Ni-Catalyzed Asymmetric Reductive Arylation of ⍺-Substituted Imides

An asymmetric Ni-catalyzed reductive cross-coupling of ⍺-substituted imides and (hetero)aryl halides has been developed to synthesize enantioenriched ⍺-aryl imides, a commonly found structural motif in bioactive molecules and proteolysis-targeting chimeras (PROTACs) designed for targeted protein degradation (TPD). Employing a two-strategy approach with judiciously designed functional group pairings of the electrophiles allows for the coupling of either electron-rich or electron-deficient aromatics and heteroaromatics in good yields and enantioselectivities.