PAPER
Syntheses of Pyrroloisoindolones
1357
1H NMR (CDCl3, 250 MHz): d = 3.90 (s, 3 H, OCH3), 5.95 (d,
J = 3.6 Hz, 1 H, 2-H), 6.90 (d, J = 3.6 Hz, 1 H, 3-H), 6.99–7.73 (m,
4 H, Ar).
the aqueous layer was extracted with CH2Cl2 (2 × 10 mL) and
worked up to yield the product.
3-(1-Methoxy-2-oxopropylidene)-2,3-dihydro-1H-isoindol-1-
one (14a)
According to the general procedure, treatment of 7a (300 mg, 1.38
mmol) with 2 N H2SO4 (0.5 mL) in THF (10 mL) yielded after pu-
rification by column chromatography (CH2Cl2–MeOH, 98:2) 205
mg (68%) of 14a as pale yellow solid, as a 89:11 mixture of Z/E
diastereomers (determined by 1H NMR spectroscopy); mp 155 °C.
13C NMR (CDCl3, 62.9 MHz): d = 58.7 (q, OCH3), 107.6 (d, C-2),
116.4 (d, C-3), 119.6, 125.5, 125.8, 134.2 (4 d, C-6, C-7, C-8, C-9),
130.7 (s, C-5a), 136.0 (s, C-9b), 146.4 (s, C-1), 162.6 (s, C-5); the
signal for C-9a was not detected.
MS (EI, 80 eV, 50 °C): m/z (%) = 199 (80, [M+]), 183 (100, [M+ –
+
+
Me]), 130 (27, [C8H4NO2 ]), 102 (25), 76 (10, [C6H4 ]), 43 (14,
[CHNO+]), 28 (28, [CO+]).
IR (KBr): 3185–2950 (NH, =CH), 1725 (C=O), 1680 (C=C) cm–1.
UV (CH2Cl2): lmax (e) = 232 (17675), 257 (17358), 264 (17257),
298 (12257), 417 nm (2441).
HRMS (EI, 80 eV, 50 °C): m/z calcd for C12H9NO2 [M+]: 199.0633;
found: 199.0642.
Major Isomer
1H NMR (CDCl3, 500 MHz): d = 2.45 (s, 3 H, CH3), 3.81 (s, 3 H,
OCH3), 7.51–7.70 (m, 2 H, Ar), 7.88 (d, J = 7.3 Hz, 1 H, Ar), 8.61
(br s, 1 H, NH), 8.72 (d, J = 7.3 Hz, 1 H, Ar).
13C NMR (CDCl3, 125.7 MHz): d = 27.9 (q, C-3¢), 61.1 (q, OCH3),
123.6, 126.8, 131.0, 133.2 (4 d, C-4, C-5, C-6, C-7), 124.2 (s, C-3),
125.8 (s, C-1¢), 134.5, 137.7 (2 s, C-3a, C-7a), 169.9 (s, C-1), 196.9
(s, C-2¢).
1-(Benzyloxy)-5H-pyrrolo[2,1-a]isoindol-5-one (13b)
According to the general procedure, treatment of 11b (92 mg, 0.251
mmol) with AuCl3 (4 mg, 0.013 mmol) in CH2Cl2 (4 mL) yielded
27 mg (40%) of 13b as orange-yellow solid; mp 77–80 °C.
MS (EI, 80 eV, 70 °C): m/z (%) = 217 (100, [M+]), 202 (38, [M+ –
IR (KBr): 3110–3000 (=CH), 2930 (CH), 1725 (C=O), 1590 (C=C)
cm–1.
1H NMR (CDCl3, 500 MHz): d = 5.13 (s, 2 H, CH2Ph), 5.97 (d,
J = 3.4 Hz, 1 H, 2-H), 6.90 (d, J = 3.4 Hz, 1 H, 3-H), 7.06–7.11 (m,
1 H, Ar), 7.27–7.45 (m, 7 H, Ar, Ph), 7.59–7.63 (m, 1 H, Ar).
Me]), 187 (11, [M+ – 2 Me]), 174 (64, [M+ – CONH]), 160 (88), 132
+
(66), 103 (43), 76 (58, [C6H4 ]), 43 (49).
Anal. Calcd for C12H11NO3 (217.2): C, 66.35; H, 5.10; N, 6.45.
Found: C, 66.37; H, 5.02; N, 6.39.
13C NMR (CDCl3, 125.7 MHz): d = 73.2 (t, CH2Ph), 108.4 (d, C-2),
116.3 (d, C-3), 119.7, 125.6, 125.7, 127.4, 128.2, 128.6, 134.3 (7 d,
C-6, C-7, C-8, C-9, C6H5), 130.7 (s, C-5a), 135.9, 136.6 (2 s, C6H5,
C-9b), 145.0 (s, C-1), 162.7 (s, C-5); the signal for C-9a was not de-
tected.
Minor Isomer
1H NMR (CDCl3, 500 MHz): d = 2.42 (s, 3 H, CH3), 7.75, 7.88,
8.05, 8.15 (4 mc, each 1 H, Ar), 9.90 (s, 1 H, NH).
13C NMR (CDCl3, 125.7 MHz): d = 27.1 (q, C-3¢), 61.2 (q, OCH3),
124.1, 125.6, 131.0, 133.0 (4 d, Ar).
