General and selective syn-carboxylation-trifluoromethylation of terminal alkynes: application to the late-stage modification of dehydrocholic acid.

Abstract

A general and selective method is developed that allows difunctionalization of terminal alkynes by a Cu(iii)-CF3 complex and a carboxylic acid regioselectively and with unusual syn-stereochemistry. This method is broadly applicable to various carboxylic acids and terminal alkynes, producing a range of biologically active trifluoromethyl enol carboxylic esters. The synthetic potential of this method is further demonstrated by the late-stage functionalization of a complex pharmaceutical compound dehydrocholic acid.