Catalytic formal [2+2+1] synthesis of pyrroles from alkynes and diazenes via TiII/TiIV redox catalysis

Pyrroles are structurally important heterocycles. However, the synthesis of polysubstituted pyrroles is often challenging. Here, we report a multicomponent, Ti-catalysed formal [2+2+1] reaction of alkynes and diazenes for the oxidative synthesis of penta- and trisubstituted pyrroles: a nitrenoid analogue to classical Pauson–Khand-type syntheses of cyclopentenones. Given the scarcity of early transition-metal redox catalysis, preliminary mechanistic studies are presented. Initial stoichiometric and kinetic studies indicate that the mechanism of this reaction proceeds through a formally Ti II /Ti IV redox catalytic cycle, in which an azatitanacyclobutene intermediate, resulting from [2+2] alkyne + Ti imido coupling, undergoes a second alkyne insertion followed by reductive elimination to yield pyrrole and a Ti II species. The key component for catalytic turnover is the reoxidation of the Ti II species to a Ti IV imido via the disproportionation of an η 2 -diazene-Ti II complex. Pyrroles are a common substructure in pharmaceuticals, materials and natural products. Now a multicomponent, titanium-catalysed synthesis of polysubstituted pyrroles — a nitrenoid analogue of the Pauson–Khand reaction — is reported. Stoichiometric and kinetic studies suggest that the reaction proceeds through an unusual Ti II /Ti IV redox cycle.