Production of Csp3-Csp3 Bonds through Palladium-Catalyzed Tsuji-Trost-Type Reactions of (Hetero)Benzylic Substrates

This review covers the formation of Csp(3)-Csp(3) bonds through Pd-catalyzed reactions of benzylic and heterobenzylic substrates bearing acetate, carbonate, phosphonate, or halide leaving groups, with malonate-type compounds, oxazoles, aldehydes, alpha,beta-unsaturated aldehydes, oxindoles, or azlactones. Some of these coupling reactions have been carried out efficiently under enantioselective conditions. In most cases the reaction involves nucleophilic addition to the eta(3)-benzylpalladium intermediate formed by elimination of the leaving group. Before the nucleophilic attack, however, this intermediate can equilibrate with another benzylpalladium complex, leading to the isomeric coupling product. Because the nucleophilic addition can lead to the dearomatization of the aryl unit, subsequent rearomatization can transform the Csp(3)-Csp(3) bond into a Csp(2)-Csp(3) bond. Intramolecular reactions between benzylic and nucleophilic units have been reported, as well as decarboxylative benzylations from substrates in which the leaving group contains a potential nucleophilic species.