This method achieves high enantioselectivity in chiral amine synthesis with Ni-catalysis, suggesting practical applications.
Chiral α-branched amines represent privileged structural motifs in pharmaceuticals, nature products, and chiral ligands. However, their enantioselective synthesis directly from readily available aryl/alkenyl halides remains challenges. Herein, we report a Ni-catalyzed asymmetric reductive coupling of diverse N-sulfonyl imines with aryl/alkenyl halides. Enabled by a modified chiral biimidazole ligand in conjunction with a cobalt phthalocyanine (CoPc) cocatalyst, this transformation achieves high enantioselectivity at remarkably mild conditions. Demonstrating exceptional generality (>85 substrates), the protocol enables the direct functionalization of complex drug-derived scaffolds (e.g., naproxen, ibuprofen, oxaprozin, gemfibrozil). The synthetic utility is further highlighted through late-stage functionalization and chemoselective derivatizations. DFT calculations support a mechanism involving Niᴵ-mediated oxidative cyclometallation, proceeding via a key aza-nickelacycle intermediate.
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Liu et al. (2025) studied this question.
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