2250
L. Troisi et al. / Tetrahedron: Asymmetry 19 (2008) 2246–2251
GC–MS m/z 226 [M+] (23), 105 (100), 78 (50); HRMS-ESI calcd for
C14H15N2O 227.11855; found 227.11860. (+)-(10S,2R,3R)-14: Yield
4.4.1. 2-[3-Phenyl-2-(1-phenylethyl)isoxazolidin-5-yl]pyridine
17
136 mg, 60.4%, yellow oil; ½a D22:3
ꢁ
¼ þ37:4 (c 0.01, CHCl3); FT-IR film
(ꢀ)-(10R,3R,5R)-trans-17: Yield 175 mg, (53%), yellow oil;
3060, 3033, 2974, 2929, 1603, 1495, 1421, 1324 cmꢀ1
;
1H NMR
½
a 2D4:0
ꢁ
¼ ꢀ50:1 (c 0.01, CHCl3); FT-IR (CHCl3) 3063, 3025, 2960,
(400 MHz, CDCl3) d 1.67 (d, J = 6.5 Hz, 3H), 3.30 (q, J = 6.5 Hz, 1H),
4.58 (s, 1H), 7.23–7.34 (m, 7H), 8.58 (d, J = 5.8 Hz, 2H); 13C NMR
(100.62 MHz, CDCl3) d 21.6, 71.2, 78.2, 121.8, 126.9, 127.8, 128.6,
139.4, 143.2, 149.8; GC–MS m/z 226 [M+] (24), 105 (100), 78
(48); HRMS-ESI calcd for C14H15N2O 227.11855; found
227.11863. (+)-(10R,2R,3R)-14: Yield 70 mg, 31%, yellow oil;
2928, 1590, 1220 cmꢀ1 1H NMR (400 MHz, CDCl3) d 1.46 (d, J =
;
6.4 Hz, 3H), 2.63–2.67 (m, 1H), 2.75 (dt, J = 7.8, 12.4 Hz, 1H),
3.87–3.93 (m, 2H), 5.26 (t, J = 7.8 Hz, 1H), 7.12–7.38 (m, 11H),
7.43 (d, J = 7.8 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 8.47 (d, J = 4.5 Hz,
1H); 13C NMR (100.62 MHz, CDCl3) d 20.2, 43.5, 65.4, 66.8, 80.2,
121.4, 122.4, 126.9, 127.1, 127.2, 127.5, 127.7, 127.9, 136.5,
141.6, 143.1, 149.1, 161.1; GC–MS m/z 330 [M+] (>1), 209 (20),
194 (19), 105 (100), 77 (12); HRMS-ESI calcd for C22H23N2O
331.18119; found 331.18121. (+)-(10R,3R,5S)-cis-17: Yield 73 mg,
½
a 2D2:3
ꢁ
¼ þ102:1 (c 0.01, CHCl3). (ꢀ)-(10R,2S,3S)-14: Yield 140 mg,
62%, yellow oil; ½a D22:3
¼ ꢀ38:1 (c 0.01, CHCl3).
