The Journal of Organic Chemistry
Article
7.30 (q, 4H, J = 8.0 Hz), 7.25 (t, 3H, J = 8.4 Hz), 6.99 (t, 1H, J = 7.2
Hz), 4.08−3.98 (m, 2H), 3.96−3.83 (m, 2H), 3.44 (d, 1H, J = 12.8
Hz), 3.14 (d, 1H, J = 12.4 Hz), 1.73 (s, 3H), 1.03 (t, 3H, J = 7.2 Hz),
0.95 (t, 3H, J = 7.2 Hz) ppm; 13C{1H} NMR (CDCl3, 100 MHz) δ
168.3, 168.2, 147.0, 144.1, 128.2, 128.1, 127.1, 125.0, 123.0, 117.4,
81.9, 78.7, 62.1, 61.8, 52.3, 27.1, 13.7, 13.6 ppm. HRMS (ESI) m/z
[M + H]+ Calcd for C22H26NO5 384.1805, found 384.1807.
129.1, 128.7, 128.2, 127.4, 124.9, 119.7, 81.8, 81.1, 63.1, 62.4, 62.1,
61.5, 14.0, 13.7, 13.4 ppm. HRMS (ESI) m/z [M + H]+ Calcd for
C24H28NO7 442.1860, found 442.1861.
Diethyl-4,6-dioxo-2-phenyltetrahydrofuro[3,4-d]isoxazole-
3,3(2H)-dicarboxylate (4af). Yellow oil (84% yield, 61.0 mg); TLC,
1
Rf = 0.3 (PE/EtOAc = 10:1, v/v); H NMR (CDCl3, 400 MHz) δ
7.42 (d, 2H, J = 8.4 Hz), 7.28 (t, 2H, J = 8.0 Hz), 7.13 (t, 1H, J = 6.8
Hz), 5.31 (d, 1H, J = 8.0 Hz), 4.61 (d, 1H, J = 7.6 Hz), 4.28−4.17 (m,
1H), 3.98−3.90 (m, 1H), 3.75−3.67 (m, 1H), 3.92−3.84 (m, 1H),
1.20 (t, 3H, J = 7.2 Hz), 0.86 (t, 3H, J = 7.2 Hz) ppm; 13C{1H} NMR
(CDCl3, 100 MHz) δ 171.3, 166.0, 165.4, 145.7, 128.3, 125.9, 120.3,
80.4, 62.9, 62.7, 58.8, 13.5, 13.3 ppm. HRMS (ESI) m/z [M + H]+
Calcd for C17H18NO8 364.1027, found 364.1030.
Diethyl-4,6-dioxo-2,5-diphenyltetrahydro-2H-pyrrolo[3,4-d]-
isoxazole-3,3(3aH)-dicarboxylate (4ag). Yellow oil (80% yield, 70.1
mg); TLC, Rf = 0.3 (PE/EtOAc = 10:1, v/v); 1H NMR (CDCl3, 400
MHz) δ 7.50 (t, 2H, J = 7.6 Hz), 7.43 (d, 1H, J = 7.2 Hz), 7.41 (d,
2H, J = 8.0 Hz), 7.33 (d, 2H, J = 8.0 Hz), 7.30 (t, 2H, J = 7.6 Hz),
7.18 (t, 1H, J = 7.2 Hz), 5.19 (d, 1H, J = 7.6 Hz), 4.59 (d, 1H, J = 7.6
Hz), 4.32 (q, 2H, J = 6.8 Hz), 4.10−4.02 (m, 1H), 3.87−3.79 (m,
1H), 1.30 (t, 3H, J = 7.2 Hz), 0.86 (t, 3H, J = 7.2 Hz) ppm; 13C{1H}
NMR (CDCl3, 100 MHz) δ 172.7, 172.0, 164.7, 164.6, 144.7, 131.2,
129.3, 129.1, 128.2, 126.5, 126.0, 120.6, 80.8, 74.5, 63.0, 62.3, 55.0,
13.8, 13.3 ppm. HRMS (ESI) m/z [M + H]+ Calcd for C23H23N2O7
439.1500, found 439.1500.
