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M. Tokizane et al. / Tetrahedron: Asymmetry 19 (2008) 2519–2528
(dd, J = 6.0, 10.5 Hz, 1H, 5-H), 5.78 (t, J = 7.8 Hz, 1H, 3-H), 7.25–7.49
(m, 13H, Ar-H), 7.88 (d, J = 7.5 Hz, 2H, Ar-H). 13C NMR: d (ppm)
46.2, 62.0, 84.5, 126.3, 127.1, 127.7, 128.1, 128.9, 129.0, 129.1,
129.8, 131.7, 133.2, 136.4, 142.1, 171.1. IR (neat): 3063, 3032,
1647, 1578, 1493, 1450, 1350, 1180, 1111, 1072, 1026, 907, 791,
752, 698, 667 cmꢀ1. HRMS (FAB+): calcd for C22H20NO2 [M+H]+
330.1494, found 330.1504. HPLC (Daicel Chiralcel OD-H, hexane/
2-propanol = 90:10, UV 220 nm, 0.5 mL/min): tR = 27.4 min (ma-
121.0 mg, 0.8 mmol), BH3–SMe2 (2 M in toluene, 0.8 mL,
1.6 mmol), dichloromethane (4.0 mL) at room temperature for
30 h. Reaction products were isolated by silica gel column chroma-
tography (hexane/ethyl acetate = 7:1).
(3S,5R)-cis-7c: yield 30%, colorless viscous oil; 1H NMR (CDCl3):
d (ppm) 1.42 (s, 3H, 5-Me), 2.58 (dd, J = 8.1, 12.0 Hz, 1H, 4-HH),
3.03 (dd, J = 8.7, 12.0 Hz, 1H, 4-HH), 5.82 (dd, J = 8.1, 8.7 Hz, 1H,
3-H), 7.21–7.48 (m, 13H, Ar-H), 7.94 (d, J = 7.5 Hz, 2H, Ar-H). 13C
NMR: d (ppm) 25.5, 50.3, 61.6, 88.3, 125.1, 126.4, 127.7, 127.98,
128.02, 128.7, 129.0, 129.8, 131.4, 133.7, 141.6, 142.6, 171.0. IR
(neat): 3061, 3030, 2972, 1645, 1601, 1578, 1495, 1447, 1360,
1317, 1157, 1101, 1072, 1030, 914, 762, 696, 667 cmꢀ1. HRMS
(FAB+): calcd for C23H22NO2 [M+H]+ 344.1651, found 344.1637.
HPLC (Daicel Chiralcel OD-H, hexane/2-propanol = 95:5, UV
220 nm, 0.5 mL/min): tR = 23.4 min (major), tR = 26.9 min (minor);
jor), tR = 32.1 min (minor); 65% ee. ½a D20
¼ ꢀ4:5 (c 7.08, CHCl3).
ꢁ
(3S,5S)-trans-7a: yield 24%, colorless viscous oil. 1H NMR
(CDCl3): d (ppm) 2.71 (ddd, J = 4.5, 6.3, 12.0 Hz, 1H, 4-HH), 2.93
(ddd, J = 6.3, 7.8, 12.0 Hz, 1H, 4-HH), 5.39 (t, J = 6.3 Hz, 1H, 5-H),
5.75 (dd, J = 4.5, 7.8 Hz, 1H, 3-H), 7.16–7.47 (m, 13H, Ar-H), 7.70
(d, J = 7.2 Hz, 2H, Ar-H) ppm. 13C NMR: d (ppm) 44.0, 61.2, 82.1,
126.2, 126.7, 127.9, 128.0, 128.7, 128.8, 129.1, 129.3, 131.3,
133.9, 137.9, 140.9, 169.5. IR (neat): 3059, 3032, 1647, 1578,
58% ee. ½a 2D0
¼ ꢀ5:3 (c 4.375, CHCl3).
ꢁ
1493, 1450, 1354, 1076, 1026, 988, 910, 787, 752, 698, 664 cmꢀ1
.
(3S,5S)-trans-7c: yield 14%, colorless viscous oil; 1H NMR
(CDCl3): d (ppm) 1.60 (s, 3H, 5-Me), 2.48 (dd, J = 9.3, 12.6 Hz, 1H,
4-HH), 3.40 (dd, J = 7.8, 12.6 Hz, 1H, 4-HH), 5.28 (m, 1H, 3-H),
7.07–7.45 (m, 13H, Ar-H), 7.70 (br s, 2H, Ar-H). 13C NMR: d
(ppm) 27.9, 49.0, 61.7, 88.8, 125.5, 126.4, 127.7, 127.9, 128.0,
128.7, 128.9, 129.5, 131.2, 134.2, 141.3, 142.0, 169.6. IR (neat):
3061, 3030, 2980, 1643, 1603, 1578, 1495, 1448, 1379, 1354,
1275, 1178, 1096, 1070, 1028, 910, 764, 735, 700, 667 cmꢀ1. HRMS
(FAB+): calcd for C23H22NO2 [M+H]+ 344.1651, found 344.1637.
