S. Comesse et al.
FULL PAPER
5.42 (d, J = 15.7 Hz,1 H), 5.72 (d, J = 15.4 Hz, 1 H), 7.00 (d, J = (75 MHz, CDCl3) (mixture of both diastereoisomers): δ = 40.5 (C),
7.8 Hz, 1 H), 7.25 (dd, J = 10.2, 5.1 Hz, 3 H), 7.38–7.67 (m, 9 H) 40.7 (C), 43.1 (CH2), 43.2 (CH2), 45.0 (CH2), 45.1 (CH2), 48.3 (C),
ppm. 13C NMR (75 MHz, CDCl3): δ = 14.1 (CH3), 40.4 (CH2), 49.3 (C), 65.5 (C), 65.5 (C),108.0 (CH), 108.5 (CH), 120.9 (CH),
40.7 (CH2), 44.2 (CH2), 49.7 (C), 62.2 (CH2), 66.3 (CH), 109.6 122.3 (CH), 122.6 (CH), 124.1 (CH), 126.1–128.2 (unresolved),
(CH), 122.0 (CH), 123.6 (CH), 126.6 (CH), 127.2 (3 CH), 127.9 132.0 (C), 132.4 (CH), 136.6 (CH), 133.8 (C), 134.0 (C), 134.4 (C),
(CH), 128.1 (CH), 129.0 (2 CH), 129.3 (CH), 133.0 (C), 135.2 (C), 134.5 (C), 135.0 (C), 140.5 (C), 140.9 (C), 171.3 (C), 171.6 (C),
132.1 (CH), 137.4 (C), 141.5 (C), 168.0 (C), 172.2 (C), 174.5 (C) 172.8 (C), 176.0 (C), 192.7 (C), 193.7 (C) ppm.
ppm.
1,1Ј-Dibenzyl-2Ј-phenyl-1,2-dihydrospiro[indole-3,3Ј-pyrrolidine]-
2,5Ј-dione (11k): Purified by chromatography (AcOEt/cyclohexane,
1:4). Yield: 70%, dr = 75:25. The major diastereoisomer was iso-
Ethyl 1-Benzyl-5-chloro-2,5Ј-dioxo-1Ј-(thiophen-2-ylmethyl)-1,2-di-
hydrospiro[indole-3,3Ј-pyrrolidine]-2Ј-carboxylate (11h): Purified by
chromatography (AcOEt/cyclohexane, 1:4) as a white solid. M.p.
113–116 °C. Yield: 49%, dr = 90:10. The major diastereoisomer
could be obtained in pure form (triturating with ether and fil-
tration). 1H NMR (300 MHz, CDCl3): δ = 1.15 (t, J = 7.1 Hz, 3
H), 2.46 (d, J = 16.6 Hz, 1 H), 3.19 (d, J = 16.6 Hz, 1 H), 3.97 (s,
1 H), 4.03–4.14 (m, 1 H), 4.11 (d, J = 15.4 Hz, 1 H), 4.18–4.28 (m,
1 H), 4.59 (d, J = 15.7 Hz, 1 H), 5.03 (d, J = 15.7 Hz, 1 H), 5.35
(d, J = 15.4 Hz, 1 H), 6.52 (d, J = 8.4 Hz, 1 H), 6.87–6.95 (m, 3
H), 7.05 (d, J = 8.3 Hz, 1 H), 7.15–7.28 (m, 6 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 14.2 (CH3), 40.4 (CH2), 40.5 (CH2), 44.3
(CH2), 49.8 (C), 62.3 (CH2), 66.0 (CH), 110.6 (CH), 122.7 (C),
126.8 (CH), 127.2 (2 CH), 127.3 (CH), 128.1 (CH), 128.3 (CH),
129.1 (2 CH), 129.2 (CH), 134.4 (C), 134.8 (C), 137.2 (C), 140.0
(C), 167.7 (C), 171.7 (C), 174.0 (C) ppm.
lated as a white solid. M.p. 223–226 °C. IR (neat): ν = 1714, 1612,
˜
1522, 1480 cm–1. 1H NMR (300 MHz, CDCl3): δ = 2.74 (d, J =
16.7 Hz, 1 H), 3.02 (d, J = 16.7 Hz, 1 H), 3.72 (d, J = 14.7 Hz, 1
H), 4.57 (d, J = 15.7 Hz, 1 H), 4.72 (s, 1 H), 4.89 (d, J = 15.7 Hz,
1 H), 5.25 (d, J = 14.7 Hz, 1 H), 6.42 (d, J = 7.6 Hz, 1 H), 6.65–6.79
(m, 4 H), 6.89–7.19 (m, 14 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 40.5 (CH2), 43.88 (CH2), 45.4 (CH2), 53.1 (C), 68.4 (CH), 109.1
(CH), 122.3 (CH), 124.8 (CH), 127.2 (2 CH), 127.7 (CH), 127.8
(CH), 128.0 (CH), 128.4 (2 CH), 128.7–128.8 (9 CH and 2 C), 134.0
(C), 135.4 (C), 142.3 (C), 173.6 (C), 177.5 (C) ppm. HRMS: calcd.
for C31H26N2O2 [M + H+] 459.1994; found 459.1999.