Diethyl 2-Phenyloctahydrocycloocta[d]isoxazole-3,3(2H)-dicar-
boxylate (4ah). Yellow oil (93% yield, 69.8 mg); TLC, Rf = 0.3
(PE/EtOAc = 20:1, v/v); 1H NMR (CDCl3, 400 MHz) δ 7.21 (d, J =
8.4 Hz, 2H), 7.14 (t, J = 8.0 Hz, 2H), 6.95 (d, J = 7.2 Hz, 1H), 4.43
(t, J = 8.8 Hz, 1H), 4.18−4.01 (m, 1H), 4.05−3.99 (m, 1H), 3.96−
3.84 (m, 2H), 3.00 (t, J = 9.6 Hz, 1H), 1.90 (q, J = 12.4 Hz, 2H), 1.82
(d, J = 14.4 Hz, 1H), 1.75−1.64 (m, 2H), 1.61−1.49 (m, 3H), 1.37−
1.26 (m, 3H), 1.19−1.14 (m, 1H), 1.10 (t, J = 7.2 Hz, 3H), 0.94 (t, J
= 7.2 Hz, 3H) ppm; 13C{1H} NMR (CDCl3, 100 MHz) δ 168.0,
166.1, 146.9, 128.0, 124.0, 119.3, 82.6, 80.9, 61.7, 61.1, 54.8, 29.8,
27.8, 27.4, 25.6, 25.5, 23.3, 13.8, 13.7 ppm. HRMS (ESI) m/z [M +
H]+ Calcd for C21H30NO5 376.2118, found 376.2131.
Diethyl 5-Formyl-5-methyl-2-phenylisoxazolidine-3,3-dicarboxy-
late (4z). Colorless oil (91% yield, 61.0 mg); TLC, Rf = 0.3 (PE/
1
EtOAc = 20:1, v/v); H NMR (CDCl3, 400 MHz) δ 9.70 (s, 1H),
7.40 (d, 2H, J = 8.0 Hz), 7.29 (t, 2H, J = 6.4 Hz), 7.13 (t, 1H, J = 7.2
Hz), 4.26 (qd, 2H, J = 7.2, 2.8 Hz), 3.94−3.85 (m, 1H), 3.75−3.67
(m, 1H), 3.17 (d, 1H, J = 13.2 Hz), 3.02 (d, 1H, J = 12.8 Hz), 1.51 (s,
3H), 1.29 (t, 3H, J = 7.2 Hz), 0.84 (t, 3H, J = 7.2 Hz) ppm; 13C{1H}
NMR (CDCl3, 100 MHz) δ 203.3, 168.0, 166.6, 145.8, 128.2, 125.0,
119.6, 83.9, 77.8, 62.1, 61.9, 45.8, 17.4, 13.9, 13.4 ppm. HRMS (ESI)
m/z [M + H]+ Calcd for C17H22NO6 336.1442, found 336.1447.
Triethyl 2,5-Diphenylisoxazolidine-3,3,5-tricarboxylate (4aa).
Yellow oil (90% yield, 79.4 mg); TLC, Rf = 0.3 (PE/EtOAc = 20:1,
1
v/v); H NMR (CDCl3, 600 MHz) δ 7.54 (d, 2H, J = 6.6 Hz), 7.45
(dd, 2H, J = 8.4, 1.2 Hz), 7.39 (t, 2H, J = 13.8 Hz), 7.35 (d, 1H, J =
7.2 Hz), 7.27 (t, 2H, J = 8.4 Hz), 7.08 (t, 1H, J = 7.2 Hz), 4.28 (q,
2H, J = 7.2 Hz), 4.27−4.23 (m, 1H), 4.19−4.14 (m, 1H), 3.96 (d,
1H, J = 7.2 Hz), 3.88−3.82 (m, 1H), 3.73−3.67 (m, 1H), 3.32 (d,
1H, J = 12.6 Hz), 1.29 (t, 3H, J = 7.2 Hz), 1.20 (t, 3H, J = 7.2 Hz),
0.84 (t, 3H, J = 7.2 Hz) ppm; 13C{1H} NMR (CDCl3, 150 MHz) δ
171.6, 168.1, 166.9, 146.1, 136.7, 128.4, 128.0, 125.3, 124.4, 119.4,
85.0, 77.9, 62.0, 61.9, 48.7, 13.9, 13.8, 13.3 ppm. HRMS (ESI) m/z
[M + H]+ Calcd for C24H28NO7 442.1860, found 442.1864.
