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

We report a general protocol for the direct C-H etherification of N-heteroarenes. Potassium tert-butoxide catalyzes halogen transfer from 2-halothiophenes to N-heteroarenes to form N-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.

Automated summary

A new method is reported for the direct C-H etherification of N-heteroarenes under basic conditions, using potassium tert-butoxide as a catalyst and 2-halothiophenes as a reagent for halogen transfer. This protocol allows for regioselective oxidative coupling of alcohols with a variety of N-heteroarenes, such as 1,3-azoles, pyridines, diazines, and polyazines.