Enantioselective Nitrile Anion Cyclization to Substituted Pyrrolidines. A Highly Efficient Synthesis of (3 S, 4 R)-N-tert-Butyl-4-Arylpyrrolidine-3-Carboxylic Acid

…, R Cvetovich, J Amato, JC McWilliams…

Index: Chung, John Y. L.; Cvetovich, Raymond; Amato, Joseph; McWilliams, J. Christopher; Reamer, Robert; DiMichele, Lisa Journal of Organic Chemistry, 2005 , vol. 70, # 9 p. 3592 - 3601

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Citation Number: 38

Abstract

A practical asymmetric synthesis of N-tert-butyl disubstituted pyrrolidines via a nitrile anion cyclization strategy is described. The five-step chromatography-free synthesis of (3 S, 4 R)-1- tert-butyl-4-(2, 4-difluorophenyl) pyrrolidine-3-carboxylic acid (2) from 2-chloro-1-(2, 4- difluorophenyl)-ethanone achieved a 71% overall yield. The cyclization substrate was prepared via a catalytic CBS asymmetric reduction, t-butylamine displacement of the ...