Convenient methods for the synthesis of chiral 2-phenylpyrrolidines

Abstract

Chiral N-α-methylbenzyl-2-phenylpyrrolidine has been prepared by the reaction of 1-phenyl-1,4-dibromobutane with S—(−)—α- methylbenzylamine. It has been also prepared by the condensation of methyl β-benzoylpropionate with S-(−)-α-methyl benzylamine followed by reduction using NaBH4/I2 and dil. HCl treatment. The diastereomers have been readily separated by chromatography on silica gel column. The lactam obtained by the condensation of S-valinol with β-benzoylpropionic acid on reduction using NaBH4/I2 in THF at -78°C for 6h and then rt for 6h gives (−)-N- [2-(1-hydroxy- 2(R)-isopropylethyl]- 5(S)-phenyl- 2-pyrrolidine, [α]D25 = −35.8°C (C 1.5, CH2C12) diastereomer (92% d.e) as a major product. © 1995, Taylor & Francis Group, LLC. All rights reserved.