Enantioselective Functionalization of Light Alkanes and C(sp 3 )–H Bonds via Photoinduced Palladium Catalysis

The direct and selective functionalization of abundant light alkanes (C1–C4) is a long-standing challenge in chemical synthesis, and methods to achieve this goal in an enantioselective fashion have remained an unsolved problem due to the high inertness of alkane C–H bonds. Here, we report a photoinduced, palladium-catalyzed, three-component reaction that allows the first enantioselective dialkylation of 1,3-dienes using light alkanes and other unactivated C(sp 3 )–H feedstocks. The strategy relies on a photogenerated aryl radical to initiate a hydrogen atom transfer (HAT) cascade, activating even the strongest C–H bonds in methane under mild conditions. This versatile methodology provides access to a diverse array of valuable chiral products in high yields and with excellent diastereo- and enantioselectivities. The protocol exhibits a broad scope, encompassing gaseous alkanes, cyclic hydrocarbons, ethers, and carbonyl compounds. Continuous-flow compatibility addresses practical challenges of handling gaseous substrates. Experimental and computational studies confirm that an excited-state palladium-mediated radical pathway is key for achieving stereocontrol and enabling the conversion of the simplest hydrocarbon feedstocks into enantiomerically enriched molecules.