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 of ketones, as ketone moieties are ubiquitously found in feedstock chemicals, synthetic building blocks and bioactive compounds. Specifically, we will: (i) expand the scope and utilities with activation of strained ketones for constructing complex ring systems, (ii) enable new and broadly applicable transformations with unstrained ketones in an atom-economical fashion, and (iii) explore a new activation mode that can shift the paradigm for ketone activation. The research proposed is expected to simplify synthesis through new strategic bond disconnections, allow for editing skeletons of complex molecules under redox-neutral conditions, and offer a byproduct-free approach to access organic building blocks.