Tunable Regioselectivity for C-H Alkynylation of Weak Coordinating Amides that Tolerated Strongly Coordinating Heterocycles

Abstract

Herein, we report a weakly coordinating amide-directed regioselective C–H alkynylation, enabling late-stage, site-specific modification of intricate drug and material analogues containing multiple reactive C–H bonds. Notably, this approach achieves divergent regioselectivity in celecoxib and valdecoxib derivatives, tolerating strongly coordinating heterocycles by leveraging complementary reactivity patterns between amide substrates, metal catalysts, and haloalkyne coupling partners.