Jul-Aug 2008
Regio- and Stereoselective Synthesis of Isoxazolidines
961
J = 5.4, 10.8 Hz, 1 H), 4.44 (d, J = 10.8 Hz, 1 H), 4.95 (dd, J =
2.7, 5.4 Hz, 1 H), 7.32-7.36 (m, 5 H); 13C nmr (67.8 MHz,
CDCl3): ꢀ 24.6, 26.2, 61.3, 64.9, 65.7, 68.8, 70.9, 74.2, 79.9,
110.3, 127.6, 128.4, 128.6, 136.0; ir (KBr): 3074, 2981, 1492,
1454, 1225, 1150, 1048, 821, 731 cm-1; ms (FAB): m/z 356
(M+H)+; hrms (ESI): m/z C16H22NO6S (M+H)+. Calcd:
356.1167. Found: 356.1164.
(3R,3aR,6aR)-3-[(S)-2-(benzoxy)benzyl]-2-benzyl--4,5-oxa-
thiain-4,4-dioxide[3,4-d]isoxazolidine (7d). White solid; mp
21
1
146-148 °C; [ꢁ]D +9.3° (c 1.5, CHCl3); H nmr (400 MHz,
CDCl3): ꢀ 3.79 (dd, J = 5.6, 6.8 Hz, 1 H), 3.93 (dd, J = 4.8, 6.8
Hz, 1 H), 3.99 (d, J = 14.0, 1 H), 4.18 (dd, J = 3.6. 11.2 Hz, 1
H), 4.32 (q, J = 11.2 Hz, 2 H), 4.42 (d, J = 14.4 Hz, 1 H), 4.55
(d, J = 12.0 Hz, 1 H), 4.57 (d, J = 6.8 Hz, 1 H), 4.72 (dd, J = 2.8,
6.4 Hz, 1 H), 7.27-7.46 (m, 15 H); 13C nmr (100.6 MHz, CDCl3):
ꢀ 62.3, 65.9, 68.6, 70.7, 72.9, 79.7, 81.2, 127.5, 127.9, 128.0,
128.1, 128.3, 128.5, 128.8, 129.0, 129.2, 136.7, 137.1, 137.2; ir
(KBr): 3037, 2881, 1457, 1374, 1205, 945, 770 cm-1; ms (FAB):
m/z 452 (M+H)+; hrms (ESI): m/z C25H26NO5S (M+H)+. Cacld:
452.1531. Found: 452.1547.
(3R,3aR,6aR)-2-Benzyl-3-(1-deoxy-2,3:4,5-di-O-isoprop-
ylidene-D-mannito-1-yl)-4,5-oxathiain-4,4-dioxide[3,4-d]-
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1
isoxazolidine (7b). Thick oil; [ꢁ]D +14.7° (c 1.0, CHCl3); H
nmr (270 MHz, CDCl3): ꢀ 1.35 (s, 6 H), 1.44 (s, 6 H), 3.76 (t, J
= 7.6 Hz, 1 H), 3.87 (dd, J = 2.2, 5.7 Hz, 1 H), 3.92-4.08 (m, 4
H), 4.16 (q, J = 5.7 Hz, 1 H), 4.26 (d, J = 13.8 Hz, 1 H), 4.37
(dd, J =3.3, 11.1 Hz, 1 H), 4.43 (d, J = 4.3 Hz, 1 H), 4.45 (d, J =
10.8 Hz, 1 H), 4.98 (dd, J = 3.0, 6.8 Hz, 1 H), 7.31-7.38 (m, 5
H); 13C nmr (67.8 MHz, CDCl3): ꢀ 25.3, 26.4, 26.9, 27.0, 61.3,
63.5, 67.9, 69.5, 69.7, 77.1, 78.1, 78.8, 80.3, 110.0, 110.3, 127.7,
128.3, 129.0, 135.9; ir (KBr): 2928, 2860, 2363, 1462, 1379,
1213, 1167, 1084, 851, 711 cm-1; ms (FAB): m/z 456 (M+H)+;
hrms (ESI): m/z C21H29NO8NaS (M+Na)+ Calcd: 478.1512.
Found: 478.1516.
