz). 13C
NMR (δ): 21.1; 22.2; 24.6; 25.0; 31.0; 34.9; 41.4; 44.4; 51.6;
54.8; 71.7; 75.8; 75.9; 87.8; 112.4 (2C); 126.4; 126.9 (4C); 127.3
(2C); 130.4; 139.9; 158.2. IR (film): 3525 (broad); 3065; 3030;
1615; 1585; 765; 735; 700; 650; 620 cm-1. Anal. calcd for C26H33-
NO3: C, 76.62; H, 8.16; N, 3.44. Found: C, 76.71; H, 8.29; N,
3.56.
(1S,2S,2aS,3aR,5R,7aS)-2-(2-Furyl)-1-phenyl-5,8,8-tri-
methyl-1H,3aH-azeto[2,1-b][1,3]benzoxazin-2-ol (11f). Col-
orless solid. Mp: 148-149 °C (from hexane). [R]D25 ) +85.6 (c
) 0.99, CHCl3). 1H NMR (δ): 0.74 (s, 3H); 0.99-1.13 (m, 2H);
1.03 (d, 3H, J ) 6.5 Hz); 1.23 (s, 3H); 1.27 (m, 1H); 1.59-1.65
(m, 3H); 1.80 (m, 1H); 2.10 (m, 1H); 3.70 (td, 1H, J1 ) 10.4
Hz, J2 ) 4.3 Hz); 4.05 (broad, s, 1H); 4.98 (s, 1H); 5.50 (s, 1H);
6.08 (dd, 1H, J1 ) 3.2 Hz, J2 ) 0.6 Hz); 6.17 (dd, 1H, J1 ) 3.2
Hz, J2 ) 1.8 Hz); 7.12-7.27 (m, 6H). 13C NMR (δ): 20.9; 22.2;
24.6; 24.7; 31.0; 34.8; 41.3; 44.5; 51.4; 71.6; 73.3; 74.5; 86.4;
107.4; 109.2; 126.7 (3C); 127.1 (2C); 139.9; 141.6; 151.6. IR
(Nujol): 3380 (broad); 3100; 3070; 3030; 1595; 1585; 1550; 770;
735; 710; 700 cm-1. Anal. calcd for C23H29NO3: C, 75.17; H,
7.95; N, 3.81. Found: C, 75.28; H, 8.09; N, 3.70.
The reaction was quenched by addition of water, and the
product was extracted with EtOAc (4 × 25 mL). The combined
organic layers were washed with water, dried over MgSO4, and
concentrated under vacuum. The residue was redissolved in
THF (10 mL) and slowly added to a suspension of LiAlH4 (0.57
g, 15.0 mmol) and AlCl3 (0.67 g, 5.0 mmol) in THF (35 mL)
cooled to -10 °C. The reaction mixture was stirred at room
temperature for 5 h and then heated at reflux for 2-3 h (TLC).
The mixture was allowed to reach room temperature and was
quenched by an addition of 10% aqueous solution of NaOH (4
mL). The mixture was filtered, the solid was washed with hot
EtOAc, and the organic layer was dried over MgSO4. The
solvent was eliminated under vacuum, and the residue was
chomatographed on silica gel using hexanes/EtOAc 8:1 as
eluent.
