Enantiospecific synthesis of pyridinylmethyl pyrrolidinemethanols and catalytic asymmetric borane reduction of prochiral ketones

Abstract

Three chiral pyridinylmethyl pyrrolidinemethanol derivatives have been synthesized from N-alkylation of ( S)-α,α-diphenyl-2-pyrrolidinemethanol and N-carbonylation of l-proline methyl ester. The catalytic asymmetric borane reduction of prochiral ketones was examined in the presence of chiral oxazaborolidine catalysts prepared in situ from chiral pyridinylmethyl pyrrolidinemethanol derivatives. The corresponding chiral secondary alcohols were obtained with good to excellent enantiomeric excesses (up to 98% ee) using ( S)-2-(diphenylmethanol)-l-(2-pyridylmethyl)pyrrolidine 1 in THF at reflux and moderate to good enantiomeric excesses using C 2-symmetric compound 2 (up to 86% ee) in THF.