Synthesis of CF3-Substituted N-Heterocyclic Compounds Based on C-H Activation-Initiated Formal [2 + 3] Annulation Featuring with a Latent Nucleophilic Site.

ABSTRACT

Presented herein is a novel synthesis of CF3-substituted pyrrolo[1,2-a]indole derivatives based on the cascade reactions of N-alkoxycarbamoyl indoles with CF3-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.