DiastereoselectiVe Synthesis of Enantiopure Morpholines
(δ): 11.5 (CH3), 22.0 (CH3), 25.9 (CH2), 27.7 (CH3), 26.1 (CH3),
27.3 (CH3), 31.0 (CH), 34.6 (CH2), 40.9 (CH2), 43.8 (N-CH2),
48.5 (C), 50.0 (CH), 55.9 (C), 74.2 (CH), 80.7 (CH), 82.2 (CH),
87.0 (CH), 127.3 (CH), 127.4 (2CH), 127.7 (2CH), 128.5 (CH),
128.6 (2CH), 128.7 (C), 138.4 (2CH), 139.7 (C). IR (Nujol
dispersion): 3080, 760, 725, 700 cm-1. Anal. Calcd for C29H39-
NO2Se: C, 67.95; H, 7.67; N, 2.73. Found: C, 68.07; H, 7.73; N,
2.80.
J2 ) 1.9 Hz), 4.48 (t, 1H, J ) 1.9 Hz), 7.22-7.30 (m, 3H), 7.48-
7.53 (m, 2H). 13C NMR (δ): 20.9 (CH3), 22.2 (CH3), 25.0 (CH2),
26.2 (CH3), 30.4 (CH2), 31.3 (CH), 34.9 (CH2-SePh), 41.2 (CH2),
43.4 (CH), 45.1 (CH2), 55.8 (C), 70.0 (CH2), 75.8 (CH), 76.1 (CH),
79.7 (CH), 126.9 (CH), 129.0 (2CH), 130.2 (C), 132.6 (2CH). IR
(film): 3040, 3020, 1580, 745, 680, 650 cm-1. Anal. Calcd for
C21H31NO2Se: C, 61.75; H, 7.65; N, 3.43. Found: C, 61.87; H,
7.77; N, 3.54.
(1S,4S,7aS,10R,11aR,12aS)-1-Phenyl-4-phenylselenenyl-3,3,7,7,-
10-pentamethyl-decahydro-3H,7H-[1,4]oxazepino[3,4-b][1,3]-
benzoxazine (7e). Colorless oil. [R]25D ) +48.0 (c ) 1.0, CH2Cl2).
1H NMR (δ): 0.65 (s, 3H), 0.73-1.01 (m, 3H), 0.87 (d, 3H, J )
6.4 Hz), 1.04 (s, 3H), 1.13 (m, 1H), 1.22-1.48 (m, 2H), 1.30 (s,
3H), 1.62 (m, 1H), 1.65 (s, 3H), 1.80 (m, 1H), 3.03 (dd, 1H, J1 )
14.5 Hz, J2 ) 1.6 Hz), 3.31 (td, 1H, J1 ) 10.6 Hz, J2 ) 3.9 Hz),
3.39 (dd, 1H, J1 ) 10.9 Hz, J2 ) 1.6 Hz), 3.52 (dd, 1H, J1 ) 14.5
Hz, J2 ) 10.9 Hz), 4.59 (d, 1H, J ) 7.5 Hz), 4.66 (d, 1H, J ) 7.5
Hz), 7.19-7.32 (m, 6H), 7.48-7.52 (m, 2H), 7.63-7.69 (m, 2H).
13C NMR (δ): 20.9 (CH3), 21.1 (CH3), 22.3 (CH3), 24.9 (CH2),
26.9 (CH3), 30.9 (CH3), 31.2 (CH), 34.9 (CH2), 41.4 (CH2), 44.3
(CH2), 47.1 (CH), 57.0 (C), 59.5 (CH), 74.4 (CH), 75.1 (CH), 78.3
(C), 89.4 (CH), 126.4 (2CH), 126.8 (CH), 127.6 (CH), 127.8 (2CH),
129.0 (2CH), 129.9 (C), 135.1 (2CH), 142.7 (C). IR (film): 3040,
3020, 1610, 740, 690 cm-1. Anal. Calcd for C29H39NO2Se: C,
67.95; H, 7.67; N, 2.73. Found: C, 67.86; H, 7.78; N, 2.70.
