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 ortho-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.