Catalyst-Controlled Chemoselective Reaction of 3-Indolylmethanols with Cyclic Enaminones Leading to C2-Functionalized Indoles

Abstract

A catalyst-controlled chemoselective formal 1,2-addition of 3-indolylmethanols with cyclic enaminones has been established in the presence of TfOH as a strong acid, which afforded C2-functionalized indole derivatives in generally good yields (up to 89% yield). This reaction not only confronted the great challenge in 1,2-addition of 3-indolylmethanols but also provided a good strategy for C2-functionalization of indole derivatives. The investigation on the reaction mechanism revealed that this formal 1,2-addition included a tandem sequence of 1,4-addition/[1,3]-C migration/isomerization, in which the [1,3]-C migration of the 1,4-addition product was a key step and the acidity of the catalyst played a decisive role in the observed chemoselectivity.