HRMS-EI Calc. for C H N O (M), 198.1003. Found: M,
The reaction mixture was warmed to room temperature
9
14
2
3
1
98.1006.
and then partitioned between EtOAc (10 ml) and saturated aq.
potassium sodium tartrate (5 ml). Vigorous stirring was con-
tinued until all the solids dissolved. The organic layer was
2
c. Obtained from 1c in 56% yield as a white solid when
chromatographed (EtOAc–hexane 4:1 v/v), mp 89–92 ЊC;
separated, and dried over MgSO . Evaporation of EtOAc
under reduced pressure gave a residue; this, and N-methyl-
hydroxylamine hydrochloride (323 mg, 3 mmol), were dissolved
4
22
[
α] ϩ23.4 (c 0.1, CHCl ); the major (E-form) isomer in
D
3
1
mixture: H NMR δ 7.83 (br s, 1H), 7.36 (d, 1H, J 7.0 Hz),
5
8
6
.67 (m, 1H), 4.99 (m, 1H), 4.97 (m, 1H), 4.54 (dd, 1H, J 9.0,
.5 Hz), 4.47 (ddd, 1H, J 8.5, 7.0, 6.0 Hz), 4.23 (dd, 1H, J 9.0,
.0 Hz), 3.39 (t, 2H, J 7.4 Hz), 2.21 (m, 1H), 2.19 (m, 1H);
in 90% aq. EtOH (8 ml). NaHCO (378 mg, 4.5 mmol) was
added and the resulting mixture was heated under reflux for
6 h. Removal of EtOH gave a residue, which was extracted with
3
1
3
C NMR δ 158.20 (s, C᎐O), 147.20 (d), 134.39 (d), 117.00 (t),
EtOAc. The combined organic layer was dried over MgSO and
᎐
4
6
5.32 (t), 54.90 (d), 46.75 (t), 34.29 (t). The minor (Z-form)
evaporated under reduced pressure. The residue was purified by
chromatography (EtOAc–EtOH 8:1 v/v) to give products 7a
(129 mg, 70%) and 8a (18 mg, 10%) as white solids. 7a: mp 113–
1
isomer in mixture: H NMR δ 8.15 (br s, 1H), 6.90 (d, 1H, J 5.6
Hz), 5.64 (m, 1H), 5.07 (ddd, 1H, J 9.0, 6.0, 5.6 Hz), 4.97 (m,
2
3
22
1
H), 4.61 (dd, 1H, J 9.0, 8.8 Hz), 4.15 (dd, 1H, J 9.0, 6.0 Hz),
114 ЊC; [α]D Ϫ72.5 (c 0.07, CHCl ); H NMR δ 4.56 (dd, J 9.5,
3
13
.37 (m, 2H), 2.24 (m, 1H), 2.18 (m, 1H); C NMR δ 158.62
8 Hz, 1H), 4.33 (dd, 1H, J 9.5, 2.5 Hz), 4.18 (dd, J 12.0, 9.0 Hz,
1H), 4.16 (dd, 1H, J 9.5, 6.5 Hz), 3.78 (ddd, 1H, J 8.0, 6.5,
2.5 Hz), 3.74 (dd, 1H, J 9.5, 2.0 Hz), 3.51 (dd, 1H, J 9.0,
6.5 Hz), 3.43 (ddddd, 1H, J 9.0, 9.0, 6.5, 6.0, 2.0 Hz), 3.03 (dd,
(
s, C᎐O), 147.83 (d), 134.52 (d), 117.65 (t), 65.80 (t), 51.00
᎐
(
d), 46.23 (t), 33.51 (t); HRMS-EI Calc. for C H N O (M),
8
12
2
3
ϩ
1
84.0847. Found: M 184.0852.
13
J 12.0, 6.0 Hz, 1H), 2.65 (s, 3H); C NMR δ 160.69 (C᎐O),
General procedure for IOOC leading to isoxazolidines 4a–c
78.45 (d), 71.11 (t), 67.27 (t), 60.87 (d), 51.96 (t), 47.93 (d),
ϩ
4
4.82 (q); MS-EI (m/z, %) 184 (M , 20), 140 (68), 98 (13), 85
A mixture of 2a (0.85 g, 50 mmol) and silica gel (60 PF254; 3 g)
was placed on a Pyrex plate with a cover. The Pyrex plate con-
taining the reaction mixture was put in a microwave oven
and irradiated for 12 min as required to complete the reaction.
The mixture was eluted with EtOAc. After removal of EtOAc,
the residue was chromatographed (EtOAc–EtOH 4:1 v/v) to
give 4a (0.7 g, 82%) as a white solid which was identified as
(
100), 84 (87); HRMS-EI Calc. for C H N O (M), 184.0847.
