PAPER
High Stereoselectivity of the Tandem Sequence Diels–Alder Reaction/Ireland–Claisen Rearrangement
2385
40.7 [C(2.7a)], 39.6 [C(2)], 38.9 [C(2.3a)], 30.7 [C(2.5)], 19.8
[C(2.4)].
(vw), 719 (w), 678 (w), 631 (w), 621 (m), 581 (m), 567 (m), 534
(m), 511 (w), 456 (vw), 437 cm–1 (vw).
MS (DCI): m/z (%) = 299 (9) [M]+, 239 (9), 92 (38), 91 (35), 79
(17), 77 (24), 74 (100), 44 (13).
1H NMR (400 MHz, CDCl3): d = 7.52–7.47 [m, 2 H, HPh-C(2.2III)],
7.43–7.38 [m, 1 H, HPh-C(2.2IV)], 7.33–7.30 [m, 2 H, HPh-C(2.2II)],
6.25 [dt, 3J(2.7,2.6) = 10.3 Hz, 3J(2.7,2.7a) ≈ 4J(2.7,2.5) ≈ 2.0 Hz, 1
H, H-C(2.7)], 6.02 [dt, 3J(2.6,2.7) = 10.3 Hz, 3J(2.6,2.5) ≈
4J(2.6,2.7a) ≈ 3.1 Hz, 1 H, H-C(2.6)], 3.62 [s, 3 H, H3-C(1¢)], 3.50
[dq,3J(2.7a,2.3a) = 8.8 Hz, 3J(2.7a,2.7) ≈ 4J(2.7a,2.6) ≈ 5J(2.7a,2.5) ≈
3.1 Hz, 1 H, H-C(2.7a)], 3.26 [ddd, 3J(2.3a,Ha-2.4) = 12.0 Hz,
Anal. Calcd for C17H17NO4 (299.32): C, 68.22; H, 5.72; N, 4.68.
Found: C, 68.21; H, 5.89; N, 4.45.
Methyl 2-(1,3-Dioxo-2-phenyl-2,3,3a,4,5,7a-hexahydro-1H-
isoindol-5-yl)propanoate (3b)
3
3J(2.3a,2.7a) = 8.8 Hz, J(2.3a,Hb-2.4) = 6.1 Hz, 1 H, H-C(2.3a)],
Using N-phenylmaleimide (349.6 mg, 2.02 mmol) and 2b (766.5
mg, 3.19 mmol) according to the general procedure, with purifica-
tion by flash chromatography (CH2Cl2–Et2O–hexane, 7:1:2) gave a
colorless oil that crystallized (CH2Cl2–hexane) to give pure 3b as a
white powder; yield: 486.9 mg (77%); mp 102–102.5 °C; Rf
(CH2Cl2–Et2O–hexane, 7:1:2) = 0.29.
2.64–2.58 [m, 1 H, H-C(2.5)], 2.34–2.28 [m, 1 H, Hb-C(2.4)], 2.29
[d, 3J(2,2.5) = 3.4 Hz, 1 H, H-C(2)], 1.53 [dt*, 2J(Ha-2.4,Hb-2.4) ≈
3
3
12.2 Hz, J(Ha-2.4,2.3a) ≈ J(Ha-2.4,2.5) ≈ 11.2 Hz, 1 H, Ha-
C(2.4)], 1.08 [s, 9 H, C(CH3)3].
13C NMR (100 MHz, CDCl3): d = 177.87 [C(2.1)], 175.52 [C(2.3)],
173.38 [C(1)], 133.80 [C(2.6)], 131.68 [CPh(2.2I)], 129.10
[CPh(2.2III)], 128.54 [CPh(2.2IV)], 126.32 [CPh(2.2II)], 120.51
[C(2.7)], 58.95 [C(2)], 51.00 C(1¢)], 40.38 [C(2.7a)], 39.47
[C(2.3a)], 33.64 [C(3)], 32.89 [C(2.5)], 31.66 [C(2.4)], 28.18
[C(3¢)].
IR: 3055 (vw), 3023 (vw), 2986 (vw), 2960 (vw), 2907 (vw), 2875
(vw), 1775 (vw), 1708 (s), 1644 (vw), 1600 (vw), 1503 (w), 1458
(vw), 1437 (vw), 1384 (m), 1355 (w), 1302 (vw), 1284 (vw), 1274
(vw), 1253 (vw), 1228 (w), 1197 (m), 1180 (m), 1170 (w), 1149
(w), 1138 (w), 1123 (vw), 1069 (vw), 1055 (vw), 1033 (vw), 991
(vw), 824 (vw), 753 (w), 709 (w), 700 (w), 692 (vw), 586 cm–1 (vw).
MS (ESI): m/z = 378.3 [M + Na]+.
