Synthetic studies for novel structure of α-nitrogenously functionalized α-fluorocarboxylic acids. Part 1. The first synthesis and reactions of N-protected α-fluoroglycines

Abstract

The first synthesis of the N-protected α-fluoro-α-amino acid esters 12, 13, 21 and 22, and the corresponding acids 16 and 24, is described. Reaction of ethyl and t-butyl bromofluoroacetates 4 and 9 with di-t-butyl and dibenzyl iminodicarboxylate potassium salts 10c and 20b gave the fluoroglycine derivatives 12, 13, 21 and 22, respectively. Hydrolysis of the ethyl ester 12 and the t-butyl ester 22 successfully afforded the key compounds N,N-di(t-butoxycarbonyl)-α-fluoroglycine 16 and N,N-di(benzyloxycarbonyl)-α-fluoroglycine 24. Conversion into the novel structure of α-fluoroglycine itself (1; R = H) by acidic N-deprotection of compound 16 or hydrogenative debenzylation of compound 24, however, failed to produce any decomposition products associated with dehydrofluorination.