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

Thomas R. Puleo, Danielle R. Klaus, Jeffrey S. Bandar

2021Journal of the American Chemical Society31 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

ChemistryHalogenRegioselectivityCatalysisHalideNucleophilic substitutionBase (topology)AlcoholNucleophilic aromatic substitutionNucleophileCombinatorial chemistryMedicinal chemistryOrganic chemistryMathematicsMathematical analysisAlkylCatalytic C–H Functionalization MethodsSynthesis and Catalytic ReactionsSulfur-Based Synthesis Techniques
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