Catalytic formal [2+2+1] synthesis of pyrroles from alkynes and diazenes via Ti(II)/Ti(IV) redox catalysis

Abstract

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.