M. Darabantu et al.
FULL PAPER
c-5-Ethyl-c-2-(4-formylphenyl)-3,7-dioxa-r-1-azabicyclo[3.3.0]octane
(6c): Yield 17%, yellow oil (flash column chromatography; pentane/
acetone, 4:1). C14H17NO3 (247.29): calcd. C 67.90, H 6.87, N 5.65;
5ЈS*)-1,4-Bis{5-ethyl-3,7-dioxa-1-azabicyclo[3.3.0]oct-2-yl}benzene
(7c-unlike): Yield 62%, yellowish crystalline powder, m.p. 109Ϫ110
°C (as like form) (flash column chromatography: pentane/acetone,
found C 68.22, H 6.54, N 5.88. Rf (80% pentane/acetone) ϭ 0.50. 4:1). C20H28N2O4 (360.45): calcd. C 66.64, H 7.83, N 7.77; found
IR (CH3Cl film, NaCl): ν˜ ϭ 2965 (s), 2930 (s), 2860 (s), 1701 (s), C 66.29, H 8.11, N 7.44. Rf (80% pentane/acetone) ϭ 0.25. IR
1609 (s), 1579 (w), 1356 (m), 1298 (m), 1205 (s), 1157 (s), 1103 (s), (CH3Cl film, NaCl): ν˜ ϭ 2924 (s), 2962 (s), 2848 (s), 1460 (m), 1431
1046 (s), 1014 (s), 925 (s), 836 (s) cmϪ1
.
1Η NMR (300 MHz,
(m), 1349 (m), 1292 (m), 1209 (m), 1152 (m), 1107 (s), 1055 (s),
3
1
CDCl3, 25 °C): δ ϭ 0.90 (t, JH,H ϭ 7.5 Hz, 3 H, CH2CH3), 1.59 1013 (s), 908 (m) cmϪ1. Η NMR (600 MHz, CDCl3, 25 °C): δ ϭ
2
3
3
(m, 2 H, CH2CH3), 3.43 (d, JH,H ϭ 8.8 Hz, 1 H, 6-H-c), 3.57 (d, 0.99 [dd (app t), JH,H ϭ 7.2 Hz, 6 H, CH2CH3], 1.67 (m, JH,H
ϭ
2
2JH,H ϭ 8.5 Hz, 1 H, 4-H-t), 3.80 (d, JH,H ϭ 8.8 Hz, 1 H, 6-H-t), 7.2, 2JH,H ϭ 14.4 Hz, 4 H, CH2CH3), 1.73 (m, 3JH,H ϭ 7.2, 2JH,H ϭ
2
2
2
4.03 (d, JH,H ϭ 8.5 Hz, 1 H, 4-H-c), 4.22 (d, JH,H ϭ 6.9 Hz, 1 H,
14.4 Hz, 4 H, CH2CH3), 3.50 (d, JH,H ϭ 8.7 Hz, 2 H, 6-H, 6Ј-H-
2
2
2
8-H-c), 4.49 (d, JH,H ϭ 6.9 Hz, 1 H, 8-H-t), 5.24 (s, 1 H, 2-H-t),
c), 3.75 (d, JH,H ϭ 8.4 Hz, 2 H, 4-H, 4Ј-H-t), 3.86 (d, JH,H ϭ
3
3
2
7.62 (d, JH,H ϭ 8.1 Hz, 2 H, H arom.), 7.82 (d, JH,H ϭ 8.1, 2 H, 8.7 Hz, 2 H, 6-H, 6Ј-H-t), 4.13 (d, JH,H ϭ 8.4 Hz, 2 H, 4-H, 4Ј-
H arom.), 9.95 (s, 1 H, CHO) ppm. 13C NMR (75 MHz, CDCl3,
25 °C): δ ϭ 9.4 (1 C, CH2CH3), 30.4 (1 C, CH2CH3), 74.1 (1 C, 6.9 Hz, 2 H, 8-H, 8Ј-H-t), 5.24 (s, 2 H, 2-H, 2Ј-H-t), 7.53 (s, 4 H,
C-5), 74.4 (1 C, C-6), 76.3 (1 C, C-4), 85.6 (1 C, C-8), 98.7 (1 C,
1,4-phenylene) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ 9.4
H-c), 4.26 (d, JH,H ϭ 6.9 Hz, 2 H, 8-H, 8Ј-H-c), 4.53 (d, JH,H ϭ
2
2
C-2), 128.3 (2 C, CH arom.), 130.2 (2 C, CH arom.), 137.0 (1 C, (2 C, CH2CH3), 30.5 (2 C, CH2CH3), 73.9 (2 C, C-5, C-5Ј), 74.5 (2
Cq arom.), 147.2 (1 C, Cq arom.), 192.3 (1 C, CHO) ppm. MS (CI, C, C-6, C-6Ј), 76.4 (2 C, C-4, C-4Ј), 85.3 (2 C, C-8, C-8Ј), 99.1 (2
CH4): m/z (%) ϭ 247 (27) [Mϩ ϩ 1], 218 (90), 158 (8), 119 (29), 83 C, C-2, C-2Ј), 127.8 (4 C, CH arom.), 141.0 (2 C, Cq arom.) ppm.
