Rhodium-catalyzed oxidative cycloaddition of N-tert-butoxycarbonylhydrazones with alkynes for the synthesis of functionalized pyrroles via C(sp³)–H bond functionalization

Abstract

A rhodium(III)-catalyzed cycloaddition of N-tert-butoxycarbonylhydrazones with internal alkynes was developed. The reaction features a regioselective α-imino alkyl C(sp³)−H bond functionalization resulting in selective formation of highly functionalized NH-free pyrroles. Our studies showed that utilizing the N-tert-butoxycarbonyl (N-Boc) as the oxidizing directing group is critical for achieving the observed pyrrole formation versus the isoquinoline formation. To account for the pyrrole formation, we hypothesized that a prior tautomerization of the N-Boc-hydrazones to enamines should occur, followed by regioselective C(sp²)–H cleavage to form a putative five-membered rhodacycle. Subsequent coupling of the rhodacycle with the alkynes would afford the pyrrole products.