ꢁ
(22%), yellow oil; ½a D24:0
ꢁ
¼ þ70:4 (c 0.02, CHCl3); FT-IR (CHCl3)
4.3.7. 4-Methyl-2-[2-(1-phenylethyl)oxaziridin-3-yl]thiazole 15
3064, 3028, 2961, 2928, 1592, 1221 cmꢀ1
;
1H NMR (400 MHz,
(ꢀ)-(10S,2S,3S)-15: Yield 58 mg, 23.8%, yellow oil;
½
a 2D3:0
ꢁ
¼
CDCl3) d 1.47 (d, J = 6.5 Hz, 3H), 2.40–2.47 (m, 1H), 3.10 (dt,
J = 8.1, 12.5 Hz, 1H), 3.87–3.93 (m, 2H), 5.12 (dd, J = 6.5, 8.1 Hz,
1H), 7.10–7.40 (m, 11H), 7.43 (d, J = 7.8 Hz, 1H), 7.58 (t,
J = 7.8 Hz, 1H), 8.46 (d, J = 4.4 Hz, 1H); 13C NMR (100.62 MHz,
CDCl3) d 20.0, 45.4, 64.5, 67.5, 79.6, 120.4, 122.3, 126.5, 127.0,
127.3, 127.9, 128.0, 128.2, 136.7, 142.4, 142.7, 148.8, 161.1; GC–
MS m/z 330 [M+] (>1), 209 (19), 194 (21), 105 (100), 77 (10);
HRMS-ESI calcd for C22H23N2O 331.18119; found 331.18115. (+)-
ꢀ60:2 (c 0.02, CHCl3); FT-IR film 3107, 3063, 3033, 2974, 2926,
1528, 1447, 1348 cmꢀ1 1H NMR (400 MHz, CDCl3) d 1.53 (d,
;
J = 6.9 Hz, 3H), 2.46 (s, 3H), 3.43 (q, J = 6.9 Hz, 1H), 5.05 (s, 1H),
6.97 (s, 1H), 7.30 (t, J = 7.2 Hz, 1H), 7.36 (t, J = 7.2 Hz, 2H), 7.44
(d, J = 7.0 Hz, 2H); 13C NMR (100.62 MHz, CDCl3) d 16.8, 19.3,
70.0, 76.8, 116.4, 126.9, 127.7, 128.4, 140.9, 153.2, 165.0; GC–MS
m/z 246 [M+] (8), 142 (23), 105 (100), 77 (48); HRMS-ESI calcd
for C13H15N2OS 247.09065; found 247.09064. (+)-(10S,2R,3R)-15:
(10S,3S,5S)-trans-17: ½a 2D4:0
ꢁ
¼ þ50:0 (c 0.01, CHCl3). (ꢀ)-(10S,3S,
Yield 185 mg, 75.2%, yellow oil; ½a D23:0
¼ þ84:6 (c 0.02, CHCl3);
ꢁ
5R)-cis-17: ½a D24:0
¼ ꢀ70:2 (c 0.01, CHCl3).
ꢁ
FT-IR film 3107, 3063, 3033, 2974, 2926, 1528, 1447, 1348 cmꢀ1
;
(+)-(10R,3S,5S)-trans-17: Yield 165 mg, (50%), yellow oil;
1H NMR (400 MHz, CDCl3) d 1.65 (d, J = 6.5 Hz, 3H), 2.37 (s, 3H),
3.30 (q, J = 6.5 Hz, 1H), 5.01 (s, 1H), 6.91 (s, 1H), 7.26–7.40 (m,
5H); 13C NMR (100.62 MHz, CDCl3) d 16.9, 21.5, 71.2, 76.7, 117.3,
121.1, 127.1, 129.2, 149.9, 154.5, 166.2; GC–MS m/z 246 [M+]
(9), 142 (22), 105 (100), 77 (49); HRMS-ESI calcd for C13H15N2OS
247.09065; found 147.09059. (+)-(10R,2R,3R)-15: Yield 57 mg,
½
a 2D4:0
ꢁ
¼ þ21:2 (c 0.01, CHCl3); FT-IR (CHCl3) 3065, 3020, 2960,
2930, 1590, 1222 cmꢀ1 1H NMR (400 MHz, CDCl3) d 1.52 (d,
;
J = 6.4 Hz, 3H), 2.72–2.78 (m, 1H), 2.94 (dt, J = 7.9, 12.5 Hz, 1H),
4.03 (q, J = 6.3 Hz, 1H), 4.25 (dd, J = 4.2, 7.6 Hz, 1H), 5.24 (t,
J = 7.9 Hz, 1H), 7.10–7.38 (m, 11H), 7.51 (d, J = 7.8 Hz, 1H), 7.68
(t, J = 7.8 Hz, 1H), 8.57 (d, J = 4.6 Hz, 1H); 13C NMR (100.62 MHz,
CDCl3) d 20.3, 43.5, 65.5, 66.8, 80.2, 121.3, 122.4, 126.8, 127.1,
127.2, 127.6, 127.7, 128.0, 136.5, 141.6, 143.0, 149.1, 161.0; GC–
MS m/z 330 [M+] (>1), 209 (16), 194 (18), 105 (100), 77 (14);
HRMS-ESI calcd for C22H23N2O 331.18119; found 331.18124. (ꢀ)-
23%, yellow oil; ½a D23:0
ꢁ
¼ þ58:8 (c 0.01, CHCl3). (ꢀ)-(10R,2S,3S)-15:
Yield 187 mg, 76%, yellow oil; ½a D23:0
¼ ꢀ84:1 (c 0.01, CHCl3).
