σ N-C Bond Difunctionalization in Bridged Twisted Amides: Sew-and-Cut Activation Approach to Functionalized Isoquinolines

A rare example of highly selective sigma N-C bond difunctionalization in bridged twisted lactams through N-C cleavage has been achieved. In combination with the intramolecular Heck cyclization, this method affords a two-step bond reorganization event (sew-and-cut) to access functionalized isoquinoline ring systems directly with high atom economy. C-H bond functionalizations directed by a weakly coordinating bridged amide bond increase scaffold diversity. Preliminary mechanistic studies on the effect of amide distortion and the role of electrophile in-this unusual sigma N-C amide difunctionalization are described.