J. Christoffers et al.
FULL PAPER
bined organic layers were dried (MgSO4), filtered and the solvents
evaporated. The residue was submitted to column chromatography
(SiO2; toluene/EtOAc, 5:1) to yield pyrrole 9a (57 mg, 232 μmol,
24%) in a first fraction (Rf = 0.89) as a colorless solid (m.p.
137 °C). Secondly, spiropyrrolidone 7 (21 mg, 68 μmol, 7%, Rf =
0.44) was obtained, also as a colorless solid (m.p. 169 °C). Finally,
lactam 6a (88 mg, 0.27 mmol, 28%, Rf = 0.36) was obtained as a
yellow oil.
H), 7.16–7.23 (m, 2 H), 7.25–7.33 (m, 5 H), 7.35–7.45 (m, 1
H) ppm; minor conformer: δ = 1.31 (t, J = 7.1 Hz, 3 H), 2.99–3.05
(m, 1 H), 3.02 (s, 3 H), 3.45–3.58 (m, 2 H), 4.18–4.32 (m, 2 H),
5.59 (d, J = 7.4 Hz, 1 H), 7.07–7.13 (m, 1 H), 7.16–7.23 (m, 2
H), 7.25–7.33 (m, 5 H), 7.48–7.54 (m, 1 H) ppm. 13C{1H} NMR
(125 MHz, CDCl3); major isomer: δ = 13.22 (CH3), 32.29 (CH3),
35.53 (CH2), 41.16 (CH), 60.36 (CH2), 121.84 (CH), 125.07 (2 CH),
125.69 (CH), 126.78 (CH), 127.73 (2 CH), 127.76 (CH), 128.19
(CH), 128.28 (CH), 133.38 (C), 133.85 (C), 135.69 (C), 142.52 (C),
171.49 (C), 172.23 (C) ppm; minor conformer: δ = 13.25 (CH3),
32.73 (CH3), 33.57 (CH2), 45.05 (CH), 60.36 (CH2), 120.16 (CH),
124.86 (2 CH), 125.72 (CH), 126.24 (CH), 126.68 (CH), 127.73
(CH), 127.88 (2 CH), 128.99 (CH), 134.95 (C), 136.01 (C), 136.10
Methyl (Z)-2-Methyl-1-oxo-3-phenyl-1,2,5,6-tetrahydrobenzo[c]az-
ocine-5-carboxylate (6a): A double signal set (ratio 2:1) was observed
1
in the NMR spectra. H NMR (500 MHz, CDCl3); major isomer:
δ = 3.03 (s, 3 H), 3.05 (dd, J = 9.6, 15.7 Hz, 1 H), 3.61 (dd, J =
8.4, 15.7 Hz, 1 H), 3.77 (s, 3 H), 3.91 (dt, J = 9.5, 8.4 Hz, 1 H),
5.91 (d, J = 8.3 Hz, 1 H), 6.94–6.99 (m, 1 H), 7.12–7.18 (m, 2 H),
7.19–7.29 (m, 5 H), 7.34–7.39 (m, 1 H) ppm; minor isomer: δ =
2.99 (s, 3 H), 3.02–3.09 (m, 1 H), 3.46–3.54 (m, 2 H), 3.75 (s, 3 H),
5.63 (d, J = 7.4 Hz, 1 H), 7.06 (d, J = 7.4 Hz, 1 H), 7.19–7.29 (m,
5 H), 7.20–7.22 (m, 2 H), 7.46–7.50 (m, 1 H) ppm. 13C{1H} NMR
(125 MHz, CDCl3); major conformer: δ = 33.26 (CH3), 36.46
(CH2), 41.98 (CH), 52.40 (CH3), 122.60 (CH), 126.06 (2 CH),
126.68 (CH), 127.80 (CH), 128.68 (CH), 128.70 (2 CH), 129.16
(CH), 129.26 (CH), 134.26 (C), 134.77 (C), 136.63 (C), 143.62 (C),
172.41 (C), 173.66 (C) ppm; minor conformer: δ = 33.64 (CH3),
34.55 (CH2), 45.73 (CH), 52.48 (CH3), 120.90 (CH), 125.84 (2 CH),
126.71 (CH), 127.24 (CH), 127.64 (CH), 128.75 (CH), 128.88 (2
CH), 129.96 (CH), 135.80 (C), 136.98 (2 C), 144.83 (C), 171.25 (C),
(C), 143.72 (C), 170.33 (C), 170.73 (C) ppm. IR (ATR): ν = 3059
˜
(w), 2979 (m), 2934 (m), 1729 (s), 1687 (w), 1640 (vs), 1446 (m),
1369 (s), 1181 (s), 1027 (m), 862 (w), 768 (s), 746 (m), 697 (m),
637 (m) cm–1. HRMS (CI): calcd. for C21H22NO3 336.1600; found
336.1591 [M + H+].
