Mild chlorodifluoroacylation of indoles via self-activation of sodium chlorodifluoroacetate

Abstract

A mild acylation of N-alkylindoles is reported using sodium chlorodifluoroacetate (SCDA) to synthesize useful chlorodifluoroketones. Friedel-Crafts reactivity of carboxylate salts is unusual and is not observed in similar electron-deficient acetate salts such as sodium trifluoroacetate. Mechanistic experiments indicate that the characteristic ability of SCDA to generate difluorocarbene is responsible for the reaction pathway via self-activation to form the active ester. © 2014 American Chemical Society.