8 12 2 3
ϩ
Found: M , 184.0849. Calc. for C H N O : C, 52.15; H, 6.57;
8
12
2
3
N, 15.21. Found: C, 52.34; H, 6.72; N, 15.17%). 8a: mp 81–
22
1
8
3 ЊC; [α]D ϩ37.6 (c 0.05, CHCl ); H NMR δ 4.65 (ddd, 1H,
3
J 6.0, 4.8, 4.2 Hz), 4.58 (t, 1H, J 9.0 Hz), 4.16 (dd, 1H, J 9.0,
7
4
2
.8 Hz), 3.99 (ddd, 1H, J 9.0, 7.8, 4.8 Hz), 3.73 (dd, 1H, J 13.8,
.8 Hz), 3.22 (dd, 1H, J 13.8, 4.2 Hz), 3.18 (t, J 4.8 Hz, 1H),
7
being consistent with the previously reported compound. Mp
.65 (s, 3H), 2.32 (ddd, 1H, J 12.6, 6.0, 4.8 Hz), 1.88 (d, 1H,
2
3
1
1
11–113 ЊC; [α] Ϫ69.7 (c 0.5, CHCl ); H NMR δ 5.22 (s, 1H),
D
3
13
J 12.6 Hz); C NMR δ 158.88 (C᎐O), 73.46 (d), 66.54 (d), 66.37
4
.58 (dd, 1H, J 9.5, 8.0 Hz), 4.34 (dd, J 9.5, 3.0 Hz, 1H), 4.17
(
(
t), 57.83 (d), 49.96 (t), 47.38 (q), 26.28 (t); MS-EI (m/z, %) 184
(
dd, 1H, J 12.0, 9.0 Hz), 4.00 (dd, 1H, J 9.5, 1.2 Hz), 3.96 (dd,
ϩ
M , 34), 169 (10), 149 (32), 140 (31), 128 (52), 94 (95), 84 (100);
J 9.0, 6.0 Hz, 1H), 3.76 (ddd, 1H, J 8.0, 6.0, 3.0 Hz), 3.51 (dd,
ϩ
HRMS-EI Calc. for C H N O (M); 184.0847. Found: M ,
8
12
2
3
1
2
H, J 9.5, 6.5 Hz), 3.32 (ddddd, J 9.0, 9.0, 7.0, 6.5, 1.2 Hz, 1H),
13
1
84.0852.
.94 (dd, 1H, J 12.0, 7.0 Hz); C NMR δ 160.74 (s, C᎐O), 76.76
(
t), 71.64 (d), 67.46 (t), 63.61 (d), 51.65 (t), 49.43 (d).
7
b. 7b (166 mg, 64%) and 8b (34 mg, 13%) were obtained as
white solids from 3a and N-benzylhydroxylamine hydrochloride
following method A. Chromatography (EtOAc–hexane 2:1 v/v)
4
b. Obtained from 2b in 80% yield as a white solid following
the general procedure when chromatographed (EtOAc–EtOH
:1 v/v), mp 97–99 ЊC; [α]D Ϫ63.2 (c 1.3, CHCl ); H NMR
3
δ 5.19 (s, 1H), 4.53 (t, 1H, J 8.8 Hz), 4.27 (dd, 1H, J 8.8, 3.7
Hz), 3.94 (ddd, 1H, J 8.8, 5.1, 3.7 Hz), 3.79 (dd, 1H, J 12.1, 8.5
Hz), 3.36 (dd, 1H, J 8.8, 5.1 Hz), 3.26 (dd, 1H, J 12.1, 7.0 Hz),
.05 (td, 1H, J 7.0, 8.5 Hz), 1.34 (s, 3H), 1.28 (s, 3H); C NMR
δ 161.14 (s, C᎐O), 81.08 (s), 73.50 (d), 67.25 (t), 65.27 (d),
4.59 (t), 50.11 (d), 29.07 (q), 24.17 (q); HRMS-EI Calc. for
22
1
gave 7b: mp 145–146 ЊC; [α]D Ϫ69.1 (c 0.1, CHCl ); H NMR
23
1
3
4
δ 7.29–7.34 (m, 5H), 4.59 (dd, J 9.2, 8.0 Hz, 1H), 4.35 (d, 1H,
J 11.5 Hz), 4.36 (dd, 1H, J 9.2, 2.5 Hz), 4.21 (dd, 1H, J 12.0,
9
3
3
2
1
6
.0 Hz), 4.15 (dd, 1H, J 9.5, 7.0 Hz), 3.73 (d, 1H, J 11.5 Hz),
.79 (ddd, 1H, J 8.0, 6.5, 2.5 Hz), 3.75 (dd, J 9.5, 2.0 Hz, 1H),
.54 (dd, 1H, J 9.0, 6.5 Hz), 3.44 (ddddd, 1H, J 9.0, 9.0, 7.0, 6.0,
.0 Hz), 3.07 (dd, 1H, J 12.0, 6.0 Hz); C NMR δ 160.42 (C᎐O),
35.48 (s), 129.25 (d), 128.75 (d), 128.17 (d), 77.54 (d), 71.01 (t),
13
3
᎐
13
5
ϩ
C H N O (M), 198.1003. Found: M , 198.0998. Calc. for
9
14
2
3
6.35 (t), 62.54 (t), 61.87 (d), 49.96 (t), 47.91 (d); MS-EI
C H N O : C, 54.52; H, 7.12; N, 14.14. Found: C, 54.762;
9
14
2
3
ϩ
(
m/z, %) 260 (M , 24), 140 (56), 91 (21), 85 (100), 84 (83);
H, 7.34; N, 14.17%.