Ethyl (Z)-2-Benzyl-1-oxo-3-phenyl-1,2,5,6-tetrahydrobenzo[c]-
azocine-5-carboxylate (6c): Benzylamine (864 mg, 8.06 mmol) and
oxo ester 5b (322 mg, 1.00 mmol) were converted according to the
procedure given for product 6b. Chromatography (SiO2; toluene/
EtOAc, 30:1; Rf = 0.23) gave the product 6c (98 mg, 87% purity
according to GLC, 0.21 mmol, 21%) as a yellow oil. A double sig-
nal set (ratio 9:1) was observed in the NMR spectra. 1H NMR
(500 MHz, CDCl3); major conformer: δ = 1.21 (t, J = 7.1 Hz, 3
H), 2.77–2.96 (m, 1 H), 3.13 (dd, J = 8.3, 16.6 Hz, 1 H), 3.42 (dd,
J = 8.3, 15.4 Hz, 1 H), 3.72 (d, J = 13.7 Hz, 1 H), 4.16 (q, J =
7.1 Hz, 2 H), 5.60 (d, J = 13.7 Hz, 1 H), 5.87 (d, J = 7.8 Hz, 1 H),
6.87–6.94 (m, 1 H), 7.06–7.31 (m, 12 H), 7.39–7.44 (m, 1 H) ppm;
minor conformer: δ = 3.70 (d, J = 14.1 Hz, 1 H), 5.53 (d, J =
14.1 Hz, 1 H), 5.65 (d, J = 7.6 Hz, 1 H) ppm; other signals were
172.22 (C) ppm. IR (ATR): ν = 3058 (w), 3023 (w), 2952 (m), 1733
˜
(s), 1686 (w), 1638 (vs), 1445 (m), 1370 (s), 1251 (m), 1198 (s), 1165
(s), 1105 (w), 1029 (w), 864 (w), 766 (s), 747 (vs), 697 (s), 636
(w) cm–1. HRMS (CI): calcd. for C20H20NO3 322.1443; found
322.1434 [M + H+].
5Ј-Hydroxy-1Ј-methyl-1,2Ј-dioxo-5Ј-phenylspiro[indane-2,3Ј-
pyrrolidine] (7): 1H NMR (500 MHz, CDCl3): δ = 2.48 (d, J =
14.0 Hz, 1 H), 2.67 (d, J = 14.0 Hz, 1 H), 2.67 (s, 3 H), 3.02 (d, J
= 17.1 Hz, 1 H), 3.87 (d, J = 17.1 Hz, 1 H), 5.72 (s, 1 H), 7.31–
7.37 (m, 1 H), 7.38–7.45 (m, 3 H), 7.51–7.56 (m, 3 H), 7.67 (dt, J
= 1.0, 7.7 Hz, 1 H), 7.79 (d, J = 7.7 Hz, 1 H) ppm. 13C{1H} NMR
(125 MHz, CDCl3): δ = 26.08 (CH3), 36.81 (CH2), 47.49 (CH2),
59.53 (C), 90.08 (C), 125.27 (CH), 126.19 (2 CH), 126.55 (CH),
128.10 (CH), 128.25 (CH), 128.63 (2 CH), 134.27 (C), 136.43 (CH),
hidden by the major isomer. IR (ATR): ν = 3062 (w), 3030 (w),
˜
2980 (m), 2933 (m), 1729 (vs), 1686 (s), 1642 (s), 1605 (w), 1494
(w), 1446 (m), 1390 (m), 1320 (m), 1287 (m), 1252 (m), 1182 (s),
1030 (m), 911 (m), 733 (vs), 699 (s), 635 (m) cm–1. MS (EI, 70 eV):
m/z (%) = 411 (1) [M+], 383 (6), 320 (25), 246 (35), 194 (10), 105
(9), 91 (100). HRMS (CI): calcd. for C27H26NO3 412.1913; found
412.1923 [M + H+].