1,1Ј-Dibenzyl-5-chloro-2Ј-phenyl-1,2-dihydrospiro[indole-3,3Ј-pyr-
rolidine]-2,5Ј-dione (11l): Purified by chromatography (AcOEt/cy-
clohexane, 1:4). Yield: 61%, dr = 75:25. The major diastereoisomer
was isolated as a white solid. M.p. 188–191 °C. IR (neat): ν = 1714,
˜
Ethyl 1,1Ј-Dibenzyl-2,5Ј-dioxo-1,2-dihydrospiro[indole-3,3Ј-pyrrol-
idine]-2Ј-carbonitrile (11i): Purified by chromatography (AcOEt/cy-
clohexane, 1:4). Yield: 50%, dr = 90:10. The major diastereoisomer
1612, 1485 cm–1. 1H NMR (300 MHz, CDCl3): δ = 2.80 (d, J =
16.6 Hz, 1 H), 3.08 (d, J = 16.6 Hz, 1 H), 3.80 (d, J = 14.7 Hz, 1
H), 4.65 (d, J = 15.7 Hz, 1 H), 4.77 (s, 1 H), 4.94 (d, J = 15.7 Hz,
1 H), 5.35 (d, J = 14.7 Hz, 1 H), 6.40 (d, J = 8.3 Hz, 1 H), 6.66 (d,
J = 2.1 Hz, 1 H), 6.86 (d, J = 6.6 Hz, 1 H), 6.97 (dd, J = 8.4,
2.1 Hz, 1 H), 7.00–7.07 (m, 2 H), 7.17–7.34 (m, 11 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 40.5 (CH2), 44.2 (CH2), 45.6 (CH2),
53.4 (C), 68.2 (CH), 110.2 (CH), 125.4 (CH), 127.3 (2 CH), 128.0
(3 CH), 128.8 (2 CH), 128.9 (2 CH), 128.9 (4 CH and 1 C), 129.0
(2 CH), 129.1 (CH), 130.4 (C), 133.8 (C), 135.1 (C), 135.4 (C),
140.9 (C), 173.3 (C), 177.2 (C) ppm. C31H25ClN2O2 (493.00): calcd.
C 75.52, H 5.11, N 5.68; found C 75.26, H 5.27, N 5.89. The minor
diastereoisomer was isolated as a white solid. M.p. 183–187 °C. 1H
NMR (300 MHz, CDCl3): δ = 2.69 (d, J = 17.0 Hz, 1 H), 3.09 (d,
J = 17.0 Hz, 1 H), 3.63 (d, J = 14.4 Hz, 1 H), 4.14 (d, J = 15.7 Hz,
1 H), 4.48 (s, 1 H), 4.89 (d, J = 15.7 Hz, 1 H), 5.26 (d, J = 14.4 Hz,
1 H), 6.54 (d, J = 5.7 Hz, 1 H), 6.51–6.55 (m, 2 H), 6.98–7.33 (m,
15 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 40.4 (CH2), 43.9
(CH2), 45.2 (CH2), 52.7 (C), 69.9 (CH), 110.3 (CH), 122.9 (CH),
126.9 (2 CH), 127.7 (CH), 128.2 (2 CH), 128.4 (C), 128.8 (6 CH),
128.9 (7 CH), 129.2 (CH), 132.8 (C), 133.3 (C), 134.8 (C), 135.5
(C),141.1 (C), 172.5 (C), 175.2 (C) ppm.
was isolated as a white solid. M.p. 113–116 °C. IR (neat): ν = 2400,
˜
1719, 1615 cm–1. 1H NMR (300 MHz, CDCl3): δ = 2.66 (d, J =
16.9 Hz, 1 H), 2.92 (d, J = 16.9 Hz, 1 H), 4.00 (d, J = 14.9 Hz, 1
H), 4.42 (s, 1 H), 4.74 (d, J = 15.8 Hz, 1 H), 4.80 (d, J = 15.8 Hz,
1 H), 5.26 (d, J = 15.9 Hz, 1 H), 6.68 (d, J = 7.8 Hz, 1 H), 7.02 (t,
J = 7.6 Hz, 1 H), 7.07–7.28 (m, 11 H), 7.31 (d, J = 7.5 Hz, 1 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 40.1 (CH2), 44.4 (CH2),
46.0 (CH2), 49.1 (C), 55.3 (CH), 110.2 (CH), 113.8 (C), 124.0 (CH),
124.0 (CH), 127.2 (2 CH), 127.7 (C), 128.1 (CH), 128.7 (CH), 128.8
(2 CH), 129.1 (2 CH), 129.3 (2 CH), 130.4 (CH), 133.9 (C), 134.8
(C), 142.4 (C), 170.8 (C), 175.1 (C) ppm. C26H21N3O2 (407.47):
calcd. C 76.64, H 5.19, N 10.31; found C 76.66, H 5.23, N 10.29.