(100), 56 (37).
MS (EI, 70 eV): m/z (%) ϭ 360 (55) [Mϩ], 331 (65), 248 (30), 232
(10), 218 (10), 190 (15), 142 (15), 113 (35), 105 (10), 98 (5), 91 (8),
88 (100), 77 (5).
(1R*,1ЈR*,2R*,2ЈR*,5S*,5ЈS*)-1,4-Bis{5-(hydroxymethyl)-3,7-
dioxa-1-azabicyclo[3.3.0]oct-2-yl}benzene (7a-like) and (1S*,1ЈR*,2S*,
2ЈR*,5R*,5ЈS*)-Bis-1,4-{5-(hydroxymethyl)-3,7-dioxa-1-azabicyclo-
[3.3.0]oct-2-yl}benzene (7a-unlike): Yield 27%, white crystalline
powder, m.p. 140Ϫ141 °C (flash column chromatography; EtOAc/
pentane, 3:1). C18H24N2O6 (364.40): calcd. C 59.27, H 6.58, N 7.68;
found C 59.56, H 6.33, N 7.48. Rf (75% EtOAc/pentane) ϭ 0.20.
IR (CH3Cl film, NaCl): ν˜ ϭ 3421 (s), 2867 (s), 1636 (m), 1363 (m),
(1S*,1ЈR*,2S*,2ЈR*,5R*,5ЈS*,8R*,8ЈS*)-1,4-Bis{5-methyl-8-
phenyl-3,7-dioxa-1-azabicyclo[3.3.0]oct-2-yl}benzene
(7d-unlike):
Yield 62%, white crystalline powder, m.p. 171Ϫ172 °C (flash col-
umn chromatography; pentane/acetone, 4:1). C30H32N2O4 (484.60):
calcd. C 74.28, H 6.60, N 5.78; found C 74.60, H 6.42, N 5.44. Rf
(80% pentane/acetone) ϭ 0.40. IR (CH3Cl film, NaCl): ν˜ ϭ 3412
(s), 2966 (s), 2924 (s), 2867 (s), 1649 (w), 1377 (m), 1304 (m), 1209
1088 (s), 1017 (s), 913 (m) cmϪ1. Η NMR (600 MHz, CDCl3, 25
1
°C): δ ϭ 2.20 (br. s, 2 H, OH), 3.63 (br. s, 4 H, 5-CH2O), 3.69 (d,
1
(s), 1097 (s), 1024 (s) cmϪ1. Η NMR (600 MHz, CDCl3, 25 °C):
2JH,H ϭ 9.0 Hz, 2 H, 6-H, 6Ј-H-c), 3.81 (d, JH,H ϭ 9.0 Hz, 2 H,
2
2
δ ϭ 1.27 (s, 6 H, CH3), 3.72 and 3.74 (d, JH,H ϭ 9.0 Hz, 4 H, 4-
2
4-H, 4Ј-H-t), 3.92 (d, JH,H ϭ 8.4 Hz, 2 H, 6-H, 6Ј-H-t), 4.24 (d,
2
H, 4Ј-H-t and 6-H, 6Ј-H-t), 3.89 (d, JH,H ϭ 9.0 Hz, 4 H, 4-H, 4Ј-
2JH,H ϭ 9.0 Hz, 2 H, 4-H, 4Ј-H-c), 4.26 (d, JH,H ϭ 6.8 Hz, 2 H,
2
H-c, 6-H, 6Ј-H-c), 5.58 and 5.59 (s, 4 H, 2-H, 2Ј-H-t and 8-H,
8Ј-H-t), 7.30Ϫ7.39 (m, 6 H, phenyl), 7.56 (s, 4 H, 1,4-phenylene),
7.56Ϫ7.57 (m, 4 H, phenyl) ppm. 13C NMR (75 MHz, CDCl3, 25
