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Synlett 2007(8): 1259-1263  
DOI: 10.1055/s-2007-977461
LETTER
© Georg Thieme Verlag Stuttgart · New York

Novel Oxidation of Substituted Pyrrolidines by N-Bromosuccinimide - Rapid Synthesis of Pyrrolo[2,1-a]isoquinolines

Judit Tótha, Linda Váradia, András Dancsób, Gábor Blaskób, László Tőkea, Miklós Nyerges*a
a Organic Chemical Technology Research Group of the Hungarian Academy of Sciences, Budapest University of Technology and Economics, P.O.B. 91, 1521 Budapest, Hungary
b EGIS Pharmaceuticals Ltd., P.O.B. 100, 1475 Budapest, Hungary
Fax: +36(1)4633648; e-Mail: mnyerges@mail.bme.hu;
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Publication History

Received 11 January 2007
Publication Date:
08 May 2007 (online)

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Abstract

A new method for converting 1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolines into 5,6-dihydropyrrolo[2,1-a]isoquinolines using N-bromosuccinimide as an oxidant is presented.

Key words

azomethine ylides - cycloadditions - oxidation - pyrroles

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General procedure for the preparation of compounds 5a-l: The corresponding cycloadduct (4, 1.0 mmol) was dissolved in CHCl3 (10 mL) and NBS (0.17 g, 1.1 mmol) was added in one portion. The solution immediately turned yellow. After 30 min stirring H2O (10 mL) was added and the organic layer was washed with further portions of H2O (2 × 10 mL) and brine (10 mL), then dried (MgSO4) and evaporated in vacuo. The residue was triturated with cold EtOH and filtered to yield the title product as a yellow powder. All new compounds afforded correct elemental analyses and spectroscopic data.
Selected examples: Methyl 8,9-dimethoxy-1-nitro-2-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate (5a): IR (KBr): 2956, 2833, 1700, 1609, 1591, 1561, 1547, 1506, 1452, 1439, 1355, 1284, 1262, 1236, 1217, 1195, 1181, 1136, 1100, 1072, 1016 cm-1; 1H NMR (500 MHz, CDCl3): δ = 7.39 (m, 4 H, Ph-H and H-10), 7.29 (m, 2 H, Ph-H), 6.79 (s, 1 H, H-7), 4.58 (t, J = 6.7 Hz, 2 H, H-5), 3.94 (s, 3 H, OMe), 3.86 (s, 3 H, OMe), 3.53 (s, 3 H, OMe), 3.06 (t, J = 6.7 Hz, 2 H, H-6); 13C NMR (125 MHz, CDCl3): δ = 161.3 (q), 150.2 (q), 147.9 (q), 136.4 (q), 132.3 (q), 130.9 (q), 129.6 (q), 129.5 (2 × CH), 128.1 (q), 127.8 (CH), 127.6 (2 × CH), 117.2 (q), 114.7 (q), 110.5 (CH), 109.9 (CH), 56.5 (CH3), 56.0 (CH3), 51.4 (CH3), 43.0 (CH2), 28.8 (CH2).
Methyl 8,9-dimethoxy-2-(2-bromo-3,4,5-trimethoxy-phenyl)-1-nitro-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate (5e): IR (KBr): 2993, 2940, 2840, 1709, 1669, 1563, 1505, 1475, 1443, 1427, 1410, 1387, 1361, 1343, 1301, 1287, 1260, 1214, 1195, 1138, 1107, 1049, 1013 cm-1; 1H NMR (500 MHz, CDCl3): δ = 7.49 (s, 1 H, H-10), 6.79 (s, 1 H, H-7), 6.63 (s, 1 H, Ar2-6′H), 4.61 (m, 2 H, H-5), 3.96 (s, 3 H, OMe), 3.95 (s, 3 H, OMe), 3.93 (s, 3 H, OMe), 3.89 (s, 3 H, OMe), 3.83 (s, 3 H, OMe), 3.06 (m, 2 H, H-6); 13C NMR (125 MHz, CDCl3): δ = 160.9 (q), 152.2 (q), 150.7 (q), 150.4 (q), 147.7 (q), 142.5 (q), 131.6 (q), 131.5 (q), 129.7 (q), 128.0 (q), 127.4 (q), 118.6 (q), 117.1 (q), 111.0 (q), 110.5 (CH), 110.4 (CH), 109.8 (CH), 61.2 (CH3), 61.0 (CH3), 56.13 (CH3), 56.12 (CH3), 56.0 (CH3), 51.7 (CH3), 43.0 (CH2), 28.8 (CH2).
3-(4-Bromobenzoyl)-2-(2-chlorophenyl)-8,9-dimethoxy-1-nitro-5,6-dihydropyrrolo[2,1-a]isoquinoline (5k): IR (KBr): 3010, 2943, 1633, 1586, 1502, 1471, 1442, 1405, 1355, 1261, 1218, 1148, 1095, 1068, 1056, 1014 cm-1; 1H NMR (500 MHz, CDCl3): δ = 7.54 (s, 1 H, H-10), 7.41 (d, J = 8.4 Hz, 2 H, Ar3-2′ and 6′H), 7.25 (d, J = 8.4 Hz, 2 H, Ar3-3′ and 5′H), 7.19 (d, J = 7.9 Hz, 1 H, Ar2-6′H), 7.07 (t, J = 7.9 Hz, 1 H, Ar2-5′H), 6.97 (d, J = 7.9 Hz, 1 H, Ar2-3′H), 6.95 (d, J = 7.9 Hz, 1 H, Ar2-4′H), 6.81 (s, 1 H, H-7), 4.45 (m, 1 H, H-5), 4.34 (m, 1 H, H-5), 3.96 (s, 3 H, OMe), 3.90 (s, 3 H, OMe), 3.10 (m, 2 H, H-6); 13C NMR (125 MHz, CDCl3): δ = 186.6 (q), 150.6 (q), 147.8 (q), 136.7 (q), 134.3 (q), 133.1 (q), 132.3 (CH), 132.2 (q), 131.0 (q), 130.9 (2 × CH), 130.5 (2 × CH), 129.3 (CH), 129.1 (CH), 128.3 (q), 127.5 (q), 126.7 (q), 126.3 (CH), 125.3 (q), 117.0 (q), 110.6 (CH), 110.5 (CH), 56.2 (CH3), 56.0 (CH3), 43.3 (CH2), 29.0 (CH2).