A decarboxylative approach for the regioselective hydroarylation of alkynes

A decarboxylative approach for the regioselective hydroarylation of alkynes 

Zhang, J.; Shrestha, R.; Hartwig, J. F.; Zhao, P. Nature Chem. 2016, 94, 1144-1151.

–North Dakota State University, UC Berkeley

Abstract: 
Regioselective activation of aromatic C–H bonds is a long-standing challenge for arene functionalization reactions such as the hydroarylation of alkynes. One possible solution is to employ a removable directing group that activates one of several aromatic C–H bonds. Here we report a new catalytic method for regioselective alkyne hydroarylation with benzoic acid derivatives during which the carboxylate functionality directs the alkyne to the ortho-C–H bond with elimination in situ to form a vinylarene product. The decarboxylation stage of this tandem sequence is envisioned to proceed with the assistance of an ortho-alkenyl moiety, which is formed by the initial alkyne coupling. This ruthenium-catalysed decarboxylative alkyne hydroarylation eliminates the common need for pre-existing ortho-substitution on benzoic acids for substrate activation, proceeds under redox-neutral and relatively mild conditions, and tolerates a broad range of synthetically useful aromatic functionality. Thus, it significantly increases the synthetic utility of benzoic acids as easily accessible aromatic building blocks.