Reductive Catalyst Regeneration Enables the General Cu-Catalyzed Atom Transfer Radical Addition with Primary Alkyl Halides

Abstract Primary alkyl halides are poor coupling partners in most atom transfer radical addition (ATRA) reactions due to their propensity to undergo off-cycle radical termination pathways, which lead to catalyst deactivation. Herein, we overcome this challenge in the Cu-catalyzed ATRA reaction though the addition of 1,1′-azobis(cyclohexanecarbonitrile), an in situ reducing agent. Under optimized conditions, the catalyst turnover is restored and challenging halides become competent coupling partners across a variety of substituted alkenes. This strategy enables the synthesis of a diverse array of biologically relevant synthetic intermediates, including α-haloboronic esters, sulfones, esters, amides, and arenes. The versatility and synthetic utility of these ATRA conditions are demonstrated in 48 examples and 13 subsequent functionalizations.