Isolation of methyl (RS)-1-tert-butoxycarbonyl-3-cyanomethyl-1,2-dihydro-2-oxo-5H-pyrrole-5-carboxylate, the key-intermediate in base-catalyzed formation of racemic products by 1,3-dipolar cycloadditions to methyl (S)-1-tert-butoxycarbonyl-3-[(E)-cyanomethylidene]-2-pyrrolidinone-5-carboxylate

✍ Scribed by Marko Škof; Samo Pirc; Simon Rečnik; Jurij Svete; Branko Stanovnik; Ljubo Golič; Lovro Selič

• Publisher: Journal of Heterocyclic Chemistry
• Year: 2002
• Tongue: English
• Weight: 81 KB
• Volume: 39
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570390516

✦ Synopsis

Abstract

Cycloadditions of various 1,3‐dipoles to methyl (S)‐1‐tert‐butoxycarbonyl‐3‐[(E)‐cyanomethylidene]‐2‐pyrrolidinone‐5‐carboxylate (9) were studied. Reactions of 9 with diazomethane (10) and 2,4,6‐trimethoxy‐benzonitrile oxide (11), carried out under neutral conditions, gave the corresponding optically active spiro compounds 16‐18 with low diastereoselectivity (20‐30% diastereomeric excess). On the other hand, reactions of 9 with nitrile oxide 11 and nitrile imines 14, 15, carried out in the presence of a base, afforded racemic pyrazolo and isoxazolo fused 2‐pyrrolidinones 21‐23 in 82‐86% diastereomeric excess. Optically active dipolarophile 9 was isomerized in the presence of basic alumina to give methyl (RS)‐1‐tert‐butoxy‐carbonyl‐3‐cyanomethyl‐1,2‐dihydro‐2‐oxo‐5__H__‐pyrrole‐5‐carboxylate (19). Treatment of the racemic dipolarophile 19 with dipoles 11 and 14, afforded fused 2‐pyrrolidinones 23 and 21. These observations support compound 19 as the key‐intermediate in the formation of racemic cycloadducts 21‐23.