A chemoselective Reformatsky-Negishi approach to α-haloaryl esters

A practical synthesis of alpha-haloaryl esters has been achieved via a chemoselective Negishi coupling of poly-halogenated aromatics and Reformatsky reagents in the presence of catalytic Pd(dba)(2) and Xantphos. This chemistry tolerates a variety of aryl halides and was successfully applied to the synthesis of Ibuprofen. The alpha-haloaryl ester products, exemplified by ethyl 2-(4-bromo-2-chlorophenyl)acetate (3a), can be further functionalized via palladium or copper catalysis to afford an array of a-aryl esters. (C) 2014 Elsevier Ltd. All rights reserved.