Asymmetric Synthesis of 2,3-Methanohomoserine: A General Approach to Chiral 2-Substituted Cyclopropane Amino Acids

Article abstract of DOI:10.1021/jo00296a046

Double deprotonation-alkylation of the chiral aminonitrile synthon (R)-N-(cyanomethyl)-4-phenyloxazolidine (1) with LDA-HMPA and either epibromohydrin or glycidyl triflate gave in good yield the 2-(hydroxymethyl)cyclopropyl derivative in which two of the four possible diastereoisomeric forms predominated.A combination of simple chemical transformations of the cyclopropane C-1 substituents and chromatographic separation furnished two optically pure 2,3-methanohomoserines, functionalized as the methyl ester 11a and the γ-lactone 10b, respectively.These compounds can be converted into the free amino acids upon treatment with aqueous base and are proposed as useful intermediates in the asymmetric synthesis of other cyclopropane amino acids through subsequent manipulation of the 2-hydroxymethyl substituent.