Alkylation of chiral 2-(aminomethyl)oxazolines

Abstract

Chiral 2-(aminomethyl)oxazolines 3 and 7, in which the heterocycle is derived from (R)-phenylglycinol, are synthesized and studied in alkylation reactions involving strong base and alkyl halides. The tertiary amine derivative 3 is alkylated efficiently at the α-carbon centre with no stereochemical induction, while the tertiary carbamate 7 is alkylated in moderate yield and reasonable diastereomeric excess. The stereochemical control observed in the latter case can be explained by the preferred formation of an E-enolate during the deprotonation step by prior complexation of the carbamate carbonyl group to the base.