0.48 (1:1 hexane–EtOAc) (Found: C, 53.8; H, 6.1; N, 4.0.
C15H20F3NO2S requires C, 53.72; H, 6.01; N, 4.18%); [α]D24
Ϫ40.2 (c 1.7, CHCl3); νmax(neat)/cmϪ1 1154, 1298 and 1368; δH
0.99 (3 H, d, J 6.6), 1.01 (3 H, d, J 6.6), 1.30 (3 H, d, J 6.5), 2.05
(3 H, s), 2.94 (1 H, septet, J 6.6), 4.53 (1 H, q, J 6.5), 6.85 (1 H,
dq, J 15.4 and 6.2), 7.39 (1 H, dq, J 15.4 and 1.6) and 8.08–7.40
(4 H, m); δC 17.7, 18.3, 20.3, 31.4, 49.2, 56.4, 121.8 (q, J 271),
127.8, 128.8 (q, J 37), 129.9, 135.3, 135.8, 140.8 (q, J 6) and
148.9; δF Ϫ65.4 (d, J 5); m/z (EI) 336 (Mϩ, 2%), 320 (13) and
174 (100).
3.6), 5.47 (1 H, dd, J 6.9 and 3.6) and 8.23–6.92 (14 H, m);
δC 11.9, 40.7, 57.4, 72.9, 74.5 (q, J 34), 75.7, 119.5, 124.0 (q,
J 284), 125.5, 127.8, 128.4, 128.9, 129.0, 129.0, 129.6, 132.9,
134.8, 136.0, 136.7, 146.0 and 148.1; δF Ϫ74.7 (d, J 7); m/z
(CI) 505 (M ϩ Hϩ).
(3S,4S,5R)-2-Butyl-4-{2-[(1S)-1-(dimethylamino)ethyl]-
phenylsulfonyl}-3-phenyl-5-(trifluoromethyl)isoxazolidine
10c
and (3R,4R,5S)-2-butyl-4-{2-[(1S)-1-(dimethylamino)ethyl]-
phenylsulfonyl}-2-methyl-3-phenyl-5-(trifluoromethyl)isoxazo-
lidine 11c. A mixture of isomers 10c and 11c was obtained as
above from compound 8a (307 mg, 1.00 mmol) and N-butyl-C-
phenylnitrone 9c (177 mg, 1.00 mmol). Isomers 10c and 11c
were separated by chromatography on a silica gel column. The
first component gave compound 10c as a yellow oil (271 mg,
56%); Rf 0.38 (2:1 hexane–EtOAc) (Found: C, 59.8; H, 6.4; N,
5.5. C24H31F3N2O3S requires C, 59.49; H, 6.45; N, 5.78%); [α]D21
114.0 (c 1.7, CHCl3); νmax (neat)/cmϪ1 1154, 1279 and 2959; δH
0.82 (3 H, t, J 7.2), 1.08 (3 H, d, J 6.7), 1.66–1.27 (4 H, m), 1.71
(6 H, s), 2.74 (1 H, dt, J 13.0 and 7.6), 2.88–2.75 (1 H, m), 4.34
(1 H, d, J 7.9), 4.45 (1 H, q, J 6.7), 4.55 (1 H, qd, J 7.4 and 3.4),
5.36 (1 H, dd, J 7.9 and 3.4) and 8.12–7.28 (9 H, m); δC 11.3,
13.8, 20.1, 29.7, 40.2, 55.9, 57.0, 71.0, 74.8, 76.3 (q, J 35), 123.8
(q, J 285), 127.9, 129.0, 129.1, 129.1, 129.5, 131.9, 134.6, 136.2,
137.3 and 145.5; δF Ϫ75.8 (d, J 7); m/z (CI) 485 (M ϩ Hϩ). The
second component gave isomer 11c as a yellow solid (73 mg,
15%); mp 70–73 ЊC (Found: C, 59.6; H, 6.3; N, 5.8%); [α]D23
Ϫ78.33 (c 2.0, CHCl3); νmax(KBr)/cmϪ1 1152, 1281 and 2957; δH
0.78 (3 H, t, J 7.2), 1.15 (3 H, d, J 6.6), 1.69–1.21 (4 H, m), 1.77
(6 H, s), 2.53 (1 H, dt, J 12.8 and 7.7), 2.80–2.68 (1 H, m), 3.95
(1 H, d, J 7.7), 4.44 (1 H, q, J 6.6), 5.08 (1 H, qd, J 7.4 and 3.7),
5.16 (1 H, dd, J 7.7 and 3.7) and 8.20–6.94 (9 H, m); δC 13.2,
13.7, 20.1, 29.6, 41.1, 55.6, 57.8, 73.5, 74.5 (q, J 34), 74.9, 124.2
(q, J 285), 127.6, 128.7 (2 C), 128.8, 129.1, 129.4, 132.5, 135.7,
136.1 and 146.0; δF Ϫ75.0 (d, J 7); m/z (CI) 485 (M ϩ Hϩ).