°C): δ ϭ 25.1 (2 C, CH3), 71.1 (2 C, C-5, C-5Ј), 76.2 and 76.3 (4
C, C-4, C-4Ј and C-6, C-6Ј), 98.2 and 98.5 (4 C, C-2, C-2Ј and C-
8, C-8Ј), 127.6 (2 C, CH arom.), 127.7 (4 C, CH arom.), 128.6 (4
C, CH arom.), 128.7 (4 C, CH arom.), 140.4 (2 C, Cq arom.), 140.7
2
8-H, 8Ј-H-c), 4.57 (d, JH,H ϭ 6.8 Hz, 2 H, 8-H, 8Ј-H-t), 5.25 (s, 2
H, 2-H, 2Ј-H-t), 7.50 (s, 4 H, 1,4-phenylene) ppm. 13C NMR
(75 MHz, CDCl3, 25 °C): δ ϭ 65.2 (2 C, 5-CH2O), 71.9 (4 C, C-6,
C-6Ј), 74.6 (2 C, C-5, C-5Ј), 74.9 (2 C, C-4, C-4Ј), 85.4 (2 C, C-8,
C-8Ј), 98.8 (2 C, C-2, C-2Ј), 127.7 (4 C, CH arom.), 140.7 (2 C, Cq
arom.) ppm. MS (EI, 70 eV): m/z (%): 350 (50) [Mϩ], 331 (68), 248
(30), 232 (12), 218 (12), 190 (15), 142 (18), 113 (35), 88 (100).
(2 C, Cq arom) ppm. MS (CI, CH4): m/z (%) ϭ 485 (100) [Mϩ
ϩ
1], 407 (38), 379 (12), 204 (56), 175 (54).
(1R*,1ЈR*,2R*,2ЈR*,5S*,5ЈS*)-1,4-Bis{5-methyl-3,7-dioxa-1-azabi-
cyclo[3.3.0]oct-2-yl}benzene (7b-like) and (1S*,1ЈR*,2S*,2ЈR*,5R*,
5ЈS*)-1,4-Bis{5-methyl-3,7-dioxa-1-azabicyclo[3.3.0]oct-2-yl}-
benzene (7b-unlike): Yield 40%, white crystalline powder, m.p.
126Ϫ127 °C (flash column chromatography; pentane/acetone, 4:1).
C18H24N2O4 (332.40): calcd. C 64.98, H 7.22, N 8.42; found C
65.22, H 6.92, N 8.36. Rf (80% pentane/acetone) ϭ 0.40. IR (CH3Cl
film, NaCl): ν˜ ϭ 2964 (s), 2928 (s), 2853 (s), 1349 (m), 1161 (m),
(1S*,1ЈR*,2S*,2ЈR*,5R*,5ЈS*,8R*,8ЈS*)-1,4-Bis{5-ethyl-8-phenyl-
3,7-dioxa-1-azabicyclo[3.3.0]oct-2-yl}benzene (7e-unlike): Yield
64%, yellow crystalline powder, m.p. 122Ϫ125 °C (flash column
chromatography; pentane/acetone, 5:1). C32H36N2O4 (512.65):
calcd. C 74.89, H 7.02, N 5.46; found C 74.52, H 6.86, N 5.22. Rf
(83% pentane/acetone) ϭ 0.40. IR (CH3Cl film, NaCl): ν˜ ϭ 3417
(s), 2963 (s), 2928 (s), 2862 (s), 1384 (m), 1306 (m), 1211 (s), 1099
1105 (s), 1054 (s), 1030 (s), 990 (m), 918 (m) cmϪ1
.