1H NMR (400 MHz, CDCl3): d = 7.49–7.45 [m, 2 H, HPh-C(2.2III)],
7.41–7.37 [m, 1 H, HPh-C(2.2IV)], 7.29–7.26 [m, 2 H, HPh.-C(2.2II)],
6.07 [ddd, 3J(2.7,2.6) = 10.1 Hz, 3J(2.7,2.7a) = 3.6 Hz,
4J(2.7,2.5) = 2.5 Hz, 1 H, H-C(2.7)], 5.89 [dt, 3J(2.6,2.7) = 10.1 Hz,
3J(2.6,2.5) ≈ 4J(2.6,2.7a) = 2.1 Hz, 1 H, H-C(2.6)], 3.70 [s, 3 H, H-
C(1¢)], 3.52 [dq, 3J(2.7a,2.3a) = 8.3 Hz, 3J(2.7a,2.7) ≈ 4J(2.7a,2.6) ≈
5J(2.7a,2.5) = 3.2 Hz, 1 H, H-C(2.7a)], 3.19 [ddd, 3J(2.3a,Ha-
HRMS: m/z [M + Na]+ calcd for C21H25NNaO4: 378.16758; found:
378.16763.
Methyl (1,3-Dioxo-2-phenyl-2,3,3a,4,5,7a-hexahydro-1H-iso-
indol-5-yl)(methoxy)acetate (3d)
Using N-phenylmaleimide (350.6 mg, 2.02 mmol) and 2d (758.6
mg, 2.96 mmol) according to the general procedure, with purifica-
tion by flash chromatography (CH2Cl2–Et2O–hexane, 7:1:2) gave
an colorless oil that crystallized (CH2Cl2–hexane) to give pure 3d as
a white powder; yield: 441.6 mg (66%); mp 124.5 °C; Rf (CH2Cl2–
Et2O–hexane, 7:1:2) = 0.20.
3
2.4) = 11.5 Hz, 3J(2.3a,2.7a) = 8.6 Hz, J(2.3a,Hb-2.4) = 6.0 Hz, 1
H, H-C(2.3a)], 2.60–2.53 [m, 1 H, H-C(2.5)], 2.48 [quint,
3J(2,3) = 3J(2,2.5) = 7.1 Hz, 1 H, H-C(2)], 2.27 [ddd, 2J(Hb-2.4,Ha-
3
3
2.4) = 12.8 Hz, J(Hb-2.4,2.3a) = 5.5 Hz, J(Hb-2.4,2.5) = 4.5 Hz,
2
3
1 H, Hb-C(2.4)], 1.41 [ddd, J(Ha-2.4,Hb-2.4) = 12.7 Hz, J(Ha-
2.4,2.3a) = 11.5 Hz, 3J(Ha-2.4,2.5) = 10.1 Hz, 1 H, Ha-C(2.4)],
1.18 [d, 3J(3,2) = 7.0 Hz, 3 H, H-C(3)].
IR: 3067 (vw), 3044 (vw), 3009 (vw), 2963 (vw), 2936 (vw), 2882
(vw), 2860 (vw), 2830 (vw), 1733 (s), 1709 (s), 1597 (vw), 1501
(w), 1454 (w), 1444 (vw), 1391 (m), 1341 (vw), 1325 (w), 1302 (w),
1289 (w), 1274 (m), 1243 (w), 1230 (w), 1202 (m), 1186 (m), 1165
(w), 1117 (m), 1082 (w), 1031 (vw), 1055 (vw), 1014 (w), 988 (vw),
976 (w), 824 (w), 756 (w), 694 (m), 581 (w), 493 cm–1 (vw).
13C NMR (100 MHz, CDCl3): d = 178.0 [C(2.1)], 175.5 [C(2.3)],
175.3 C((1)], 133.7 [C(2.6)], 131.7 [CPh(2.2I)], 129.1 [CPh(2.2III)],
128.6 [CPh(2.2IV)], 126.4 [CPh(2.2II)], 121.5 [C(2.7)], 51.8 [C(1¢)],
43.4 [C(2)], 40.8 [C(2.7a)], 39.0 [C(2.3a)], 36.6 [C(2.5)], 26.7
[C(2.4)],13.7 [C(3)].
MS (DCI): m/z (%) = 314 (32) [M + 1]+, 313 (39) [M]+, 282 (32),
254 (37), 253 (100), 119 (14), 107 (18), 106 (51), 105 (22), 91 (43),
88 (80), 79 (58), 78 (13), 77 (40), 57 (12).
