Tunable regioselectivity for C–H alkynylation of weakly coordinating amides that tolerated strongly coordinating heterocycles

Abstract

A weakly coordinating amide-directed C–H alkynylation enables late-stage modification of complex drug and material analogues bearing multiple reactive C–H bonds. This approach achieves divergent regioselectivity in celecoxib and valdecoxib derivatives that contained strongly coordinating heterocycles, by exploiting complementary reactivity between amide substrates, metal catalysts, and haloalkyne coupling partners.