A General Photocatalytic Platform for the Regioand Stereoselective β-Chloroacylation of Olefins using a Heteroleptic Copper(I) Complex

Atom Transfer Radical Addition (ATRA) of aroyl chlorides to access βchloroacyl derivatives via photoredox catalysis remains hamstrung by using precious iridium photocatalyst and activated alkenes as acceptors. This has prevented the implementation of a general catalytic strategy for the β-chloroacylation of alkenes. Here, we report a unified platform for the regioselective chlorocarbonylation of alkenes via visible-light-mediated ATRA of aroyl chlorides catalyzed by a heteroleptic Cu(I)-complex that enables rapid access to β-chloroketones. The catalytic process has extensive substrate scope, scalability, and functional group tolerance. The ATRA reaction was also performed with alkynes to facilitate the introduction of an unprecedented catalytic E-selective β-chlorovinyl ketone formation. The synthetic utility of the protocol has been corroborated through functionalization of complex substrates and post-modifications of the products. The real-time application of this method has further been demonstrated by the formal synthesis of pharmacologically relevant haloperidol, seratrodast, and the naturally occurring piperidine alkaloid (−)-sedamine. This study undergirds the exclusive role of a heteroleptic copper(I)-complex, which outperforms homoleptic copper(I)-complexes – well-known and efficient for many ATRA processes – owing to its longer excited-state lifetime and specialized ligand environment, enabling better stabilization and interaction with radical intermediates in its coordination sphere.