Synthesis of 5-(hydroxymethyl)pyrrolidin-2-ones by cyclization of amide dianions with epibromohydrin

Abstract

The reaction of amide and thioamide dianions with epibromohydrin resulted in regioselective formation of 5-(hydroxymethyl)pyrrolidin-2-ones (pyroglutaminols) and -thiones. The cyclization of the dianion of N-(2-tert-butylphenyl)acetamide with epibromohydrin afforded racemic axially chiral 1-(2-tert-butylphenyl)-5-(hydroxymethyl)pyrrolidin-2-one with high diastereoselectivity.