(2S,3R)-N-(8-Mentholyl)-3-benzyloxy-2-vinyl-azeti-
dine (16a). Yield 75%. Colorless oil. [R]D25 ) +14.30 (c ) 1.0,
CHCl3). 1H NMR (δ): 0.78-0.98 (m, 3H); 0.89 (d, 3H, J ) 6.5
Hz); 0.94 (s, 3H); 1.00 (s, 3H); 1.08 (m, 1H); 1.39 (m, 1H); 1.53
(m, 1H); 1.63 (m, 1H); 1.90 (m, 1H); 2.96 (dd, 1H, J1 ) 7.1 Hz,
J2 ) 6.1 Hz); 3.45 (dd, 1H, J1 ) 6.1 Hz, J2 ) 5.5 Hz); 3.57 (td,
1H, J1 ) 10.6 Hz, J2 ) 4.1 Hz); 3.77-3.87 (m, 2H); 4.40 (d,
1H, J ) 11.7 Hz); 4.50 (d, 1H, J ) 11.7 Hz); 5.06 (dd, 1H, J1
) 10.2 Hz, J2 ) 1.2 Hz); 5.23 (dd, 1H, J1 ) 17.4 Hz, J2 ) 1.2
Hz); 5.91 (ddd, 1H, J1 ) 17.4 Hz, J2 ) 10.2 Hz, J3 ) 7.6 Hz);
7.24-7.38 (m, 5H); 8.33 (broad, s, 1H). 13C NMR (δ): 18.5; 20.0;
22.0; 25.2; 30.8; 34.8; 44.0; 47.8; 50.6; 59.6; 68.3; 71.2; 72.6;
73.2; 116.3; 127.8 (3C); 128.3 (2C); 137.4; 140.1.IR (film): 3170
(broad); 3085; 3065; 3030; 1640; 790; 735; 700 cm-1. Anal. calcd
for C22H33NO2: C, 76.92; H, 9.68; N, 4.08. Found: C, 77.08;
H, 9.76; N, 3.98.
(1S,2S,2aS,3aR,5R,7aS)-1-(3,4-Dimethoxyphenyl)-2-
phenyl-5,8,8-trimethyl-1H,3aH-azeto[2,1-b][1,3]-
benzoxazin-2-ol (11g). Colorless oil. [R]D25 ) +96.3 (c ) 1.0,
CHCl3). 1H NMR (δ): 0.71 (s, 3H); 0.89-1.08 (m, 2H); 0.97 (d,
3H, J ) 6.6 Hz); 1.22 (s, 3H); 1.25 (m, 1H); 1.50-1.65 (m, 3H);
1.72 (m, 1H); 2.06 (m, 1H); 3.56 (s, 3H); 3.64 (td, 1H, J1
)
10.3 Hz, J2 ) 4.3 Hz); 3.70 (s, 3H); 4.16 (broad, s, 1H); 4.92 (s,
1H); 5.47 (s, 1H); 6.50-6.55 (m, 2H); 6.65 (m, 1H); 7.04-7.15
(m, 3H); 7.30-7.33 (m, 2H). 13C NMR (δ): 21.4; 22.3; 24.8; 25.1;
31.2; 35.0; 41.5; 44.5; 51.8; 55.5 (2C); 71.9; 75.5; 76.4; 87.6;
109.7; 110.7; 119.4; 126.5 (2C); 126.9; 127.3 (2C); 132.7; 138.3;
147.6; 147.8. IR (film): 3535; 3450 (broad); 3065; 3030; 1610;
1590; 770; 735; 700; 650 cm-1. Anal. calcd for C27H35NO4: C,
74.11; H, 8.06; N, 3.20. Found: C, 74.22; H, 8.21; N, 3.33.
(2S, 3R)-N-(8-Mentholyl)-3-benzyloxy-3-phenyl-2-vinyl-
azetidine (16b). Yield 65%. Colorless oil. [R]D25 ) -20.5 (c )
1
0.60, CHCl3). H NMR (δ): 0.62-0.90 (m, 3H); 0.72 (d, 3H, J
) 6.5 Hz); 0.74 (s, 3H); 0.94 (s, 3H); 1.05 (m, 1H); 1.21 (m,
1H); 1.35-1.49 (m, 2H); 1.77 (m, 1H); 3.23 (d, 1H, J ) 8.1 Hz);
3.40 (td, 1H, J1 ) 10.6 Hz, J2 ) 4.1 Hz); 3.78 (d, 1H, J ) 8.1
Hz); 3.93 (d, 1H, J ) 11.4 Hz); 3.98 (d, 1H, J ) 11.4 Hz); 4.03
(d, 1H, J ) 6.8 Hz); 4.64 (m, 1H); 4.85-4.96 (m, 2H); 7.03-
7.28 (m, 10H); 7.87 (broad, s, 1H). 13C NMR (δ): 18.2; 20.4;
22.0; 25.2; 30.8; 34.8; 44.2; 47.9; 52.3; 59.9; 65.6; 71.3; 72.3;
79.7; 117.5; 127.1 (2C); 127.4 (3C); 127.5; 128.3 (2C); 128.5
(2C); 137.4; 138.0; 138.5. IR (film): 3185 (broad); 3065; 3030;
1640; 1605; 1585; 780; 735; 710 cm-1. Anal. calcd for C28H37-
NO2: C, 80.15; H, 8.89; N, 3.34. Found: C, 80.33; H, 9.02; N,
3.48.
