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

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.