3S,3aS,6aS)-3-[(S)-2-(Benzoxy)benzyl]-2-benzyl-4,5-oxa-
thiain-4,4-dioxide[3,4-d]isoxazolidine (8d). White solid; mp
21
1
132-134 °C; [ꢁ]D +24.2° (c 1.5, CHCl3); H nmr (400 MHz,
CDCl3): ꢀ 3.60 (d, J = 14.0 Hz, 1 H), 3.75 (dd, J = 5.2, 6.0 Hz, 1
H), 3.79 (d, J = 13.6 Hz, 1 H), 4.29 (d, J = 12.0 Hz, 1 H), 4.30
(dd, J = 5.6, 11.2 Hz, 1 H), 4.31 (dd, J = 3.6, 7.6 Hz, 1 H), 4.33
(d, J = 6.0 Hz, 1 H), 4.41 (d, J = 11.2 Hz, 1 H), 4.60 (d, J = 12.0
Hz, 1 H), 4.88 ( dd, J = 3.2, 6.8 Hz, 1 H), 7.15-7.44 (m, 10 H);
13C nmr (100.6 MHz, CDCl3): ꢀ 61.6, 65.9, 68.9, 70.5, 74.4,
79.4, 79.7, 127.5, 127.6, 128.0, 128.3, 128.5, 128.8, 129.0,
129.1, 136.5, 137.3, 137.4; ir (KBr): 3037, 2850, 1503, 1349,
1159, 1019, 699 cm-1; hrms (ESI): m/z C25H26NO5S (M+H)+.
Calcd: 452.1531. Found: 452.1546. Anal. Cacld. for
C25H25NO5S: C, 66.50; H, 5.58; N, 3.10. Found: C, 66.40; H,
5.53; N, 3.02.
(3S,3aS,6aS)-2-Benzyl-3-(1-deoxy-2,3:4,5-di-O-isopropyli-
dene-D-mannito-1-yl)-4,5-oxathiain-4,4-dioxide[3,4-d]-isoxa-
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1
zolidine (8b). Thick oil; [ꢁ]D –38.7° (c 1.0, CHCl3); H nmr
(270 MHz, CDCl3): ꢀ 1.26 (s, 3 H), 1.38 (s, 3 H), 1.40 (s, 3 H),
1.44 (s, 3 H), 3.58 (dd, J = 5.9, 7.8 Hz, 1 H), 3.83-3.93 (m, 2 H),
3.98-4.11 (m, 2 H), 4.18-4.31 (m, 2 H), 4.28 (dd, J = 2.4, 8.4 Hz,
1 H), 4.39 (d, J = 4.9 Hz, 1 H), 4.41 (d, J = 6.5 Hz, 1 H), 4.65 (d,
J = 14.3 Hz, 1 H), 4.94 (dd, J = 3.0, 6.8 Hz, 1 H), 7.27-7.37 (m,
5 H); 13C nmr (67.8 MHz, CDCl3): ꢀ 25.6, 26.0, 26.7, 27.1, 61.5,
64.8, 68.3, 68.9, 71.4, 77.2, 79.7, 79.8, 81.8, 110.4, 110.5, 127.2,
128.1, 128.5, 137.2; ir (KBr): 2933, 2860, 2368, 1742, 1457,
1384, 1224, 1167, 1073, 856, 700 cm-1; hrms (ESI): m/z
C21H29NO8NaS (M+Na)+. Calcd: 478.1511. Found: 478.1508;
Anal. Calcd. for C21H29NO8S: C, 55.37; H, 6.42; N, 3.07. Found:
C, 55.29; H, 6.37; N, 3.12.
(3R,3aR,6aR)-2-Benzyl-3-[(1R)-myrtenyl]-4,5-oxathiain-4,
4-dioxide[3,4-d]isoxazolidine (7e). White solid; mp 213-215
21
1
°C; [ꢁ]D –80.7° (c 1.0, CHCl3); H nmr (400 MHz, CDCl3): ꢀ
0.90 (s, 3 H), 1.12 (d, J = 8.4 Hz, 1 H), 1.35 (s, 3 H), 2.19 (m, 1
H), 2.34-2.42 (m, 3 H), 2.49 (m, 1 H), 3.68 (d, J = 14.4 Hz, 1 H),
3.71 (d, J = 10.0 Hz, 1 H), 3.85 (t, J = 7.2 Hz, 1 H), 4.09 (d, J =
14.4 Hz, 1 H), 4.72 (dd, J = 3.6, 11.3 Hz, 1 H), 4.38 (d, J = 6.8
Hz, 1 H), 4.91 (dd, J = 2 .8, 6.8 Hz, 1 H), 5.88 (m, 1 H), 7.30
(m, 5 H); 13C nmr (100.6 MHz, CDCl3): ꢀ 21.8, 26.0, 31.5, 31.8,
38.0, 40.5, 41.9, 59.6, 65.4, 68.9, 74.6, 79.5, 126.6, 127.5, 128.4,
128.5, 137.0, 140.8; ir (KBr): 2959, 2928, 1742, 1463, 1379,
1163, 954, 866 cm-1; hrms (ESI): m/z C20H25NO4NaS (M+Na)+.
Cacld: 398.1402. Found: 398.1421; Anal. Cacld. for
C20H25NO4S: C, 63.98; H, 6.71; N, 3.73. Found: C, 63.90; H,
6.68; N, 3.68.