(1S,2S,2aS,3aR,5R,7aS)-2-Phenyl-1,5,8,8-tetramethyl-
1H,3aH-azeto[2,1-b][1,3]benzoxazin-2-ol (11h). Colorless
oil. [R]D25 ) -2.50 (c ) 0.4, EtOAc). 1H NMR (δ): 0.65 (d, 3H,
J ) 6.1 Hz); 0.90-1.04 (m, 3H); 0.92 (d, 3H, J ) 6.5 Hz); 0.93
(s, 3H); 1.07 (s, 3H); 1.39-1.48 (m, 2H); 1.58 (m, 1H); 1.67 (m,
1H); 1.92 (m, 1H); 3.51 (td, 1H, J1 ) 10.4 Hz, J2 ) 4.4 Hz);
3.80 (s, 1H); 3.96 (q, 1H, J ) 6.1 Hz); 5.04 (s, 1H); 7.18-7.32
(m, 3H); 7.60-7.63 (m, 2H). 13C NMR (δ): 18.5; 21.1; 22.2; 24.8;
25.2; 31.2; 35.0; 41.5; 44.6; 51.3; 67.6; 71.6; 73.4; 89.1; 125.9
(2C); 126.9; 127.6 (2C); 139.4. IR (film): 3530; 3345 (broad);
3065; 3030; 1725; 1675; 1600; 1580; 765; 700 cm-1. Anal. calcd
for C20H29NO2: C, 76.15; H, 9.27; N, 4.44. Found: C, 76.29;
H, 9.14; N, 4.38.
(2S, 3R)-N-(8-Mentholyl)-3-benzyloxy-3-phenyl-2-(trans-
1-phenyl-but-1-enyl)-azetidine (16c). Yield 78%. Colorless
25
1
oil. [R]D ) +41.7 (c ) 1.0, CHCl3). H NMR (δ): 0.56 (t, 3H,
J ) 7.4 Hz); 0.95-1.22 (m, 3H); 1.00 (d, 3H, J ) 6.4 Hz); 1.08
(s, 3H); 1.18 (s, 3H); 1.34-1.49 (m, 2H); 1.65-1.87 (m, 4H);
2.12 (m, 1H); 3.50 (d, 1H, J ) 8.2 Hz); 3.77 (td, 1H, J1 ) 10.4
Hz, J2 ) 4.1 Hz); 4.01 (d, 1H, J ) 8.2 Hz); 4.24 (d, 1H, J )
11.9 Hz); 4.31 (d, 1H, J ) 11.9 Hz); 4.61 (s, 1H); 5.43 (dd, 1H,
J1 ) 8.4 Hz, J2 ) 6.8 Hz); 7.09-7.50 (m, 15H); 8.19 (broad s,
1H). 13C NMR (δ): 13.5; 17.7; 20.5; 22.0; 22.1; 25.4; 30.8; 34.9;
44.1; 47.8; 51.9; 60.5; 66.1; 72.3; 72.8; 82.0; 126.3; 126.8 (2C);
127.1; 127.3; 127.6; 127.7 (2C); 128.1 (2C); 128.2 (3C); 128.6
(2C); 135.0; 135.5; 137.5; 138.4; 140.2. IR (film): 3180 (broad);
3060; 3030; 1600; 755; 730; 700 cm-1. Anal. calcd for C36H45-
NO2: C, 82.56; H, 8.66; N, 2.67. Found: C, 82.28; H, 8.56; N,
2.80.