3,3-Diethyl 4,5-Dimethyl-2-phenylisoxazolidine-3,3,4,5-tetracar-
boxylate (4ab). Yellow oil (90% yield, 73.6 mg), TLC, Rf = 0.3 (PE/
1
EtOAc = 5:1, v/v); H NMR (CDCl3, 400 MHz) δ 7.37 (d, 2H, J =
8.4 Hz), 7.18 (t, 2H, J = 8.0 Hz), 7.01 (t, 1H, J = 7.2 Hz), 5.16 (d,
1H, J = 7.6 Hz), 4.47 (d, 1H, J = 7.6 Hz), 4.10 (q, 2H, J = 7.2 Hz),
3.95−3.87 (m, 1H), 3.78−3.73 (m, 1H), 3.71 (s, 3H), 3.65 (s, 3H),
1.14 (t, 3H, J = 7.2 Hz), 0.86 (t, 3H, J = 7.2 Hz) ppm; 13C{1H} NMR
(CDCl3, 100 MHz) δ 168.1, 168.0, 166.0, 165.7, 146.4, 128.2, 125.0,
119.5, 80.1, 76.7, 62.6, 62.3, 58.5, 52.6, 52.6, 13.7, 13.3 ppm. HRMS
(ESI) m/z [M + H]+ Calcd for C19H24NO9 410.1446, found
410.1434.
Diethyl 2-Phenyltetrahydrofuro[2,3-d]isoxazole-3,3(2H)-dicar-
boxylate (4ai). Colorless oil (92% yield, 61.7 mg); TLC, Rf = 0.3
1
(PE/EtOAc = 20:1, v/v); H NMR (CDCl3, 600 MHz) δ 7.42 (d,
2H, J = 7.6 Hz), 7.23 (t, 2H, J = 8.4 Hz), 7.09 (t, 1H, J = 7.2 Hz),
5.96 (d, 1H, J = 5.4 Hz), 4.36−4.31 (m, 1H), 4.29−4.21 (m, 2H),
3.98 (td, 1H, J = 7.6, 2.4 Hz), 3.90−3.86 (m, 2H), 3.67−3.62 (m,
1H), 2.14−2.06 (m, 1H), 1.94−1.90 (m, 1H), 1.28 (t, 3H, J = 7.2
Hz), 0.76 (t, 3H, J = 7.2 Hz) ppm; 13C{1H} NMR (CDCl3, 150
MHz) δ 166.6, 165.7, 146.1, 127.9, 125.3, 120.8, 104.2, 82.4, 69.0,
61.8, 61.4, 54.0, 28.9, 13.9, 13.2 ppm. HRMS (ESI) m/z [M + H]+
Calcd for C17H22NO6 336.1442, found 336.1438.
Triethyl 5-(6-Chloro-9H-purin-9-yl)-2-phenylisoxazolidine-3,3,4-
tricarboxylate (4aj). Yellow oil (86% yield, 86.5 mg); TLC, Rf = 0.3
(PE/EtOAc = 2:1, v/v); 1H NMR (CDCl3, 600 MHz) δ 8.78 (s, 1H),
8.76 (s, 1H), 7.26 (t, 2H, J = 6.6 Hz), 7.24−7.21 (m, 2H), 7.16 (d,
1H, J = 7.2 Hz), 7.13 (t, 1H, J = 7.2 Hz), 4.80 (d, 1H, J = 4.8 Hz),
4.40−4.32 (m, 2H), 4.00 (dd, 1H, J = 7.2, 3.6 Hz), 3.92 (dd, 1H, J =
7.2, 3.6 Hz), 3.75 (s, 3H), 1.27 (t, 3H, J = 7.2 Hz), 0.94 (t, 3H, J = 7.2
Hz) ppm; 13C{1H} NMR (CDCl3, 150 MHz) δ 166.8, 165.7, 164.2,
151.6, 151.1, 144.5, 143.8, 128.4, 125.8, 119.4, 81.4, 80.0, 63.2, 62.3,
62.2, 53.0, 13.8, 13.7, 13.3 ppm. HRMS (ESI) m/z [M + H]+ Calcd
for C22ClH23N5O7 504.1281, found 504.1288.
Triethyl 5-(6-Methoxy-9H-purin-9-yl)-2-phenylisoxazolidine-
3,3,4-tricarboxylate (4ak). Yellow oil (94% yield, 96.5 mg); TLC,
Rf = 0.3 (PE/EtOAc = 2:1, v/v); 1H NMR (CDCl3, 600 MHz) δ 8.55
(s, 1H), 8.52 (s, 1H), 7.24 (d, 2H, J = 1.2 Hz), 7.23 (s, 2H), 7.09 (d,
2H, J = 4.8 Hz), 4.79 (d, 1H, J = 4.8 Hz), 4.34−4.28 (m, 2H), 4.21−
4.16 (m, 2H), 4.15 (s, 3H), 4.04−3.95 (m, 1H), 3.97−3.91 (m, 1H),
1.25 (t, 3H, J = 7.2 Hz), 1.20 (t, 3H, J = 7.2 Hz), 0.95 (t, 3H, J = 7.2
Hz) ppm; 13C{1H} NMR (CDCl3, 150 MHz) δ 166.4, 165.9, 164.3,
161.0, 152.5, 151.9, 144.9, 140.6, 128.3, 125.5, 121.1, 119.3, 81.2,
80.0, 63.0, 62.2, 62.1, 54.2, 13.7, 13.7, 13.4 ppm. HRMS (ESI) m/z
[M + H]+ Calcd for C24H28N5O8 514.1932, found 514.1930.
