Iron‐Photocatalyzed C(sp ³ )–H Phosphonylation of Alkanes

ABSTRACT Alkyl phosphonate esters are valuable motifs that have broad synthetic utility and are commonly found in bioactive molecules. Therefore, many methods have been developed to enable efficient phosphonylations of organic molecules, typically involving the construction of C(sp 3 )–P bonds by substitutions of common functional groups with phosphorus(III) reagents. However, direct phosphonylations of unactivated C(sp 3 )–H bonds are rare and currently lack the substrate generality required for late‐stage introduction of phosphonate groups into complex molecules. Herein, we report a photoinduced C(sp 3 )–H phosphonylation of unactivated alkanes using a hydrogen atom transfer (HAT) strategy with an iron photocatalyst. Key to the success of the process was the development of a novel mandelonitrile‐derived phosphite radical trap, which is equipped with an oxidizing phenylacetonitrile radical leaving group that enables effective turnover of the photocatalyst. The method displays good functional group tolerance, high selectivity for phosphonylations of sterically unhindered C─H bonds, and was found to be applicable to regioselective late‐stage installation of phosphonate esters into complex molecules.