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

Abstract

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 .