Rapid formation of Csp3-Csp3 bonds through copper-catalyzed decarboxylative Csp3-H functionalization

Transition-metal-catalyzed decarboxylative and C -H functionalization strategy for the construction of Csp(2)-Csp(2), Csp(2)-Csp, and Csp(2)-Csp(3) bonds has been extensively studied. However, research surveys of this synthetic strategy for the Csp(3)-Csp(3) bond forming reactions are surprisingly scarce. Herein, we present an efficient approach for the rapid formation of Csp(3) -Csp(3) bond through copper-catalyzed decarboxylative Csp(3)-H functionalization. The present method should provide a useful access to C-3-substituted indole scaffolds with possible biological activities. Mechanistic experiments and DFT calculations supported a dual-Cu(II)-catalytic cycle involving rate-determining decarboxylation in an outer-sphere radical pathway and spin-crossover-promoted C -C bond formation. This strategy offers a promising synthesis method for the construction of Csp(3 )-Csp(3) bond in the field of synthetic and pharmaceutical chemistry and extends the number of still limited copper-catalyzed decarboxylative Csp(3) -Csp(3) bond forming reaction. (C) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

Transition-metal-catalyzed decarboxylative and C-H functionalization strategies have been extensively studied for the construction of Csp(2)-Csp(2), Csp(2)-Csp(3), and Csp(2)-Csp(3) bonds. However, research on the synthesis of Csp(3)-Csp(3) bonds using this strategy is surprisingly scarce. In this study, an efficient approach for the rapid formation of Csp(3)-Csp(3) bonds through copper-catalyzed decarboxylative Csp(3)-H functionalization is presented. This method offers a promising synthesis method for Csp(3)-Csp(3) bond construction in the field of synthetic and pharmaceutical chemistry.