Expedient Preparation of All Isomers of 2-Aminocyclobutanecarboxylic Acid in Enantiomerically Pure Form

Abstract

A short, convenient, gram scale protocol has been established to allow facile access to all four stereoisomers of 2-aminocyclobutanecarboxylic acid, each in enantiomerically pure form (ee >99%). Starting from the readily available cis racemate, the procedure combines efficient alpha-phenylethylamine derivative resolution and controlled cis-to-trans epimerization procedures, and proceeds with invariably high yields.