The effect of substituents on the feasibility of azomethine - Azomethine isomerization: New synthetic opportunities for biomimetic transamination

Article abstract of DOI:10.1016/0040-4020(96)00920-9

The azomethine - azomethine isomerization of the Schiff bases derived from fluoroalkyl carbonyl compounds and arylmethylamines has been studied as a function of substitution on the amine site. The present study indicates that regardless of the nature of the substitution, the position of the isomerization equilibrium is overwhelmingly controlled by the electron-withdrawing effect of the perfluoroalkyl group, while the reaction rate strongly depends on both CH acidity and steric availability of the transferring proton. Specifically, we have found that the presence of electron-releasing substituent on the phenyl of the benzylamine site largely retards the isomerization of the corresponding imines. In contrary, azomethine-azomethine isomerizations of the imines derived from the benzylamines containing electron-withdrawing substituent on-the phenyl ring or picolylamines, possessing electron-deficient pyridine ring, occur with remarkably higher reaction rates as compared with the established isomerizations of N-benzylimines. In particular, the use of 4-picolylamine allows for truly biomimetic one-stage transamination of fluorocarbonyl compounds to afford the Schiff bases of the corresponding amines. The exciting synthetic aspects of this finding are demonstrated by the improved procedure for transamination of certain fluoroalkyl carbonyl compounds representing aldehydes, ketones, and β-keto carboxylic acids.