(1S,3R,6aS,9R,10aR,11aS)-1-Phenyl-3-(1-methyl-1-phenylse-
lenenylethy)-1,6,6,9-tetramethyl-decahydro-3H,7H-[1,4]oxazino-
(3S,6aS,9R,10aR,11aS)-3-Phenylselenenylmethyl-6,6,9-trimethyl-
decahydro-3H,7H-[1,4]oxazino[3,4-b][1,3]benzoxazine (6g). Col-
orless oil. [R]25D ) +1.7 (c ) 1.0, CH2Cl2). 1H NMR (δ): 0.80-
1.18 (m, 3H), 0.87 (s, 3H), 0.89 (d, 3H, J ) 6.6 Hz), 1.06 (s, 3H),
1.30 (m, 1H), 1.40 (m, 1H), 1.62-1.68 (m, 2H), 1.89 (m, 1H),
2.11 (dd, 1H, J1 ) 11.6 Hz, J2 ) 9.9 Hz), 2.87 (dd, 1H, J1 ) 12.5
Hz, J2 ) 6.4 Hz), 3.01 (dd, 1H, J1 )12.5 Hz, J2 ) 3.7 Hz), 3.03
(dd, 1H, J1 ) 11.6 Hz, J2 ) 2.2 Hz), 3.29 (dd, 1H, J1 ) 10.9 Hz,
J2 ) 8.7 Hz), 3.35 (td, 1H, J1 ) 10.6 Hz, J2 ) 4.2 Hz), 3.73 (dddd,
1H, J1 ) 9.9 Hz, J2 ) 6.4 Hz, J3 ) 3.7 Hz, J4 ) 2.2 Hz), 3.86 (dd,
1H, J1 ) 10.9 Hz, J2 ) 3.7 Hz), 4.06 (dd, 1H, J1 ) 8.7 Hz, J2 )
3.7 Hz), 7.20-7.28 (m, 3H), 7.49-7.54 (m, 2H). 13C NMR (δ):
11.4 (CH3), 22.1 (CH3), 24.9 (CH2), 25.2 (CH3), 30.2 (CH2), 31.0
(CH), 34.5 (CH2), 41.1 (CH2), 47.1 (CH2), 49.9 (CH), 55.3 (C),
69.7 (CH2), 74.4 (CH), 75.8 (CH), 81.2 (CH), 127.1 (CH), 129.0
(2CH), 129.8 (C), 132.9 (2CH). IR (film): 3040, 3050, 1580, 750,
730, 680 cm-1. Anal. Calcd for C21H31NO2Se: C, 61.75; H, 7.65;
N, 3.43. Found: C, 61.64; H, 7.76; N, 3.50.
(3R,6aS,9R,10aR,11aS)-3-(1-Methyl-1-phenylselenenylethy)-
6,6,9-trimethyl-decahydro-3H,7H-[1,4]oxazino[3,4-b][1,3]-
benzoxazine (5h). Colorless oil. [R]25D ) -29.5 (c ) 0.5, CH2Cl2).
1H NMR (δ): 0.78-1.04 (m, 2H), 0.92 (d, 3H, J ) 6.5 Hz), 1.10
(s, 3H), 1.09 (m, 1H), 1.20 (s, 3H), 1.37 (s, 3H), 1.38-1.59 (m,
3H), 1.41 (s, 3H), 1.69 (m, 1H), 1.91 (m, 1H), 2.92 (dd, 1H, J1 )
10.4 Hz, J2 ) 2.3 Hz), 3.04 (t, 1H, J ) 10.4 Hz), 3.40 (dd, 1H, J1
) 10.4 Hz, J2 ) 2.3 Hz), 3.49 (td, 1H, J1 ) 10.4 Hz, J2 ) 4.1 Hz),
3.57 (dd, 1H, J1 ) 11.8 Hz, J2 ) 1.9 Hz), 3.94 (dd, 1H, J1 ) 11.8
Hz, J2 ) 1.0 Hz), 4.50 (dd, 1H, J1 ) 1.9 Hz, J2 ) 1.0 Hz), 7.21-
