Synthesis of CF<sub>3</sub>-Substituted <i>N</i>-Heterocyclic Compounds Based on C–H Activation-Initiated Formal [2 + 3] Annulation Featuring with a Latent Nucleophilic Site
Manqing Wang, Shengnan Yan, Bin Li, Huihang Hou, Chunhua Ma, Xinying Zhang, Xuesen Fan
Abstract
Presented herein is a novel synthesis of CF 3 -substituted pyrrolo[1,2- a ]indole derivatives based on the cascade reactions of N -alkoxycarbamoyl indoles with CF 3 -ynones. Mechanistically, the formation of a product involves a tandem process initiated by Rh(III)-catalyzed and N -alkoxycarbamoyl group-directed regioselective C2–H alkenylation of the indole scaffold followed by in situ removal of the directing group and intramolecular N -nucleophilic addition/annulation under one set of reaction conditions. To our knowledge, this is the first example in which a N -alkoxycarbamoyl unit initially acts as a directing group for C2–H functionalization of the indole scaffold and is then removed to provide the required reactive NH -moiety for subsequent intramolecular condensation. Moreover, the products thus obtained could be conveniently transformed into structurally and biologically attractive cycloheptenone fused indole derivatives through an acid-promoted cascade transformation. In addition, studies on the activity of selected products against human cancer cell lines demonstrated their potential as lead compounds for the development of novel anticancer drugs.