Ethyl (Z)-2-(2-Ethoxyethyl)-1-oxo-3-phenyl-1,2,5,6-tetrahydro-
benzo[c]azocine-5-carboxylate (6d): EtOCH2CH2NH2 (357 mg,
4.00 mmol) and oxo ester 5b (161 mg, 500 μmol) were converted
according to the procedure given for product 6b. Chromatography
(SiO2; toluene/EtOAc, 5:1; Rf = 0.33) gave the product 6d (30 mg,
76 μmol, 15%) as a yellow oil. A double signal set (ratio 6:1) was
observed in the NMR spectra. 1H NMR (500 MHz, CDCl3); major
conformer: δ = 1.16 (t, J = 7.0 Hz, 3 H), 1.33 (t, J = 7.1 Hz, 3 H),
2.93 (ddd, J = 4.2, 6.0, 14.1 Hz, 1 H), 3.12 (dd, J = 7.4, 15.2 Hz,
1 H), 3.36–3.56 (m, 3 H), 3.62–3.67 (m, 2 H), 4.20 (dt, J = 9.0,
7.2 Hz, 1 H), 4.22–4.29 (m, 2 H), 4.50 (ddd, J = 4.3, 7.3, 14.1 Hz,
1 H), 6.00 (d, J = 7.0 Hz, 1 H), 6.98–7.03 (m, 1 H), 7.15–7.22 (m,
2 H), 7.25–7.29 (m, 5 H), 7.39–7.43 (m, 1 H) ppm; minor con-
former: δ = 1.12 (t, J = 7.0 Hz, 3 H), 5.71 (d, J = 8.3 Hz, 1 H) ppm;
other signals are hidden by the major isomer. 13C{1H} NMR
(125 MHz, CDCl3); major conformer: δ = 14.29 (CH3), 15.10
(CH3), 35.89 (CH2), 42.46 (CH), 44.65 (CH2), 61.23 (CH2), 66.16
(CH2), 67.40 (CH2), 124.96 (CH), 126.16 (2 CH), 126.76 (CH),
141.02 (C), 155.15 (C), 172.05 (C), 206.98 (C) ppm. IR (ATR): ν =
˜
3362 (m), 3071 (w), 2941 (w), 2914 (w), 1683 (vs), 1607 (w), 1420
(m), 1375 (m), 1330 (w), 1286 (m), 1221 (m), 1124 (w), 1071 (m),
1027 (w), 991 (m), 969 (m), 911 (m), 813 (w), 759 (s), 712 (s), 679
(m) cm–1. MS (ESI, positive mode): m/z (%) = 330 (100) [M + Na+],
290 (75) [M – H2O + H+]. HRMS (ESI, positive mode): calcd. for
C19H17NNaO3 330.1106; found 330.1114 [M + Na+].
Ethyl (Z)-2-Methyl-1-oxo-3-phenyl-1,2,5,6-tetrahydrobenzo[c]-
azocine-5-carboxylate (6b): A solution of MeNH2 (2 mol/L in THF,
1.0 mL, 2.0 mmol) was added to a suspension of oxo ester 5b
(322 mg, 1.00 mmol) in THF (1 mL) and the resulting mixture was
stirred for 16 h at 100 °C in a tightly closed reaction flask. After
cooling to ambient temperature, the mixture was diluted with water
(20 mL) and extracted with EtOAc (3ϫ20 mL). The combined or-
ganic layers were dried (MgSO4), filtered and the solvents evapo-
rated. The residue was purified by chromatography (SiO2; toluene/
EtOAc, 5:1; Rf = 0.29) to furnish the lactam 6b (135 mg, 127.58 (CH), 128.70 (CH), 128.72 (2 CH), 129.02 (CH), 129.42
0.38 mmol, 38%) as a yellow oil. A double signal set (ratio 2:1) was
(CH), 134.91 (C), 135.79 (C), 137.12 (C), 141.77 (C), 172.46 (C),
173.69 (C) ppm; signals of the minor isomer could not be assigned
observed in the NMR spectra. 1H NMR (500 MHz, CDCl3); major
isomer: δ = 1.33 (t, J = 7.1 Hz, 3 H), 3.05–3.11 (m, 1 H), 3.07 (s, with confidence. IR (ATR): ν = 3060 (w), 3025 (w), 2977 (m), 2931
˜
3 H), 3.64 (dd, J = 8.4, 15.7 Hz, 1 H), 3.84 (dt, J = 8.4, 9.4 Hz, 1 (m), 2867 (m), 1729 (s), 1641 (vs), 1446 (w), 1389 (m), 1181 (m),
H), 4.18–4.32 (m, 2 H), 5.88 (d, J = 8.2 Hz, 1 H), 6.97–7.03 (m, 1 1161 (m), 1113 (s), 1029 (m), 917 (w), 864 (w), 812 (w), 767 (s), 741
4236
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Eur. J. Org. Chem. 2011, 4231–4240