Metal-Catalyzed Ionic Decarboxylative Cross-Coupling Reactions of C(sp3) Acids: Reaction Development, Mechanisms, and Application

The direct transition-metal-catalyzed conversion of carboxylic acid groups into other C–C or C–X bonds provides a complementary bond disconnection to traditional cross-coupling manifolds. Decarboxylative coupling strategies can be divided into two mechanistic frameworks: decarboxylative homolysis processes that generate radicals and decarboxylative heterolysis processes that generate carbanions. The challenge of both inducing decarboxylation with unmodified substrates and enabling efficient interception by a suitable transition-metal complex has made achieving general approaches to catalytic cross-couplings of carboxylic acids elusive. Thus, more wasteful indirect strategies involving preactivation of the acid unit are more common. This Perspective article highlights recent work in the area of metal-catalyzed ionic decarboxylative cross-coupling reactions of unmodified C(sp3) carboxylic acids. In these processes, the carboxylic acid unit serves as a surrogate for nucleophiles normally generated by deprotonation or by the use of organometallic reagents. In many cases, this approach can allow for alkylation reactions under less-basic conditions, improving functional group compatibility, ease of access to starting materials, and inhibit undesirable overfunctionalization of products. Commentary on reaction development, mechanism, and application is provided along with comparisons to related transformations.