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(sp³)-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.