1Η NMR
1
(s), 1018 (s), 922 (m) cmϪ1. Η NMR (600 MHz, CDCl3, 25 °C):
(600 MHz, CDCl3, 25 °C): δ ϭ 1.369 (s, 3 H, CH3), 1.372 (s, 3 H,
3
3
δ ϭ 0.86 (t, JH,H ϭ 7.6 Hz, 6 H, CH2CH3), 1.53 (q, JH,H
ϭ
2
2
CH3), 3.43 (d, JH,H ϭ 9.0 Hz, 2 H, 6-H, 6Ј-H-c), 3.81 (d, JH,H
ϭ
2
7.6 Hz, 4 H, CH2CH3), 3.83 and 3.84 (d, JH,H ϭ 8.4 Hz, 4 H, 4-
H, 4Ј-H-t and 6-H, 6Ј-H-t), 3.86 and 3.87 (d, JH,H ϭ 8.4 Hz, 4 H,
2
8.4 Hz, 2 H, 4-H, 4Ј-H-t), 3.91 (d, JH,H ϭ 9.0 Hz, 2 H, 6-H, 6Ј-
2
2
2
H-t), 3.98 (d, JH,H ϭ 8.4 Hz, 2 H, 4-H, 4Ј-H-c), 4.33 (d, JH,H
ϭ
4-H, 4Ј-H-c and 6-H, 6Ј-H-c), 5.57 and 5.57 (s, 4 H, 2-H, 2Ј-H-t
and 8-H, 8Ј-H-t), 7.3Ϫ7.37 (m, 6 H, phenyl), 7.53 (s, 4 H, 1,4-
phenylene), 7.53Ϫ7.56 (m, 4 H, phenyl) ppm. 13C NMR (75 MHz,
CDCl3, 25 °C): δ ϭ 9.8 (2 C, CH2CH3), 31.3 (2 C, CH2CH3), 74.6
(4 C, C-4, C-4Ј, C-6, C-6Ј), 74.9 (2 C, C-5, C-5Ј), 97.8 and 98.0 (4
C, C-2, C-2Ј and C-8, C-8Ј), 127.5 (2 C, CH arom.), 127.6 (4 C,
CH arom.), 128.6 (4 C, CH arom.), 128.7 (4 C, CH arom.) 140.4
(2 C, Cq arom.), 140.6 (2 C, Cq arom) ppm. MS (CI, CH4): m/z
(%) ϭ 513 (100) [Mϩ ϩ 1], 483 (Ͻ 5), 435 (32), 406 (14), 218 (30),
190 (34).
2
6.6 Hz, 2 H, 8-H, 8Ј-H-c), 4.57 (d, JH,H ϭ 6.6 Hz, 2 H, 8-H, 8Ј-
H-t), 5.28 (s, 2 H, 2-H, 2Ј-H-t), 7.53 (s, 4 H, 1,4-phenylene) ppm.
13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ 24.2 (2 C, CH3), 70.3 (2
C, C-5, C-5Ј), 76.0 (2 C, C-6, C-6Ј), 78.1 (2 C, C-4, C-4Ј), 85.5 (2
C, C-8, C-8Ј), 99.4 (2 C, C-2, C-2Ј), 127.7 (4 C, CH arom.), 141.1
(2 C, Cq arom.) ppm. MS (EI, 70 eV): m/z (%) ϭ 332 (60) [Mϩ],
302 (20), 234 (40), 128 (20), 99 (38), 69 (100).
(1R*,1ЈR*,2R*,2ЈR*,5S*,5ЈS*)-1,4-Bis{5-ethyl-3,7-dioxa-1-azabi-
cyclo[3.3.0]oct-2-yl}benzene (7c-like) and (1S*,1ЈR*,2S*,2ЈR*,5R*,
2660
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2004, 2644Ϫ2661