(3R,3aR,6aR)-3-[(S)-2-(Benzoxy)ethyl]-2-benzyl-4,5-oxa-
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thiain-4,4-dioxide[3,4-d]isoxazolidine (7c). Thick oil; [ꢁ]D
-25.6° (c 1.3, CHCl3); 1H nmr (400 MHz, CDCl3): ꢀ 1.19 (d, J =
6.8 Hz, 3 H), 3.63 (m, 1 H), 3.74 (dd, J = 5.2, 6.8 Hz, 1 H), 3.99
(dd, J = 6.4, 12.0 Hz, 1 H), 4.03 (d, J = 13.6 Hz, 1 H), 4.21 (d, J
= 14.0 Hz, 1 H), 4.30 (dd, J = 3.2, 11.2 Hz, 1 H), 4.41 (d, J =
10.8 Hz, 1 H), 4.55 (q, J = 12.0 Hz, 2 H), 4.90 (dd, J = 3.2, 6.4
Hz, 1 H), 7.24-7.36 (m, 10 H); 13C nmr (100.6 MHz, CDCl3): ꢀ
15.7, 61.8, 65.2, 69.1, 70.9, 71.6, 73.6, 80.1, 127.6, 127.7, 127.8,
128.3, 128.4, 128.9, 136.4, 137.6; ir (KBr): 3041, 2881, 2358,
1964, 1731, 1612, 1498, 1457, 861 cm-1; hrms (ESI): m/z
C20H24NO5S (M+H)+. Calcd: 390.1374. Found: 390.1389; Anal.
Calcd. for C20H23NO5S: C, 61.68; H, 5.95; N, 3.60. Found: C,
61.58; H, 6.03; N. 3.54.
(3S,3aS,6aS)-2-Benzyl-3-[(1R)-myrtenyl]-4,5-oxathiain-4,4-
dioxide[3,4-d]isoxazolidine (8e). White solid; mp 153-155
21
1
°C; [ꢁ]D +12.2° (c 1.3, CHCl3); H nmr (400 MHz, CDCl3):
ꢀ 0.92 (s, 3 H), 1.11 (d, J = 8.4 Hz, 1 H), 1.34 (s, 3 H), 2.16
(m, 1 H), 2.33-2.41 (m, 3 H), 2.50 (m, 1 H), 3.70 (d, J = 2.8
Hz, 1 H), 3.72 (dd, J = 2.8, 14.4 Hz, 1 H), 3.73 (d, J = 4.8 Hz,
1 H), 4.05 (d, J = 14.4 Hz, 1 H), 4.27 (dd, J = 3.6, 11.2 Hz, 1
H), 4.37 (d, J = 10.8 Hz, 1 H), 4.92 (dd, J = 3.6, 6.8 Hz, 1 H),
5.88 (m, 1 H), 7.27-7.35 (m, 5 H); 13C nmr (100.6 MHz,
CDCl3): ꢀ 21.2, 25.9, 31.6, 37.9, 40.4, 41.4, 59.5, 64.5, 69.0,
75.2, 79.4, 127.3, 127.6, 128.4, 128.6, 237.0, 140.6; ir (KBr):
2954, 2835, 1368, 1213, 1156, 944, 877 cm-1; ms (FAB): m/z
376 (M+H)+; hrms (ESI): m/z C20H25NO4NaS (M+Na)+ Cacld:
398.1402. Found: 398.1407.
(3S,3aS,6aS)-3-[(S)-2-(Benzoxy)ethyl]-2-benzyl-4,5-oxathi-
21
ain-4,4-dioxide[3,4-d]isoxazolidine (8c). Thick oil; [ꢁ]D
+18.4° (c 1.35, CHCl3); 1H nmr (400 MHz, CDCl3): ꢀ 1.27 (d, J
= 6.0 Hz, 3 H), 3.44 (dd, J = 2.4, 5.6 Hz, 1 H), 3.65 (m, 1 H),
3.93 (d, J = 13.6 Hz, 1 H), 4.15 (d, J = 14.0 Hz, 1 H), 4.27 (dd, J
= 3.2, 11.2 Hz, 1 H), 4.32 (dd, J = 5.6, 7.2 Hz, 1 H), 4.39 (d, J =
11.6 Hz, 1 H), 4.65 (d, J = 2.0 Hz, 2 H), 4.88 (dd, J = 3.2, 6.8
Hz, 1 H), 7.21-7.41 (m, 10 H); 13C nmr (100.6 MHz, CDCl3): ꢀ
18.2, 60.9, 63.7, 69.1, 71.4, 71.8, 74.7, 80.0, 127.5, 127.6, 128.2,
128.4, 128.5, 128.6, 136.5, 137.9; ir (KBr): 3042, 2881, 2368,
1721, 1498, 1457, 13s79, 1156, 861 cm-1; hrms (ESI): m/z
C20H24NO5S (M+H)+. Calcd: 390.1374. Found: 390.1385.
Acknowledgement. We are grateful to the grants from the
program for Innovative Research Team in Science and
Technology in Fujian Province University and the Hong Kong
Baptist University (PRG/01-02/II-41) for financial support.