Development of Catalyst Systems Enabling sp³ C-H Functionalization Reactions

The functionalization of the ubiquitous carbon-hydrogen (C-H) bonds in organic molecules via transition-metal catalysis represents an ideal molecular transformation for the efficient synthesis of pharmaceutical and agrochemical compounds, fulfilling the principles of both atom economy and step economy. However, sp³ C-H bonds in readily available hydrocarbon feedstocks are inert, and conventional single-catalyst activation strategies have fundamental limitations, including the need for high temperatures and the introduction of directing groups. To address these challenges, we developed a reaction design based on a synergistic catalyst system that integrates multiple catalysts with orthogonal functions, enabling a previously unprecedented and broadly applicable strategy for sp³ C-H bond functionalization via the catalytic generation of organometallic species. Specifically, a ternary catalyst system comprising a hydrogen atom transfer (HAT) catalyst that can promote C-H bond cleavage under mild conditions, a metal catalyst that enables diverse and stereoselective transformations, and a photoredox catalyst that mediates the electron-transfer process was established. This system enabled sp³ C-H bond functionalization under mild conditions with high functional-group compatibility. Through the identification of uniquely effective catalyst systems, this strategy enables novel catalytic nucleophilic addition reactions and acceptorless dehydrogenation directly from simple hydrocarbon substrates.