Photocatalytic anti-Markovnikov hydro- and haloazidation of alkenes

Abstract Hydroazidation of alkenes provides a direct entry to alkyl azides, which are prevalent structural motifs in medicine development and chemical biology probes. While direct access to anti-Markovnikov hydroazidation products has seen recent progress, these protocols are restricted to highly oxidative hypervalent iodine reagents or superstoichiometric metal salts under photochemical conditions with moderate olefin generality. Thus, the development of a mild, catalytic, redox-neutral hydroazidation with high anti-Markovnikov regioselectivity compatible with diverse classes of alkene remains challenging. Here we report a photocatalytic anti-Markovnikov hydroazidation of alkenes enabled by cooperative ligand-to-metal charge transfer (LMCT) and hydrogen atom transfer (HAT). Critical to this protocol is the use of ligand to achieve efficient visible-light induced homolysis of iron azide species and the cooperation with thiol catalysts to promote this redox-neutral process and address previous challenging substrates. Additionally, the photocatalytic system enables a regioselective haloazidation via a tandem LMCT/ halogen atom transfer (XAT) process with judicious choice of halogenating reagents. Preliminary mechanistic studies support a radical nature of this cooperative system and suggest it to be a powerful manifold in olefin hydro- and di-functionalization.