Anti-Markovnikov alkene hydroalkylation via iron photocatalysis

Abstract Hydroalkylation provides a direct approach to C( sp 3 )–C( sp 3 ) bond formation from abundant alkenes, yet general methods for linear-selective hydroalkylation remain limited, particularly for simple alkyl groups such as methyl and ethyl. Here we introduce traceless radical polarity reversal, in which a removable electron-withdrawing group promotes radical alkene addition and is subsequently deleted in situ under the reaction conditions. Using a visible-light-promoted iron-and-thiol dual-catalytic system, this strategy enables hydroalkylation reactions that were previously difficult to access, including hydromethylation, hydroethylation and hydrocyclobutylation, with high linear selectivity from simple malonic acids. The method also provides direct access to gem -monofluoroalkyl and gem -difluoroalkyl motifs from fluorinated malonic acids and enables efficient synthesis of bioactive targets, including a GPR119 agonist. Preliminary mechanistic studies support a dual-catalytic radical pathway involving visible-light-induced homolysis and hydrogen-atom transfer processes.