Straightforward access to C2-formyl indoles using an oxidative combination of N-chlorosuccinimide and dimethyl sulfoxide

Abstract

C2-formyl indoles are important building blocks for the organic synthesis of alkaloids and small molecules with broad biological activities. Generally, its preparation involves both direct formylation of indoles at the activated C2-position with as unstable carbonyl sources and oxidative cleavage of tedious prepared tetrahydro-β-carbolines (THβCs) in the harsh conditions. In continuation of our research on the oxidative functionalization of indoles, in this letter, we report that straightforward effectively oxidation of easily available 2-methylindoles bearing C3-heteroatom functional group proceeds regioselectively C2-formyl indoles in good and excellent yields employing an oxidative combination of NCS/DMSO. This methodology presents a reasonably broad substrate scope and excellent functional group tolerance, thus enabling the preparation of highly versatile building blocks susceptible to further functionalization. An additional feature of this approach includes high efficiency, ease of operation, facile purification, and short reaction time, making it a promising strategy for organic synthesis and drug discovery.