7.38 (m, 3H), 7.61-7.67 (m, 2H). 13C NMR (δ): 21.5 (CH3), 22.2
(CH3), 25.1 (CH2), 26.0 (CH3), 26.4 (CH3), 26.6 (CH3), 31.3 (CH),
34.9 (CH2), 40.9 (CH2), 41.2 (CH2), 43.1 (CH), 48.8 (C), 55.9 (C),
70.4 (CH2), 76.0 (CH), 79.5 (CH), 82.8 (CH), 127.4 (CH), 128.5
[3,4-b][1,3]benzoxazine (5f). Colorless oil. [R]25 ) -97.2 (c )
D
1.3, CH2Cl2). 1H NMR (δ): 0.85-1.35 (m, 4H), 0.95 (d, 3H, J )
6.4 Hz), 1.06 (s, 3H), 1.32 (s, 3H), 1.35 (s, 3H), 1.36 (s, 3H), 1.38
(s, 3H), 1.44-1.64 (m, 2H), 1.70 (m, 1H), 2.01 (m, 1H), 2.72 (dd,
1H, J1 ) 10.3 Hz, J2 ) 2.3 Hz), 3.17 (t, 1H, J ) 10.3 Hz), 3.42
(dd, 1H, J1 ) 10.3 Hz, J2 ) 2.3 Hz), 3.57 (td, 1H, J1 ) 10.6 Hz,
J2 ) 3.9 Hz), 5.1 (s, 1H), 7.17-7.33 (m, 6H), 7.41-7.45 (m, 2H),
7.58-7.65 (m, 2H). 13C NMR (δ): 21.5 (CH3), 22.4 (CH3), 25.2
(CH2), 26.6 (CH3), 26.8 (2CH3), 29.0 (CH3), 31.5 (CH), 35.1 (CH2),
40.4 (CH2), 41.3 (CH2), 43.5 (CH), 49.4 (C), 56.4 (C), 77.1 (2CH),
77.8 (C), 82.4 (CH), 126.2 (2CH), 126.4 (CH), 128.0 (C), 128.1
(C), 128.2 (2CH), 128.3 (2CH), 132.7 (2CH), 145.3 (C). IR
(film): 3040, 1590, 1440, 1350, 730, 690 cm-1. Anal. Calcd for
C30H41NO2Se: C, 68.42; H, 7.85; N, 2.66. Found: C, 68.51; H,
7.72; N, 2.79.
(3CH), 138.5 (2CH). IR (film): 3040, 1585, 740, 695, 670 cm-1
.
Anal. Calcd for C23H35NO2Se: C, 63.29; H, 8.08; N, 3.21. Found:
C, 63.38; H, 8.21; N, 3.12.
(1S,3S,6aS,9R,10aR,11aS)-1-Phenyl-3-(1-methyl-1-phenylse-
lenenylethy)-1,6,6,9-tetramethyl-decahydro-3H,7H-[1,4]oxazino-
(4S,7aS,10R,11aR,12aS)-3,3,7,7,10-Pentamethyl-4-phenylse-
lenenyl-decahydro-3H,7H-[1,4]oxazepino[3,4-b][1,3]-
benzoxazine (7h). Colorless oil. [R]25D ) +68.9 (c ) 0.6, CH2Cl2).
1H NMR (δ): 0.78 (s, 3H), 0.80-0.95 (m, 2H), 0.89 (d, 3H, J )
6.5 Hz), 1.03 (s, 3H), 1.05 (m, 1H), 1.24 (m, 1H), 1.27 (s, 3H),
1.41 (m, 1H), 1.43 (s, 3H), 1.50 (m, 1H), 1.66 (m, 1H), 1.89 (m,
1H), 2.98 (d, 1H, J ) 13.0 Hz), 3.41 (td, 1H, J1 ) 10.3 Hz, J2 )
