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

Differences between the elimination of early and late transition metals: DFT mechanistic insights into the titanium-catalyzed synthesis of pyrroles from alkynes and diazenes

“…Tonks et al explored the disproportionation mechanism and proposed two possible mechanisms. 4 In agreement with their proposal, our energetic results rule out the mechanism occurring via passing a Ti II complex formed by dissociating azobenzene from IM5 (Fig. S4†).…”

“…, hexamethylbenzene) could be obtained. 4 Our predicted mechanism is able to explain this experimental observation. Referring to Fig.…”

“…This somewhat high barrier explains why these reactions needed to be performed at elevated temperatures (110.0 °C, eqn (1)). 4 Briefly, our computed energetics demonstrates the feasibility of the catalytic cycle proposed by Tonks et al 4 Furthermore, we gained an insight into the mechanism for the C–N bond formation stage.…”

“…3 Nevertheless, Odom et al 1 a prospected that “ this relative lack of diversity is largely due to the need for further development rather than an inherent lack of utility ”. Indeed, Tonks et al 4 recently accomplished pyrrole synthesis from alkynes and diazenes ( e.g. , eqn (1)), catalyzed by a titanium imido complex 1cat .…”

Redox non-innocence permits catalytic nitrene carbonylation by (dadi)TiNAd (Ad = adamantyl)

“…41 While the former is unlikely to involve formal RNI, the capability of Cp to covalently distribute charge is remarkable; 42 a bound pyrrole product in the latter system could act in a redox non-innocent fashion.…”