A decarboxylative approach for regioselective hydroarylation of alkynes

Nat Chem. 2016 Dec;8(12):1144-1151. doi: 10.1038/nchem.2602. Epub 2016 Sep 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't