ꢁ
4.3.8. 2-[2-(1-Phenylethyl)oxaziridin-3-yl]benzothiazole 16
(ꢀ)-(10S,2S,3S)-16: Yield 56 mg, 20%, yellow oil; ½a 2D1:0
¼ ꢀ55:6
ꢁ
(10R,3S,5R)-cis-17: Yield 63 mg, (19%), yellow oil; ½a 2D4:0
¼ ꢀ26:0
ꢁ
(c 0.02, CHCl3); FT-IR (CHCl3) 3068, 3038, 2993, 2931, 1603,
(c 0.02, CHCl3); FT-IR (CHCl3) 3065, 3020, 2961, 2934, 1593,
1523, 1496, 1354, 1317 cmꢀ1 1H NMR (400 MHz, CDCl3) d 1.59
;
1222 cmꢀ1 1H NMR (400 MHz, CDCl3) d 1.58 (d, J = 6.5 Hz, 3H),
;
(d, J = 7.0 Hz, 3H), 3.52 (q, J = 7.0, 1H), 5.19 (s, 1H), 7.32–7.52 (m,
7H), 7.91 (d, J = 7.7 Hz, 1H), 8.08 (d, J = 8.3 Hz, 1H); 13C NMR
(100.62 MHz, CDCl3) d 19.4, 70.2, 77.3, 122.1, 123.6, 126.1, 126.3,
127.0, 127.9, 128.6, 135.6, 140.8, 167.0, 170.1; GC–MS m/z 282
[M+] (8), 267 (23), 162 (70), 135 (50), 120 (100); HRMS-ESI calcd
for C16H15N2OS 283.09065; found 283.09061. (+)-(10S,2R,3R)-16:
2.43–2.50 (m, 1H), 3.27 (dt, J = 8.3, 12.7 Hz, 1H), 4.11(q,
J = 6.5 Hz, 1H), 4.26 (dd, J = 5.9, 8.1 Hz, 1H), 5.41 (t, J = 8.3 Hz,
1H), 7.11–7.25 (m, 9H), 7.29–7.33 (m, 2H), 7.40 (d, J = 7.8 Hz,
1H), 7.59 (t, J = 7.8 Hz, 1H), 8.49 (d, J = 4.4 Hz, 1H); 13C NMR
(100.62 MHz, CDCl3) d 20.1, 45.5, 64.4, 67.5, 79.5, 120.4, 122.2,
126.6, 127.1, 127.3, 127.9, 128.1, 128.2, 136.7, 142.4, 142.7,
148.7, 161.2; GC–MS m/z 330 [M+] (>1), 209 (22), 194 (17), 105
(100), 77 (9); HRMS-ESI calcd for C22H23N2O 331.18119; found
Yield 189 mg, 67.0%, yellow oil; ½a D21:0
¼ þ80:3 (c 0.01, CHCl3);
ꢁ
FT-IR (CHCl3) 3068, 3038, 2993, 2931, 1603, 1523, 1496, 1354,
1317 cmꢀ1 1H NMR (400 MHz, CDCl3) d 1.70 (d, J = 6.6 Hz, 3 H),
;
331.18117. (ꢀ)-(10S,3R,5R)-trans-17: ½a 2D4:0
¼ ꢀ21:0 (c 0.02, CHCl3).
