From Esters to Benzodiazepines: A Two-Step Nickel-Iridium Catalytic Pathway via Amide Intermediates.

Herein, we report a NiCl2·DPEPhos catalyzed chemoselective activation of the C(acyl)-O bond in functionalized esters toward the synthesis of amino-hydroxy-amides using ambident amino alcohols. [IrCp*Cl2]2 catalyzed intramolecular cyclization of amino-hydroxy-amides via borrowing hydrogenation, afforded therapeutically beneficial 1,4-benzodiazepin-5-ones. A plausible mechanism for both steps has been elucidated. The 1,4-benzodiazepin-5-one frameworks were structurally diversified through postsynthetic modification. This protocol enables access to natural products such as Circumdatin F and Circumdatin H, further underscoring its potential.