68:32 Diastereomeric mixture of (3S,4S,5R)-4-{2-[(1S)-1-
piperidinoethyl]phenylsulfonyl}-2-methyl-3-phenyl-5-(tri-
fluoromethyl)isoxazolidine 12 and (3R,4R,5S)-4-{2-[(1S)-1-
piperidinoethyl]phenylsulfonyl}-2-methyl-3-phenyl-5-(trifluoro-
methyl)isoxazolidine 13. This was obtained as above from
compounds 8b (347 mg, 1.00 mmol) and 9a (135 mg, 1.00
mmol) as a yellow oil (357 mg, 74%); Rf 0.39 (3:1 hexane–
EtOAc) (Found: C, 59.9; H, 6.3; N, 5.5. C24H29F3N2O3S
requires C, 59.74; H, 6.06; N, 5.81%); νmax(neat)/cmϪ1 1154,
1279 and 2936; δH 1.03 (2.0 H, d, J 6.6), 1.16 (1.0 H, d, J 6.4),
1.22–1.50 (6.0 H, m), 1.90–2.33 (4.0 H, m), 2.62 (1.0 H, s), 2.71
(2.0 H, s), 3.89 (0.32 H, q, J 6.4), 3.97 (0.32 H, d, J 7.9), 4.08
(0.68 H, q, J 6.6), 4.25 (0.68 H, d, J 7.9), 4.46 (0.32 H, dd, J 7.9
and 3.9), 4.68 (0.68 H, qd, J 7.6 and 3.8), 4.73 (0.68 H, dd, J 7.9
and 3.8), 5.09 (0.32 H, qd, J 7.2 and 3.9) and 7.02–8.07 (9.0 H,
m); δC 16.9, 20.7, 24.5 (combined peak), 26.0 (combined peak),
42.9, 43.1, 50.8, 51.9, 58.6, 60.2, 73.0, 75.1, 74.5 (q, J 34), 75.2
(combined peak), 76.8 (q, J 34), 123.7 (q, J 284), 124.1 (q, J
285), 127.3, 127.6, 128.5, 128.8, 129.2 (combined peak), 129.2,
129.8, 130.2, 131.0, 131.5, 134.7, 134.9, 135.1, 135.1, 135.6,
135.9, 146.7 and 148.3; δF Ϫ75.7 (d, J 7, major), Ϫ75.3 (d, J 7,
minor); m/z (CI) 483 (M ϩ Hϩ).
General procedure for 1,3-dipolar cycloaddition of amines 8a–c
with nitrones 9a–c
A solution of compound 8a–c (1.00 mmol) and a nitrone
9a–c (1.00 mmol) in toluene (5 cm3) was heated at 90 ЊC
under argon in a sealed tube for 12 h. After the solvent was
removed under reduced pressure, the residue was chromato-
graphed on a silica gel column (2:1 hexane–AcOEt). No
1
regioisomers of the cycloadducts were detected by H NMR
spectroscopy of the crude products. For the yields and de-
values, see Table 1.
(3S,4S,5R)-4-{2-[(1S)-1-(Dimethylamino)ethyl]phenyl-
sulfonyl}-2-methyl-3-phenyl-5-(trifluoromethyl)isoxazolidine
10a and (3R,4R,5S)-4-{2-[(1S)-1-(dimethylamino)ethyl]-phenyl-
sulfonyl}-2-methyl-3-phenyl-5-(trifluoromethyl)isoxazolidine
11a. A mixture of heterocycles 10a and 11a was obtained as
above from compound 8a (307 mg, 1.00 mmol) and N-methyl-
C-phenylnitrone 9a (135 mg, 1.00 mmol). Isomers 10a and 11a
were separated by chromatography on a silica gel column. The
first component gave compound 10a as a solid (301 mg, 68%);
mp 101–103 ЊC (Found: C, 57.0; H, 5.8; N, 6.3. C21H25F3-
N2O3S requires C, 57.00; H, 5.69; N, 6.33%); [α]2D7 76.8 (c 2.1,
CHCl3); νmax(KBr)/cmϪ1 1155, 1310 and 1454; δH 1.09 (3 H, d, J
6.7), 1.72 (6 H, s), 2.70 (3 H, s), 4.26 (1 H, d, J 8.2), 4.47 (1 H, q,
J 6.7), 4.56 (1 H, qd, J 7.4 and 3.6), 5.43 (1 H, dd, J 8.2 and 3.6)
and 7.66–7.30 (9 H, m); δC 11.0, 40.2, 43.1, 56.9, 72.8, 75.0, 76.4
(q, J 34), 123.7 (q, J 284), 127.9, 129.1, 129.2 (2 C), 129.5, 131.9,
134.7, 136.1, 136.8 and 145.5; δF Ϫ75.9 (d, J 7); m/z (CI) 443
(M ϩ Hϩ). The second component gave compound 11a as a
yellow solid (53 mg, 12%); mp 102–105 ЊC (Found: C, 57.4; H,
5.7; N, 6.2%); [α]D27 Ϫ57.8 (c 1.6, CHCl3); νmax(KBr)/cmϪ1
1152, 1281 and 1456; δH 1.17 (3 H, d, J 6.7), 1.81 (6 H, s), 2.61 (3
H, s), 3.89 (1 H, d, J 7.7), 4.46 (1 H, q, J 6.7), 5.09 (1 H, qd, J
7.4 and 3.8), 5.18 (1 H, dd, J 7.7 and 3.8) and 8.19–6.97 (9 H,
m); δC 13.2, 41.2, 42.9, 57.8, 74.7 (q, J 34), 75.1, 75.3, 124.1 (q, J
284), 127.7, 128.7, 128.8 (2 C), 129.1, 129.5, 132.4, 134.7, 135.0,
136.0 and 145.7; δF Ϫ75.1 (d, J 7); m/z (CI) 443 (M ϩ Hϩ).
