Mechanistic Study of Manganese-Catalyzed C–H Bond Functionalizations: Factors Controlling the Competition between Hydroarylation and Cyclization

The Mn-catalyzed C–H functionalization of indoles with allenes developed by Rueping and co-workers provides an efficient access to various alkenylated indoles and substituted pyrroloindolones. Herein, we present a systematic computational study to understand the mechanism and origins of substrate-controlled chemoselectivity of the C–H functionalization reactions (hydroarylation vs cascade cyclization). For the disubstituted allene system, the computed mechanism consists of three main phases: C–H activation, allene migratory insertion, and protonation giving the hydroarylation product. All of these steps are feasible, in agreement with the good yield under the mild experimental conditions. On the other hand, for the trisubstituted allene system, hydroarylation is suppressed due to the higher energy barrier for the protonation step arising from the disfavored ligand–substrate steric repulsions between the carboxide ligand and the substituent group in the allene substrate; our computational results demonstrate that, after the allene insertion leading to a seven-membered cyclometalated intermediate, it undergoes a reaction pathway involving sequential “ketone to enol” isomerization, a 1,4-heteroaryl shift, and β-methoxyl elimination giving the pyrroloindolone product. In contrast, this isomerization → heteroaryl shift → β-methoxyl elimination process is unworkable in the disubstituted allene system, because the protonation step takes place more favorably owing to the lack of ligand–substrate steric interactions. The findings taken together give an insight into the role of the ligand–substrate interactions in directing the competitive pathways and differentiating the energies of key transition states by steric repulsions