Catalytic C−C Activation/Functionalization of Ketones and Amides

Abstract: We are engaged in the systematic efforts to exploit catalytic carbon–carbon (C−C) bond activation for developing new, general and synthetically useful methods. Our objective, in the proposed funding period, is to focus on C−C activation and functionalization of ketones and amides, as they are easily accessible and widely found in feedstock chemicals. Through harnessing the power of transition-metal catalysts, sometimes assisted by an organic activator, a suite of new, selective, and efficient methods involving C−C activation of ketones and amides will be developed. Specifically, we will: (i) explore new C−C activation modes that allow rapid access to complex sp3-rich ring systems, (ii) enable a novel and broadly applicable cross-coupling reaction via deacylation of unstrained ketones, and (iii) allow selective activation of α-C−C bonds of unstrained amides. The research proposed is expected to offer an atom-economical approach for preparing novel complex sp3-rich molecular scaffolds from readily available substrates, which should help to access greater chemical space beyond the “flatland”. It is also expected to simplify synthesis through new strategies for bond disconnections and to enable skeletal editing of complex molecules under redox-neutral conditions, capitalizing on C−C activation/functionalization of ketones and amides.