SEAr-based reductive arylation of indoles with ketones: skeletal metamorphosis of ketones into aryl architectures

Abstract

We disclose for the first time the arylation of indoles with ketones in a reductive S_EAr manner (S_EAr: electrophilic aromatic substitution). The key to this achievement lies in the use of the following substrates: 1) an indole bearing an N-electron-withdrawing-group (EWG), 2) an indole bearing a C2-organic-functional-group (OFG), 3) a hybrid indole possessing an N-EWG and a C2-OFG, 4) 7-oxabicyclo[2.2.1]hept-5-en-2-one and its derivatives as ketones, and 5) a hydrosilane as a reducing agent. This reaction, catalyzed by a SiOTf (Si⁺) formed in situ from an indium salt and a hydrosilane, features a skeletal metamorphosis of the ketone into an aryl structure. Among synthetic applications of products, preliminary investigations revealed that 3-phenylindole, derived from the product N-EWG-3-phenylindole, undergoes skeletal editing into 4-phenylquinoline via a unique reaction pathway. A possible reaction mechanism was discussed and proposed based on the mechanistic studies.