(3R,4aR,5aS,6R,7S,11aS)-6,8-Diphenyl-7-ethyl-3,11,11-
trimethyl-2,3,4,4a,6,7,11,11a-octahydro-1 H,5aH-pyrido-
[2,1-b][1,3]benzoxazin-6-ol (15). Colorless solid. Mp: 142-
25
143 °C (from EtOH). [R]D ) +176.87 (c ) 0.8, CHCl3). 1H
NMR (δ): 0.42 (t, 3H, J ) 7.5 Hz); 0.84 (d, 3H, J ) 6.5 Hz);
0.88-1.00 (m, 3H); 1.08 (s, 3H); 1.21-1.33 (m, 3H); 1.37 (s,
3H); 1.59-1.74 (m, 4H); 3.04 (m, 1H); 3.18 (s, 1H); 3.31 (td,
1H, J1 ) 10.5 Hz, J2 ) 4.2 Hz); 4.61 (s, 1H); 6.39 (s, 1H); 7.11-
7.36 (m, 8H); 7.53 (d, 2H, J ) 7,3 Hz). 13C NMR (δ): 13.8;
17.8; 20.2; 21.9; 25.0; 26.1; 30.9; 34.4; 40.6; 46.8; 49.1; 57.0;
74.6; 75.6; 86.1; 117.4; 125.0; 125.6 (2C); 126.3 (3C); 127.6 (3C);
128.0 (2C); 141.9; 144.5. IR (Nujol): 3560 (broad); 3040; 1620;
1590; 760; 700 cm-1. Anal. calcd for C29H37NO2: C, 80.70; H,
8.64; N, 3.25. Found: C, 80.56; H, 8.51; N, 3.23.
(2S, 3R)-N-(8-Mentholyl)-3-benzyloxy-2,3-diphenyl-
azetidine (16d). Yield 72%. Colorless solid. Mp: 64-65 °C
25
1
Synthesis of Amino Alcohols 16a-g. General Method.
To a slurry of NaH (72.0 mg, 3.0 mmol) in THF (15 mL) was
added a solution of the appropriate azetidin-3-ol 11a-g (1.5
mmol) in THF (8 mL). The mixture was stirred for 25 min at
room temperature and then a solution of benzyl bromide (0.27
mL, 2.25 mmol) in THF (4 mL) was added. The stirring was
continued at room temperature for 70-90 h (an additional
reflux for 1 h was necessary for protection of compound 11g).
(from pentane). [R]D ) -12.7 (c ) 1.0, CHCl3). H NMR (δ):
0.72 (s, 3H); 0.79-1.07 (m, 3H); 0.94 (d, 3H, J ) 6.4 Hz); 1.20
(s, 3H); 1.27-1.42 (m, 2H); 1.60-1.70 (m, 2H); 2.04 (m, 1H);
3.50 (d, 1H, J ) 8.4 Hz); 3.65 (td, 1H, J1 ) 10.4 Hz, J2 ) 4.0
Hz); 4.09-4.18 (m, 3H); 4.89 (s, 1H); 6.98-7.35 (m, 15H); 8.38
(s, 1H). 13C NMR (δ): 17.6; 20.4; 22.0; 25.2; 30.6; 34.8; 44.1;
47.8; 51.6; 60.1; 65.9; 72.2; 73.0; 81.2; 126.8; 127.1; 127.3 (4C);
127.6 (3C); 127.8 (3C); 128.1 (3C); 136.4; 138.0; 138.8. IR
1414 J. Org. Chem., Vol. 70, No. 4, 2005