ꢁ
3.38 (q, J = 6.6 Hz, 1H), 5.14 (s, 1H), 7.33–7.53 (m, 7H), 7.90 (d,
J = 7.8 Hz, 1H), 8.08 (d, J = 8.2 Hz, 1H); 13C NMR (100.62 MHz,
CDCl3) d 18.8, 69.2, 77.2, 121.4, 124.3, 126.3, 126.9, 128.3, 129.4,
133.1, 137.1, 152.8, 167.1, 170.1. GC–MS m/z 282 [M+] (10), 267
(22), 162 (68), 135 (51), 120 (100); HRMS-ESI calcd for C16H15N2OS
(+)-(10S,3R,5S)-cis-17: ½a 2D4:0
¼ þ26:3 (c 0.02, CHCl3).
ꢁ
4.4.2. 2-[3-(4-Methoxyphenyl)-2-(1-phenylethyl)isoxazolidin-
5-yl]pyridine 18
(+)-(10S,3S,5S)-trans-18: Yield 194 mg, (54%), yellow oil;
283.09065; found 283.09058. (+)-(10R,2R,3R)-16: ½a 2D1:0
¼ þ56:0 (c
ꢁ
½
a 2D1:0
ꢁ
¼ þ55:1 (c 0.02, CHCl3); FT-IR (CHCl3) 3065; 3004; 2959;
0.01, CHCl3). (ꢀ)-(10R,2S,3S)-16: ½a 2D1:0
¼ ꢀ80:7 (c 0.01, CHCl3).
ꢁ
2935; 1510; 1247; 1108 cmꢀ1 1H NMR (400 MHz, CDCl3) d 1.56
;
(d, J = 6.3 Hz, 3H), 2.50–2.58 (m, 1H), 2.71–2.77 (m, 1H), 3.80 (s,
3H), 4.10 (q, J = 6.3 Hz, 1H), 4.21 (dd, J = 7.6 Hz, 1H), 5.27 (t,
J = 7.7 Hz, 1H), 6.90 (d, J = 8.5 Hz, 2H), 7.17–7.40 (m, 8H), 7.57 (d,
J = 7.6 Hz, 1H), 7.71 (t, J = 7.6 Hz, 1H), 8.49 (d, J = 4.5 Hz, 1H); 13C
NMR (100.62 MHz, CDCl3) d 20.2, 43.6, 54.8, 65.3, 65.5, 79.8,
113.8, 121.3, 121.9, 127.4, 128.1, 128.2, 128.8, 133.8, 136.8,
143.1, 149.1, 158.5, 162.1; GC–MS m/z 360 [M+] (<1), 240 (5),
239 (24), 238 (17), 224 (30), 134 (10), 105 (100), 77 (32); HRMS-
ESI calcd for C23H25N2O2 361.19175; found 361.19169. (ꢀ)-
4.4. General procedure for the synthesis of isoxaziridines 17
and 18
A solution of alkene (1.5 mmol) and oxaziridine 9 or 11
(1.0 mmol) in toluene (10 mL) was refluxed under magnetic stir-
ring overnight. Afterwards, TLC showed the reaction to be com-
plete. The solution was cooled to rt, and concentrated in vacuo to
dryness. The crude product was purified by flash chromatography
(silica gel, petroleum ether/ethyl acetate = 9:1) to afford the pure
isoxazolidines 17 and 18 (total yields: 69–77%).
(10S,3S,5R)-cis-18: Yield 65 mg, (18%), yellow oil; ½a 2D1:0
¼ ꢀ65:6
ꢁ
(c 0.01, CHCl3); FT-IR (CHCl3) 3063, 3003, 2967, 2931, 1513,