The minor diastereoisomer was isolated as a white solid. M.p. 176–
1
179 °C. H NMR (300 MHz, CDCl3): δ = 2.64 (d, J = 17.1 Hz, 1
H), 3.15 (d, J = 17.1 Hz, 1 H), 4.02 (d, J = 14.8 Hz, 2 H), 4.19 (s,
1 H), 4.75 (d, J = 15.5 Hz, 1 H), 4.98 (d, J = 15.5 Hz, 1 H), 5.31
(d, J = 14.8 Hz, 1 H), 6.69 (d, J = 7.9 Hz, 1 H), 6.82–6.99 (m, 2
H), 7.04–7.41 (m, 11 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
40.1 (CH2), 44.5 (CH2), 45.9 (CH2), 48.7 (C), 55.4 (CH), 110.2
(CH), 113.5 (C), 122.2 (CH), 123.7 (CH), 127.7 (2 CH), 128.2
(CH), 128.8 (CH), 129.0 (2 CH), 129.1 (2 CH), 129.4 (2 CH), 130.2
(CH), 134.2 (C), 135.0 (C), 142.3 (C), 170.8 (C), 173.9 (C) ppm.
General Procedure for the Synthesis of Carboxylic Acid Derivatives
14: A mixture of tricyclic spirooxindole 11a–d (1.0 mmol) and
LiOH (6.0 mmol) in THF/H2O (5:1, 12 mL) was stirred at room
temperature for 3 d. THF was removed in vacuo, and the aqueous
phase was washed with EtOAc (2 ϫ 2 mL) and acidified to pH =
1. After extraction with EtOAc (3 ϫ 5 mL), the organic layers were
combined, dried with MgSO4 and the solvents evaporated. The
acid derivatives 14 were directly used in the next step without fur-
ther purification.
2Ј-Benzoyl-1,1Ј-dibenzyl-1,2-dihydrospiro[indole-3,3Ј-pyrrolidine]-
2,5Ј-dione (11j): Purified by chromatography (AcOEt/cyclohexane,
1:4) as a colorless oil. Yield: 48%, dr = 55:45. IR (neat): ν = 1704,
˜
1614, 1525, 1488 cm–1. 1H NMR (300 MHz, CDCl3) (mixture of
both diastereoisomers): δ = 2.50 (d, J = 16.5 Hz, 0.55 H), 2.65 (d,
J = 16.8 Hz, 0.45 H), 3.11 (d, J = 16.8 Hz, 0.45 H), 3.23 (d, J =
16.5 Hz, 0.55 H), 3.27 (d, J = 14.5 Hz, 0.55 H), 3.87 (s, 1 H), 4.11
(d, J = 14.6 Hz, 0.55 H), 4.23 (d, J = 15.4 Hz, 0.45 H), 4.25 (d, J
1,1Ј-Dibenzyl-2,5Ј-dioxo-1,2-dihydrospiro[indole-3,3Ј-pyrrolidine]-2Ј-
= 15.6 Hz, 0.45 H), 4.41 (s, 0.45 H), 4.42 (s, 0.55 H), 4.62 (d, J = carboxylic Acid (14a): This product was isolated as a white solid.
15.6 Hz, 0.45 H), 4.64 (d, J = 15.4 Hz, 0.55 H), 4.78 (s, 0.55 H), M.p. 112–117 °C. Yield: 84%, dr = 85:15. 1H NMR (300 MHz,
5.22 (s, 0.45 H), 5.32 (d, J = 14.5 Hz, 0.45 H), 5.42 (d, J = 14.6 Hz,
0.45 H), 6.28 (d, J = 7.6 Hz, 0.45 H), 6.61 (d, J = 7.6 Hz, 0.55 H),
6.67 (d, J = 6.8 Hz, 1 H), 6.75–6.49 (m, 15 H) ppm. 13C NMR
CDCl3): δ = 2.47 (d, J = 16.8 Hz, 1 H), 3.19 (d, J = 16.8 Hz, 1 H),
3.84 (d, J = 14.6 Hz, 1 H), 3.97 (s, 1 H), 4.59 (d, J = 15.6 Hz, 1
H), 4.95 (d, J = 15.6 Hz, 1 H), 5.25 (d, J = 14.5 Hz, 1 H), 6.60 (d,
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Eur. J. Org. Chem. 2011, 5303–5310