3,3-Diethyl-4,5-dimethyl-2-phenylisoxazolidine-3,3,4,5-tetracar-
boxylate (4ac). Yellow oil (95% yield, 77.7 mg); TLC, Rf = 0.3 (PE/
1
EtOAc = 5:1, v/v); H NMR (CDCl3, 400 MHz) δ 7.22 (t, 2H, J =
7.6 Hz), 7.18 (t, 2H, J = 7.6 Hz), 7.02 (t, 1H, J = 7.2 Hz), 5.08 (d,
1H, J = 6.4 Hz), 4.51 (d, 1H, J = 6.8 Hz), 4.17−4.09 (m, 1H), 4.06−
4.00 (m, 1H), 3.92 (q, 2H, J = 7.2 Hz), 3.76 (s, 3H), 3.69 (s, 3H),
1.07 (t, J = 7.2 Hz, 3H), 0.95 (t, 3H, J = 7.2 Hz) ppm; 13C{1H} NMR
(CDCl3, 100 MHz) δ 168.1, 167.4, 164.2, 144.7, 127.2, 124.0, 118.3,
78.9, 75.2, 61.7, 61.2, 57.6, 51.9, 51.7, 12.6, 12.5 ppm. HRMS (ESI)
m/z [M + H]+ Calcd for C19H24NO9 410.1446, found 410.1434.
Diethyl 4-Benzoyl-2,5-diphenylisoxazolidine-3,3-dicarboxylate
(4ad). White solid (96% yield, 90.9 mg); mp 144−145 °C; TLC,
1
Rf = 0.3 (PE/EtOAc = 20:1, v/v); H NMR (CDCl3, 400 MHz) δ
7.70 (d, 2H, J = 7.6 Hz), 7.49 (d, 2H, J = 7.6 Hz), 7.44 (dd, 2H, J =
7.2, 1.2 Hz), 7.41 (t, 1H, J = 7.6 Hz), 7.27 (t, 2H, J = 7.6 Hz), 7.22 (t,
4H, J = 7.2 Hz), 7.18 (d, 1H, J = 4.0 Hz), 7.05 (t, 1H, J = 7.2 Hz),
5.47 (s, 2H), 4.05−3.96 (m, 1H), 3.86−3.77 (m, 2H), 3.53−3.45 (m,
1H), 0.78 (t, 3H, J = 7.2 Hz), 0.70 (t, 3H, J = 7.2 Hz) ppm; 13C{1H}
NMR (CDCl3, 100 MHz) δ 196.4, 166.6, 166.5, 146.2, 137.1, 135.6,
133.7, 129.1, 128.8, 128.6, 128.6, 128.2, 127.4, 125.7, 121.0, 83.3,
82.5, 62.8, 62.3, 61.8, 13.3, 13.2 ppm. HRMS (ESI) m/z [M + H]+
Calcd for C28H28NO6 474.1911, found 474.1913.
Triethyl 2,5-Diphenylisoxazolidine-3,3,4-tricarboxylate (4ae).
Yellow oil (80% yield, 70.6 mg), TLC, Rf = 0.3 (PE/EtOAc = 20:1,
v/v); 1H NMR (CDCl3, 400 MHz) δ 7.57 (dd, 2H, J = 7.6, 1.2 Hz),
7.39 (dd, 5H, J = 18.0, 7.6 Hz), 7.27 (t, 2H, J = 8.4 Hz), 7.09 (t, 1H, J
= 7.6 Hz), 5.42 (d, 1H, J = 8.8 Hz), 4.38 (d, 1H, J = 9.2 Hz), 4.31−
4.23 (m, 1H), 4.17−4.09 (m, 3H), 4.04−3.96 (m, 1H), 3.83−3.75
(m, 1H), 1.19 (td, 6H, J = 7.2, 2.4 Hz), 0.95 (t, 3H, J = 7.2 Hz) ppm;
13C{1H} NMR (CDCl3, 100 MHz) δ 168.8, 166.4, 146.4, 136.0,
H
J. Org. Chem. XXXX, XXX, XXX−XXX