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]²⁵ _D = −35.8°C (C 1.5, CH₂Cl₂) diastereomer (92% d.e) as a major product.