Cathodically Coupled Electrolysis to Access Biheteroaryls

Abstract

An electrochemical approach to biheteroaryls through the coupling of diverse N-heteroarenes with heteroaryl phosphonium salts is reported. The reaction features pH and redox-neutral conditions and excellent regioselectivity, as well as exogenous air or moisture tolerance. Additionally, a one-pot, two-step protocol can be established to realize formal C−H/C−H coupling of heteroarenes, thereby greatly expanding the substrate availability. The utility of this method is demonstrated through late-stage functionalization, the total synthesis of nitraridine, and antifungal activity studies.B iheteroaryls constitute cardinal motifs in various natural products, ligands, agrochemicals, and pharmaceuticals (Scheme 1A). 1 Therefore, the construction of these scaffolds has received extensive attention (Scheme 1B). Classically, biheteroaryls are prepared via transition-metal-catalyzed crosscoupling approaches. 2 A number of alternative protocols toward challenging biheteroaryls have consequently been developed by capitalizing on C−H arylation processes, 3 cross-dehydrogenative couplings, 4 sulfur(IV)-mediated cross-