Meta-Selective Copper-Catalyzed C−H Arylation of Pyridines and Isoquinolines through Dearomatized Intermediates

Abstract

C(sp2)−H functionalization offers an efficient strategy for the synthesis of various elaborated N-containing heteroarenes. Along these lines, oxazino pyridines that can be readily prepared from pyridines, have been introduced as powerful substrates in radical- and ionic-mediated meta-C−H functionalization. However, the regioselective meta-C−H arylation of pyridines remains a great challenge. Herein, a copper-catalyzed meta-selective C−H arylation of pyridines and isoquinolines through bench-stable dearomatized intermediates is reported. Electrophilic aryl-Cu(III) species, generated from readily accessible aryl I(III) reagents, enable the efficient meta-arylation of a broad range of pyridines and isoquinolines. The method also allows the meta-selective alkenylation of these heteroarenes using the corresponding alkenyl I(III)-reagents. Late-stage arylation of drug-derived pyridines and larger-scale experiments demonstrate the potential of this synthetic methodology.