HPLC (Daicel Chiralcel OD-H, hexane:2-propanol = 95:5, UV
220 nm, 0.5 mL/min): tR = 27.4 min (major), tR = 43.3 min (minor);
HRMS (FAB+): calcd for C22H20NO2 [M+H]+ 330.1494, found
330.1485. HPLC (Daicel Chiralcel OD-H, hexane/2-propa-
nol = 90:10, UV 220 nm, 0.5 mL/min): tR = 31.7 min (major),
tR = 36.9 min (minor); 74% ee. ½a D20
¼ ꢀ80:25 (c 3.95, CHCl3).
ꢁ
(S)-1a: recovered 29%, HPLC (Daicel Chiralpak AS-H, hexane/2-
propanol = 80:20, UV 254 nm, 0.5 mL/min): tR = 23.8 min (minor),
tR = 33.8 min (major); 21% ee. ½a D20
¼ þ52:1 (c 3.245, CHCl3).
ꢁ
4.4.2. N-Benzoyl-r-3,t-4,c-5-triphenylisoxazolidine cis-7b, N-
benzoyl-r-3,c-4,t-5-triphenylisoxazolidine trans-7b
The reaction was performed with the same procedure for 1a
using 2-isoxazoline trans-1b (239.5 mg, 0.8 mmol), (ꢀ)-norephe-
drine (4a, 121.0 mg, 0.8 mmol), BH3–SMe2 (2 M in toluene,
0.8 mL, 1.6 mmol), and dichloromethane (4.0 mL) at room temper-
ature for 30 h. Products were isolated by silica gel column chroma-
tography (hexane/ethyl acetate = 7:1).
60% ee. ½a 2D0
¼ ꢀ75:0 (c 1.92, CHCl3).
ꢁ
(S)-1c: recovered yield 53%, HPLC (Daicel Chiralpak AS-H, hex-
ane/2-propanol = 95:5, UV 254 nm, 0.3 mL/min): tR = 27.9 min
(minor), tR = 33.7 min (major); 17% ee. ½a D20
¼ þ10:0 (c 5.51, CHCl3).
ꢁ
4.4.4. N-Benzoyl-5-(2-naphthyl)-3-phenylisoxazolidines cis-7d
and trans-7d
(3S,4R,5R)-cis-7b: yield 30%; colorless crystals (from hexane/
ethyl acetate); mp 133–136 °C. 1H NMR (CDCl3): d (ppm) 3.71
(dd, J = 7.2, 9.9 Hz, 1H, 4-H), 5.03 (d, J = 9.9 Hz, 1H, 5-H), 5.84 (d,
J = 7.2 Hz, 1H, 3-H), 7.13–7.49 (m, 18H, Ar-H), 7.95 (d, J = 7.2 Hz,
2H, Ar-H). 13C NMR: d (ppm) 66.8, 70.2, 91.2, 126.0, 126.9, 127.8,
128.1, 128.2, 128.3, 128.7, 129.0, 129.1, 129.3, 129.8, 131.9,
133.0, 135.2, 136.5, 141.2, 171.0. IR (KBr): 3059, 3032, 1643,
1578, 1493, 1450, 1385, 1346, 1180, 1076, 1026, 988, 918, 752,
The reaction was performed via the same procedure for 1a
using 2-isoxazoline 1d (218.7 mg, 0.8 mmol), (ꢀ)-norephedrine
4a (121.0 mg, 0.8 mmol), BH3–SMe2 (2 M in toluene, 0.8 mL,
1.6 mmol), dichloromethane (4.0 mL) at room temperature for
45 h. Products were isolated by silica gel column chromatography
(hexane/ethyl acetate = 7:1).
(3S,5R)-cis-7d: yield 23%, colorless viscous oil; 1H NMR (CDCl3):
d (ppm) 2.53 (ddd, J = 7.2, 10.5, 12.6 Hz, 1H, 4-HH), 3.26 (ddd,
J = 6.0, 8.7, 12.6 Hz, 1H, 4-HH), 5.13 (dd, J = 6.0, 10.5 Hz, 1H, 5-H),
5.84 (dd, J = 7.2, 8.7 Hz, 1H, 3-H), 7.27–7.53 (m, 11H, Ar-H), 7.75–
7.81 (m, 4H, Ar-H), 7.91 (d, J = 7.5 Hz, 2H, Ar-H). 13C NMR: d
(ppm) 46.2, 62.1, 84.6, 124.3, 126.4, 126.68, 126.71, 126.8, 127.8,
128.0, 128.1, 128.2, 128.8, 129.1, 129.8, 131.7, 133.15, 133.19,
133.6, 133.7, 142.0, 171.1. IR (KBr): 3028, 1645, 1601, 1576,
698, 667 cmꢀ1
.