4.0 Hz), 3.43 (d, 1H, J ) 9.0 Hz), 3.51 (dd, 1H, J1 ) 13.0 Hz, J2
) 9.0 Hz), 3.68-3.71 (m, 2H), 4.56 (t, 1H, J ) 3.9 Hz), 7.19-
7.26 (m, 3H), 7.56-7.61 (m, 2H). 13C NMR (δ): 19.8 (CH3), 22.2
(CH3), 24.7 (CH3), 25.0 (CH2), 27.0 (CH3), 27.4 (CH3), 31.2 (CH),
34.8 (CH2), 41.3 (CH2), 44.3 (CH2), 46.6 (CH), 56.7 (C), 57.5 (CH),
64.9 (CH2), 75.5 (CH), 77.2 (C), 83.4 (CH), 127.2 (CH), 128.9
(2CH), 130.9 (C), 134.0 (2CH). IR (film): 3040, 1580, 735, 690,
675 cm-1. Anal. Calcd for C23H35NO2Se: C, 63.29; H, 8.08; N,
3.21. Found: C, 63.41; H, 7.97; N, 3.35.
(4R,7aS,10R,11aR,12aS)-3,3,7,7,10-Pentamethyl-4-phenylse-
lenenyl-decahydro-3H,7H-[1,4]oxazepino[3,4-b][1,3]-
benzoxazine (8h). Colorless oil. 1H NMR (δ): 0.68 (s, 3H, CH3),
0.74-0.92 (m, 2H), 0.84 (s, 3H), 0.88 (d, 3H, J ) 6.5 Hz), 0.97
(m, 1H), 1.13 (m, 1H), 1.23 (s, 3H), 1.39 (m, 1H), 1.48 (s, 3H),
1.53-1.64 (m, 2H), 1.87 (m, 1H), 2.83 (dd, 1H, J1 ) 13.8 Hz, J2
) 8.8 Hz), 3.09 (d, 1H, J ) 13.8 Hz), 3.29 (td, 1H, J1 ) 10.6 Hz,
J2 ) 4.2 Hz), 3.56-3.59 (m, 3H), 4.05 (t, 1H, J ) 5.5 Hz), 7.22-
7.29 (m, 3H), 7.56-7.65 (m, 2H). 13C NMR (δ): 12.2 (CH3), 22.0
(CH3), 24.9 (CH2), 25.1 (CH3), 25.3 (CH3), 25.6 (CH3), 30.8 (CH),
[3,4-b][1,3]benzoxazine (6f). Colorless solid. Mp: 184-185 °C
1
(from ethanol). [R]25 ) -8.2 (c ) 0.5, CH2Cl2). H NMR (δ):
D
0.84-1.13 (m, 3H), 0.85 (s, 3H), 0.91 (d, 3H, J ) 6.5 Hz), 1.16
(s, 3H), 1.21-1.38 (m, 2H), 1.41 (s, 3H), 1.44 (s, 3H), 1.56 (s,
3H), 1.58-1.70 (m, 2H), 1.85 (m, 1H), 2.38 (t, 1H, J ) 10.6 Hz),
3.16 (td, 1H, J1 ) 10.4 Hz, J2 ) 4.1 Hz), 3.23 (dd, 1H, J1 ) 10.6
Hz, J2 ) 2.1 Hz), 3.76 (s, 1H), 3.89 (dd, 1H, J1 ) 10.6 Hz, J2 )
2.1 Hz), 7.20-7.39 (6H, m), 7.59-7.68 (m, 4H). 13C NMR (δ):
11.4 (CH3), 18.2 (CH3), 22.2 (CH3), 24.9 (CH2), 26.0 (CH3), 26.1
(CH3), 27.2 (CH3), 30.9 (CH), 34.6 (CH2), 41.2 (CH2), 44.5 (CH2),
49.0 (C), 49.6 (CH), 55.6 (C), 73.2 (CH), 75.9 (CH), 76.9 (C),
88.7 (CH), 126.5 (3CH), 127.3 (2CH), 127.4 (C), 128.4 (CH), 128.5
(2CH), 138.5 (2CH), 146.4 (C). IR (Nujol dispersion): 3040, 1590,
1440, 1350, 730, 690 cm-1. Anal. Calcd for C30H41NO2Se: C,
68.42; H, 7.85; N, 2.66. Found: C, 68.54; H, 7.99; N, 2.75.
(3R,6aS,9R,10aR,11aS)-3-Phenylselenenylmethyl-6,6,9-tri-
methyl-decahydro-3H,7H-[1,4]oxazino[3,4-b][1,3]benzoxazine (5g).
1
Colorless oil. [R]25 ) -21.12 (c ) 1.0, CH2Cl2). H NMR (δ):
D
0.84-1.20 (m, 3H), 0.92 (d, 3H, J ) 6.5 Hz), 1.05 (s, 3H), 1.16
(s, 3H), 1.38-1.58 (m, 3H), 1.69 (m, 1H), 1.93 (m, 1H), 2.81 (dd,
1H, J1 ) 10.8 Hz, J2 ) 4.0 Hz), 2.85 (t, 1H, J ) 10.8 Hz), 2.94
(dd, 1H, J1 ) 12.6 Hz, J2 ) 6.7 Hz), 3.13 (dd, 1H, J1 ) 12.6 Hz,
J2 ) 6.5 Hz), 3.48 (td, 1H, J1 ) 10.6 Hz, J2 ) 4.1 Hz), 3.61 (dd,
1H, J1 ) 11.9 Hz, J2 ) 1.9 Hz), 3.70 (dddd, 1H, J1 ) 10.8 Hz, J2
) 6.7 Hz, J3 ) 6.5 Hz, J4 ) 4.0 Hz), 3.90 (dd, 1H, J1 ) 11.9 Hz,
J. Org. Chem, Vol. 71, No. 23, 2006 8861