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

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.