Hydroalkylation of Unactivated Alkenes with Amides via Photoredox Catalysis and Triple Hydrogen Atom Transfer

Abstract Radical‐mediated hydroalkylation of alkenes offers a more direct and atom‐economical route to α‐alkylated carbonyl compounds, enabling the construction of various drug scaffolds, natural products, and functional molecules. However, traditional protocols are generally restricted to active 1,3‐dicarbonyl compounds and often require oxidants, large excesses of substrates, and harsh reaction conditions. Herein, we present a photoinduced, general, and practical hydroalkylation of unactivated alkenes with amides. Both inter‐ and intramolecular hydroalkylation reactions are achieved under mild and metal‐free conditions. This method demonstrates excellent chemo‐, regio‐, and diastereoselectivity, along with broad substrate scope and excellent functional group tolerance. A range of short‐chain gaseous olefins, including ethylene, can also undergo the reaction successfully. Its versatility is further highlighted by diverse late‐stage modification and synthesis of structurally complex bioactive molecules. Mechanistic investigations reveal that the reaction proceeds via a triple hydrogen atom transfer (HAT) process involving both intra‐ and intermolecular steps. The success of this chemistry is attributed to the controlled generation of relatively weak electrophilic α‐carbonyl radicals and the strategic application of radical polarity‐match/mismatch effect to finely tune the reactivity between distinct radical species and unactivated alkenes or the HAT donor.