Modular Access to Medium-to-Large Sized Lactams through Alkyne-Bridging C–C Bond Activation of Unstrained Carbonyls

While the conversion of simple cyclic ketones to lactams via carbon-carbon (C-C) bond cleavage can be accomplished through classical Beckmann and Schmidt rearrangements, these methods suffer from inherent limitations. Beyond regioselectivity challenges, they permit the incorporation of only a single nitrogen atom into the parent carbocyclic framework. Herein, an efficient approach to access medium-to-large sized lactams was developed through an alkyne migratory insertion enabled C-C bond activation of unstrained ketones. Easily available <i>ortho</i>-alkynylaniline derivatives were incorporated regioselectively, leading to formation of a range of medium and large sized lactams in a modular manner. This methodology demonstrates exceptional substrate generality, good functional group tolerance, and direct applicability to biorelevant molecule modification with effective transfer of axial chirality.