HRMS (FAB+): calcd for C28H24NO2 [M+H]+
406.1807, found 406.1794. HPLC (Daicel Chiralcel OD-H, hexane/
2-propanol = 99:1, UV 220 nm, 0.5 mL/min): tR = 36.2 min (major),
tR = 41.8 min (minor); 76% ee. ½a D20
¼ ꢀ5:3 (c 4.535, CHCl3).
ꢁ
(3S,4S,5S)-trans-7b: yield 27%; colorless viscous oil; 1H NMR
(CDCl3): d (ppm) 4.03 (dd, J = 7.2, 9.9 Hz, 1H, 4-H), 5.60 (d,
J = 9.9 Hz, 1H, 5-H), 5.88 (br d, J = 7.2 Hz, 1H, 3-H), 6.74–6.76 (m,
2H, Ar-H), 7.04–7.25 (m, 13H, Ar-H), 7.36–7.49 (m, 3H, Ar-H), 7.85
(d, J = 6.9 Hz, 2H, Ar-H). 13C NMR: d (ppm) 60.5, 67.1, 85.1, 126.6,
127.5, 127.8, 127.9, 128.2, 128.3, 128.4, 128.69, 128.74, 129.3,
129.5, 131.6, 133.6, 133.9, 136.5, 137.2, 168.8. IR (neat): 3063,
3032, 1634, 1576, 1495, 1454, 1337, 1258, 1180, 1076, 1001, 910,
1495, 1448, 1333, 1178, 1018, 910, 858, 820, 789, 698, 667 cmꢀ1
.
HRMS (FAB+): calcd for C26H22NO2 [M+H]+ 380.1651, found
380.1631. HPLC (Daicel Chiralcel OD-H, hexane/2-propanol = 95:5,
UV 220 nm, 0.5 mL/min): tR = 43.7 min (major), tR = 55.7 min (min-
or); 66% ee. ½a 2D0
¼ þ21:4 (c 3.555, CHCl3).
ꢁ
694, 664 cmꢀ1
.
HRMS (FAB+): calcd for C28H24NO2 [M+H]+
(3S,5S)-trans-7d: yield 12%, colorless crystals (from hexane/
dichloromethane), mp 101–104 °C. 1H NMR (CDCl3): d (ppm) 2.80
(ddd, J = 4.8, 6.3, 12.6 Hz, 1H, 4-HH), 3.04 (ddd, J = 6.3, 8.1,
12.6 Hz, 1H, 4-HH), 5.56 (t, J = 6.3 Hz, 1H, 5-H), 5.79 (dd, J = 4.8,
8.1 Hz, 1H, 3-H), 7.22–7.78 (m, 17H, Ar-H). 13C NMR: d (ppm)
44.0, 61.1, 82.3, 124.2, 125.7, 126.3, 126.6, 127.8, 127.9, 128.0,
128.3, 128.8, 129.1, 129.3, 131.4, 133.1, 133.3, 133.9, 135.3,
140.9, 169.8. IR (KBr): 3036, 1634, 1599, 1578, 1495, 1450, 1352,
1244, 1090, 1024, 905, 847, 797, 748, 700, 669 cmꢀ1. HRMS
(FAB+): calcd for C26H22NO2 [M+H]+ 380.1651, found 380.1643.
406.1807, found 406.1778. HPLC (Daicel Chiralcel OD-H, hexane/
2-propanol = 90:10, UV 220 nm, 0.5 mL/min): tR = 16.4 min (min-
or), tR = 25.9 min (major); 71% ee. ½a D20
¼ þ86:9 (c 3.705, CHCl3).
ꢁ
(4S,5S)-trans-1b: recovered yield 41%, HPLC (Daicel Chiralcel OJ-
H, hexane/2-propanol = 90:10, UV 220 nm, 0.7 mL/min):
tR = 17.6 min (minor), tR = 29.0 min (major); 7% ee. ½a D20
¼ þ34:8
ꢁ
(c 4.855, CHCl3).
4.4.3. N-Benzoyl-3,5-diphenyl-5-methylisoxazolidines cis-7c
and trans-7c
The reaction was performed via the same method for 1a using
2-isoxazoline 1c (189.8 mg, 0.8 mmol), (ꢀ)-norephedrine (4a,
½
a 2D0
ꢁ
¼ ꢀ89:5 (c 1.755, CHCl3).
(S)-1d: recovered yield 42%, HPLC (Daicel Chiralcel OJ-R, meth-
anol/acetonitrile = 90:10, UV 254 nm, 0.1 mL/min): tR = 64.4 min