Nucleophilic C–H Etherification of Heteroarenes Enabled by Base-Catalyzed Halogen Transfer

Abstract

We report a general protocol for the direct C-H etherification of <i>N</i>-heteroarenes. Potassium <i>tert</i>-butoxide catalyzes halogen transfer from 2-halothiophenes to <i>N</i>-heteroarenes to form <i>N</i>-heteroaryl halide intermediates that undergo tandem base-promoted alcohol substitution. Thus, the simple inclusion of inexpensive 2-halothiophenes enables regioselective oxidative coupling of alcohols with 1,3-azoles, pyridines, diazines, and polyazines under basic reaction conditions.