THE EFFECT OF SUBSTITUENTS ON THE FEASIBILITY OF AZOMETHINE-AZOMETHINE ISOMERIZATION - NEW SYNTHETIC OPPORTUNITIES FOR BIOMIMETIC TRANSAMINATION

The azomethine-azomethine isomerization of the Schiff bases derived fr om fluoroalkyl carbonyl compounds and arylmethylamines has been studie d as a function of substitution on the amine site. The present study i ndicates that regardless of the nature of the substitution, the positi on of the isomerization equilibrium is overwhelmingly controlled by th e electron-withdrawing effect of the perfluoroalkyl group, while the r eaction rate strongly depends on both CH acidity and steric availabili ty of the transferring proton. Specifically, we have found that the pr esence of electron-releasing substituent on the phenyl of the benzylam ine site largely retards the isomerization of the corresponding imines . In contrary, azomethine-azomethine isomerizations of the imines deri ved from the benzylamines containing electron-withdrawing substituent on the phenyl ring or picolylamines, possessing electron-deficient pyr idine ring, occur with remarkably higher reaction rates as compared wi th the established isomerizations of N-benzylimines. In particular, th e use of 4-picolylamine allows for truly biomimetic one-stage transami nation of fluorocarbonyl compounds to afford the Schiff bases of the c orresponding amines. The exciting synthetic aspects of this finding ar e demonstrated by the improved procedure for transamination of certain fluoroalkyl carbonyl compounds representing aldehydes, ketones, and b eta-keto carboxylic acids. Copyright (C) 1996 Elsevier Science Ltd