Stereospecific Synthesis of Tri- and Tetrasubstituted α-Fluoroacrylates by Mizoroki-Heck Reaction.

Org Lett

Normandie Univ, COBRA, UMR 6014 & FR 3038; Univ Rouen; INSA Rouen; CNRS, IRCOF, 1 rue Tesnière 76821 Mont-Saint-Aignan Cedex, France.

Published: February 2016

Ligand-free, efficient, palladium-catalyzed Mizoroki-Heck reaction between methyl α-fluoroacrylate and arene or hetarene iodides is reported for the first time. The reaction is stereospecific and provides fair to quantitative yields of fluoroalkenes. The Mizoroki-Heck reaction starting from more hindered and usually reluctant trisubstituted acrylate, to access tetrasubstituted fluoroalkenes, is also reported. Finally, the use of a three-step synthesis sequence, including Mizoroki-Heck reaction, allows the synthesis of fluorinated analogues of therapeutic agents with high yield.

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http://dx.doi.org/10.1021/acs.orglett.5b03571DOI Listing

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