NEIGHBORING GROUP PARTICIPATION BY CARBONYL GROUPS IN ESTER HYDROLYSIS

This chapter reviews the energetics of neighboring group participation and discusses the role of entropy; potential energy and the strain factors are evaluated. Likely factors of importance in enzymic catalysis are proximity, orientation, and steric strain. Intra-molecular catalysis has been conclusively demonstrated in a diverse range of esters undergoing alkaline hydrolysis and having suitably orientated acyl groups. This gives rise to significantly favorable pathways, involving neighboring group participation by either the monoanion of the hydrate of the acyl carbonyl group, the usual mode or the carbanion derived from a keto group having α-hydrogens. These pathways can be demonstrated in a number of different ways. For carbonyl group participation, the rate-determining step can be either the formation of the monoanion of the hydrate or the intra-molecular nucleophilic attack. This appears to depend on the system under study: the particular neighboring group, leaving group, and template involved. For systems involving formyl group participation, the hydration process has been sometimes considered to be the rate-determining step, while for those involving benzoyl group participation, the rate-determining step often appears to be the intra-molecular process. © 1993, Academic Press Limited.