1H NMR (400 MHz, CDCl3): d = 7.48–7.42 [m, 2 H, HPh-C(2.2III)],
7.39–7.35 [m, 1 H, HPh-C(2.2IV)], 7.27–7.25 [m, 2 H, HPh-C(2.2II)],
6.12 [ddd, 3J(2.7,2.6) = 10.0 Hz, 3J(2.7,2.7a) = 3.7 Hz,
4J(2.7,2.5) = 2.7 Hz, 1 H, H-C(2.7)], 5.92 [dt, 3J(2.6,2.7) = 10.1 Hz,
3J(2.6,2.5) ≈ 4J(2.6,2.7a) = 2.3 Hz, 1 H, H-C(2.6)], 3.78 [s, 3 H, H-
C(2¢)], 3.75 [d, 3J(2,2.5) = 5.3 Hz, 1 H, H-C(2)], 3.50 [dq,
3J(2.7a,2.3a) = 8.7 Hz, 3J(2.7a,2.7) ≈ 4J(2.7a,2.6) ≈ 5J(2.7a,2.5) = 2.9
Anal. Calcd for C18H19NO4 (313.35): C, 69.00; H 6.11; N 4.47.
Found: C, 69.26; H, 6.18; N, 4.38.
3
Hz, 1 H, H-C(2.7a)], 3.38 [s, 3 H, H-C(1¢)], 3.15 [ddd, J(2.3a,Ha-
2.4) = 11.2 Hz, 3J(2.3a,2.7a) = 8.6 Hz, 3J(2.3a,Hb-2.4) = 6.3 Hz, 1 H,
H-C(2.3a)], 2.70–2.64 [m, 1 H, H-C(2.5)], 2.20 [ddd, 2J(Hb-2.4,Ha-
2.4) = 13.2 Hz, 3J(Hb-2.4,2.3a) = 6.3 Hz, 3J(Hb-2.4,2.5) = 4.4 Hz, 1
H, Hb-C(2.4)], 1.67 [ddd, 2J(Ha-2.4,Hb-2.4) = 13.2 Hz, 3J(Ha-
2.4,2.3a) = 11.1 Hz, 3J(Ha-2.4,2.5) = 9.9 Hz, 1 H, Ha-C(2.4)].
Methyl 2-(1,3-Dioxo-2-phenyl-2,3,3a,4,5,7a-hexahydro-1H-
isoindol-5-yl)-3,3-dimethylbutanoate (3c)
Using N-phenylmaleimide (250 mg, 1.44 mmol) and 2c (100 mg,
0.35 mmol) according to the general procedure, with purification by
flash chromatography (CH2Cl2) gave a colorless oil that was crys-
tallized (CH2Cl2–hexane) to give pure 3c as a white powder; yield:
66 mg (53%); mp 164–166 °C; Rf (hexane–EtOAc, 98:2) = 0.83.
Monocrystals were obtained by recrystallization (CH2Cl2–hexane).
13C NMR (100 MHz, CDCl3): d = 177.7 [C(2.3)], 175.3 [C(2.1)],
171.5 [C(1)], 131.7 [CPh.(2.2I)], 131.2 [C(2.6)], 129.1 [CPh(2.2III)],
128.5 [CPh(2.2IV)], 126.3 [CPh(2.2II)], 122.5 [C(2.7)], 82.6 [C(2)],
58.8 [C(2¢)], 52.1 [C(1¢)], 40.6 [C(2.7a)], 38.6 [C(2.3a)], 37.3
[C(2.5)], 24.9 [C(2.4)].
MS (DCI): m/z (%) = 329 (8) [M]+, 297 (31), 270 (29), 265 (21), 226
(35), 120 (11), 119 (15), 118 (10), 105 (11), 104 (58), 103 (60), 92
(14), 91 (100), 89 (34), 79 (89), 78 (15), 77 (59), 75 (45), 65 (12),
45 (11).
IR: 3100 (vw), 3070 (vw), 3049 (w), 2989 (m), 2962 (s), 2921 (m),
2907 (m), 2866 (m), 2554 (vw), 2336 (vw), 1974 (vw), 1899 (vw),
1778 (m), 1708 (vs), 1593 (m), 1491 (s), 1468 (m), 1452 (m), 1468
(m), 1440 (m), 1434 (m), 1397 (s), 1376 (vs), 1271 (s), 1249 (m),
1230 (m), 1215 (s), 1179 (vs), 1168 (s), 1148 (vs), 1137 (s), 1090
(m), 1077 (m), 1065 (m), 1023 (w), 992 (m), 978 (m), 942 (m), 922
(vw), 903 (w), 849 (w), 819 (m), 810 (m), 780 (w), 757 (s), 732
Anal. Calcd for C18H19NO5 (329.35): C, 65.64; H, 5.81; N, 4.25.
Found: C, 65.39; H, 5.95; N, 4.27.
Synthesis 2007, No. 15, 2379–2387 © Thieme Stuttgart · New York