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.
Harunobu Mitsunuma (2026) studied this question.