MS (EI, 80 eV, 70 °C): m/z (%) = 275 (50, [M+]), 184 (44, [M+ –
C7H7]), 132 (11), 130 (29, [C8H4NO+]), 102 (26, [C7H4N+]), 90
+
3-(1-Benzyloxy-2-oxopropylidene)-2,3-dihydro-1H-isoindol-1-
one (14b)
(100, [C7H7 ]).
HRMS (EI, 80 eV, 70 °C): m/z calcd for C17H11NO2 [M+]:
275.0946; found: 275.0952.
According to the general procedure, reaction of 7b (100 mg, 0.341
mmol) with 2 N H2SO4 (0.3 mL) in THF (4 mL) yielded after puri-
fication by column chromatography (CH2Cl2–MeOH, 98:2) 72 mg
(72%) of 14b as pale yellow solid, as a 88:12 mixture of diastere-
omers (determined by 1H NMR spectroscopy); melting range 175–
180 °C. The 13C NMR signals for the minor isomer are not given,
because they could not be assigned unambiguously.
1-(2-Trimethylsilyl)ethoxy-5H-pyrrolo[2,1-a]isoindol-5-one
(13c)
According to the general procedure, treatment of 11c (123 mg,
0.327 mmol) with AuCl3 (6 mg, 0.019 mmol) in CH2Cl2 (6 mL)
yielded 30 mg (32%) of 13c as orange-yellow oil which solidified
in the refrigerator.
IR (KBr): 3200 (CONH), 3100–2895 (CH), 1720 (C=O), 1680
(C=C) cm–1.
IR (film): 3110–2895 (CH), 1740 (C=O), 1620 (C=C) cm–1.
1H NMR (CDCl3, 500 MHz): d = 0.12 [s, 9 H, Si(CH3)3], 1.14 (t,
J = 8.0 Hz, 2 H, CH2TMS), 4.18 (t, J = 8.0 Hz, 2 H, OCH2), 5.84 (d,
J = 3.4 Hz, 1 H, 2-H), 6.91 (d, J = 3.4 Hz, 1 H, 3-H), 7.07 (mc, 1 H,
Ar), 7.14 (mc, 1 H, Ar), 7.61 (br d, J = 7.5 Hz, 1 H, Ar), 7.66 (d,
J = 7.5 Hz, 1 H, Ar).
Major Isomer
1H NMR (CDCl3, 500 MHz): d = 2.46 (s, 3 H, CH3), 4.88 (s, 2 H,
CH2Ph), 7.38–7.46 (m, 5 H, C6H5), 7.54–7.58 (m, 1 H, Ar), 7.61–
7.66 (m, 1 H, Ar), 7.81–7.84 (m, 2 H, NH, Ar), 8.65–8.69 (m, 1 H,
Ar).
13C NMR (CDCl3, 125.7 MHz): d = –1.2 [q, Si(CH3)3], 18.2 (t,
CH2TMS), 69.3 (t, CH2O), 108.3 (d, C-2), 116.5 (d, C-3), 119.7,
125.4, 125.7, 134.2 (4 d, C-6, C-7, C-8, C-9), 131.6 (s, C-5a), 135.5
(s, C-9b), 145.5 (s, C-1), 162.1 (s, C-5); the signal for C-9a was not
detected.
MS (EI, 80 eV, 40 °C): m/z (%) = 285 (5, [M+]), 257 (51, [M+ –
C2H4]), 242 (14, [M+ – C2H4 – Me]), 214 (13, [M+ – C2H4 – Me –
CO]), 130 (13), 102 (14), 73 (100, [TMS+]), 45 (12, [C2H5O+]).
13C NMR (CDCl3, 125.7 MHz): d = 28.8 (q, CH3), 76.0 (t, CH2Ph),
123.8, 128.4, 129.0, 129.1, 130.9, 130.9, 133.3 (7 d, Ar, C6H5),
127.8, 133.6, 134.4, 135.5, 136.3 (5 s, C-3a, C-7a, C-3, C-1¢, C6H5),
167.7 (s, C-1), 197.7 (s, C-2¢).
MS (EI): m/z (%) = 293 (3, [M+]), 265 (1, [M+ – CO]), 250 (1, [M+
– MeCO]), 221 (36, [M+ – C2H3O – CO]), 202 (14, [M+ – CH2Ph]),
+
173 (34, [M+ – C8H7O]), 160 (34), 102 (23), 91 (100, [C7H7 ]), 64
(12), 43 (33, [C2H3O+]).
HRMS (EI, 80 eV, 40 °C): m/z calcd for C16H19NO2Si [M+]:
HRMS (EI, 80 eV, 150 °C): m/z calcd for C18H15NO3 [M+]:
285.1185; found: 285.1174.
293.1051; found: 293.1058.
Acid-Induced Rearrangement of 7a–c; General Procedure
The allene adduct 7 (1 equiv) was dissolved in THF (7 mL/mmol)
and 2 N H2SO4 (0.36 mL/mmol) was added. The mixture was stirred
for 3 d at r.t. and diluted with H2O. The layers were separated and
Minor Isomer
1H NMR (CDCl3, 500 MHz): d = 2.38 (s, 3 H, CH3), 4.93 (s, 2 H,
CH2Ph), 7.48 (mc, 2 H, Ar), 7.88 (mc, 1 H, Ar), 8.00 (mc, 1 H, Ar),
9.96 (s, 1 H, NH).
Synthesis 2006, No. 8, 1351–1359 © Thieme Stuttgart · New York