ϩ
HRMS-EI Calc. for C H N O (M), 260.1160. Found: M ,
14
16
2
3
2
60.1164. Calc. for C H N O : C, 64.59; H, 6.20; N, 10.77.
14 16 2 3
4
c. Obtained from 2c in 77% yield as a white solid following
Found: C, 64.47; H, 6.09; N, 10.72%. 8b: mp 105–107 ЊC;
the general procedure when chromatographed (EtOAc–EtOH
:1 v/v), mp 75–76 ЊC; [α]D Ϫ31.3 (c 0.7, CHCl ); H NMR
3
δ 5.20 (s, 1H), 4.57 (dd, 1H, J 9.0, 8.0 Hz), 4.29 (dd, 1H, J 9.0,
.1 Hz), 4.05 (dd, 1H, J 9.5, 1.5 Hz), 3.89 (ddd, 1H, J 8.8, 8.0,
.1 Hz), 3.82 (dd, 1H, J 8.8, 4.8 Hz), 3.75 (ddd, 1H, J 13.6, 11.5,
.8 Hz), 3.57 (dd, 1H, J 9.5, 7.0 Hz), 3.20 (ddd, 1H, J 13.6, 4.8,
.2 Hz), 3.11 (ddddd, J 7.0, 4.8, 4.8, 4.2, 1.5 Hz, 1H), 2.08
m, 1H), 1.74 (m, 1H); C NMR δ 161.31 (s, C᎐O), 74.56 (t),
2.97 (d), 66.52 (t), 62.74 (d), 48.46 (d), 40.18 (t), 31.02 (t);
2
2
1
[
α] ϩ34.5 (c 0.04, CHCl ); H NMR δ 7.30–7.33 (m, 5H), 4.51
23
1
D
3
4
(
ddd, J 6.0, 5.0, 4.2 Hz, 1H), 4.38 (t, 1H, J 9.0 Hz), 4.32 (d, 1H,
J 12.0 Hz), 4.02 (dd, 1H, J 9.0, 7.5 Hz), 3.84 (ddd, 1H, J 9.0,
.5, 4.8 Hz), 3.75 (d, 1H, J 12.0 Hz), 3.64 (dd, 1H, J 13.6, 5.0
Hz), 3.16 (dd, J 13.6, 4.2 Hz, 1H), 3.11 (dd, 1H, J 5.0, 4.8 Hz),
7
7
4
4
(
7
7
13
2
,25 (ddd, 1H, J 12.6, 6.0, 5.0 Hz), 1.86 (d, J 12.6 Hz, 1H);
C
NMR δ 159.12 (C᎐O), 135.23 (s), 129.21 (d), 128.87 (d), 128.31
13
᎐
(
d), 72.98 (d), 66.46 (d), 66.18 (t), 62.47 (t), 58.03 (d), 50.06 (t),
ϩ
2
1
7.12 (t); MS-EI (m/z, %) 260 (M , 30), 204 (52), 169 (11),
ϩ
HRMS-EI Calc. for C H N O (M), 184.0847. Found: M ,
84.0848.
8
12
2
3
49 (28), 140 (34), 94 (89), 84 (100); HRMS-EI Calc. for
1
ϩ
C H N O (M), 260.1160. Found: M , 260.1157.
14
16
2
3
General procedure for reduction of 1a and INC leading to
isoxazolidines 7a,b and 8a,b
Method B. To a solution of 1a (185 mg, 1 mmol) in dry
CH Cl2 (7 ml) at Ϫ78 ЊC under nitrogen was added drop-
2
Method A. To a solution of 1a (185 mg, 1 mmol) in dry
CH Cl (7 ml) at Ϫ78 ЊC under nitrogen was added dropwise
DIBAL-H (1.0 M in hexane; 1.6 ml). After stirring of the
wise DIBAL-H (1.0 M in hexane; 1.6 ml). After stirring of the
mixture for 2 h at Ϫ78 ЊC, MeOH (0.5 ml) was added.
The reaction mixture was warmed to room temperature and
then partitioned between EtOAc (10 ml) and saturated aq.
2
2
mixture for 2 h at Ϫ78 ЊC, MeOH (0.5 ml) was added.
J. Chem. Soc., Perkin Trans. 1, 2001, 452–456
455