6 - Nucleophilic Substitution Reactions on the Carboxyl Carbon (Except through Enolates)

Abstract

This chapter discusses the nucleophilic reactions on the carboxyl carbons present in carbonyl compounds and carboxyl compounds. The type of nucleophilic reaction that occurs depends exclusively on the nature of the substrate and hardly at all on the nucleophile. The typical reaction of carbonyl compounds with nucleophiles is the addition; the C=O bond disappears. Ketenes and other C=O-containing heterocumulenes also react with nucleophiles in addition reactions; the C=O double bond, however, is nonetheless retained. In contrast, C=O-containing carboxylic acid and carbonic acid derivatives react with nucleophiles in substitutionreactions. SN reactions convert carboxylic acid derivatives to other carboxylic acid derivatives, or convert carbonic acid derivatives to other carbonic acid derivatives, when a nucleophile containing a heteroatom attacks at the carboxyl carbon. When an organometallic compound is used as the nucleophile, SN reactions at the carboxyl carbon make it possible to synthesize aldehydes (from derivatives of formic acid), ketones, or—starting from carbonic acid derivatives— in some cases carboxylic acid derivatives. Similarly, when using a hydride transfer agent as the nucleophile, SN reactions at a carboxyl carbon allow the conversion of carboxylic acid derivatives into aldehydes. A key intermediate common to all of SN is the species in which the nucleophile is linked with the former carboxyl carbon for the first time. The tetrahedral intermediate is a high-energy intermediate. The larger the rate constant Kadd for the formation of the tetrahedral intermediate, the faster an acylating agent reacts with nucleophiles.