(3S,4S,5R)-4-{2-[(1S)-1-(Dimethylamino)ethyl]phenyl-
sulfonyl}-2,3-diphenyl-5-(trifluoromethyl)isoxazolidine 10b and
(3R,4R,5S)-4-{2[(1S)-1-(dimethylamino)ethyl]phenyl-
sulfonyl}-2,3-diphenyl-5-(trifluoromethyl)isoxazolidine 11b.
A
mixture of isomers 10b and 11b was obtained as above from
compound 8a (307 mg, 1.00 mmol) and C,N-diphenylnitrone 9b
(197 mg, 1.00 mmol). Isomers 10b and 11b were separated by
chromatography on a silica gel column. The first component
gave compound 10b as an orange oil (313 mg, 62%); Rf 0.50
(2:1 hexane–EtOAc) (Found: C, 61.79; H, 5.43; N, 5.59.
C26H27F3N2O3S requires C, 61.89; H, 5.39; N, 5.55%); [α]D24
113.9 (c 1.8, CHCl3); νmax(neat)/cmϪ1 1134, 1240 and 1580;
δH 1.11 (3 H, d, J 6.6), 1.70 (6 H, s), 4.56 (1 H, q, J 6.6), 4.72
(1 H, qd, J 7.3 and 3.5), 5.09 (1 H, d, J 7.1), 5.65 (1 H, dd, J
7.1 and 3.5) and 8.15–7.02 (14 H, m); δC 10.6, 40.0, 56.9,
69.8, 75.5, 76.3 (q, J 34), 119.4, 123.6 (q, J 284), 125.3, 128.0,
128.7, 129.0, 129.1, 129.4, 129.6, 132.1, 134.8, 136.0, 138.2,
145.6 and 148.1; δF Ϫ75.9 (d, J 7); m/z (CI) 505 (M ϩ Hϩ).
The second component gave compound 11b as a yellow solid
(40 mg, 8%); mp 95–98 ЊC (Found: C, 62.1; H, 5.4; N,
5.3%); [α]2D3 Ϫ116.67 (c 1.2, CHCl3); νmax(KBr)/cmϪ1 1150,
1281 and 1580; δH 1.16 (3 H, d, J 6.7), 1.74 (6 H, s), 4.57 (1
H, q, J 6.7), 4.59 (1 H, d, J 6.9), 5.33 ( 1 H, qd, J 7.2 and
70:30 Diastereomeric mixture of (3S,4S,5R)-4-(2-{(1S)-1-
[isopropyl(methyl)amino]ethyl}phenylsulfonyl)-2-methyl-3-
phenyl-5-(trifluoromethyl)isoxazolidine 14 and (3R,4R,5S)-4-
(2-{(1S)-1-[isopropyl(methyl)amino]ethyl}phenylsulfonyl)-2-
methyl-3-phenyl-5-(trifluoromethyl)isoxazolidine 15. This was
obtained as above from compound 8c (336 mg, 1.00 mmol) and
9a (135 mg, 1.00 mmol) as a yellow oil (273 mg, 58%); Rf 0.60
(2:1 hexane–EtOAc) (Found: C, 59.0; H, 6.4; N, 5.8.
C23H29F3N2O3S requires C, 58.71; H, 6.21; N, 5.95%); νmax
-
(neat)/cmϪ1 1152, 1281 and 2971; δH 0.63 (2.10 H, d, J 6.5), 0.76
(0.90 H, d, J 6.5), 0.86 (2.10 H, d, J 6.5), 0.76 (0.90 H, d, J 6.5),
0.97 (2.10 H, d, J 6.6), 1.14 (0.90 H, d, J 6.5), 1.66 (0.90 H, s),
2.46 (0.30 H, septet, J 6.5), 1.85 (2.10 H, s), 2.63 (0.90 H, s),
2.68 (2.10 H, s), 2.83 (0.70 H, septet, J 6.5), 3.97 (0.30 H, d, J
J. Chem. Soc., Perkin Trans. 1, 1997
1585