Synthesis of 2-(Trifluoromethyl)indoles via Domino Trifluoromethylation/Cyclization of 2-Alkynylanilines

Org Lett. 2018 Mar 16;20(6):1676-1679. doi: 10.1021/acs.orglett.8b00509. Epub 2018 Feb 28.

Abstract

A new method for the synthesis of 2-(trifluoromethyl)indoles using easily accessible 2-alkynylanilines and a well-established fluoroform-derived CuCF3 reagent is described. This method utilizes a domino trifluoromethylation/cyclization strategy to construct the indole cores with no ambiguity of the CF3 position. The intriguing 3-formyl-2-(trifluoromethyl)indoles can also be synthesized by this protocol, which are useful intermediates for the preparation of trifluoromethylated drug analogues. The ultimate CF3 source is the inexpensive industrial byproduct fluoroform.

Publication types

  • Research Support, Non-U.S. Gov't