Palladium-Catalyzed Hydroarylation of Propiolamides. A Regio- and Stereocontrolled Method for Preparing 3,3-Diarylacrylamides

Abstract

A general regio- and stereoselective synthesis of 3,3-diarylacrylamides is reported. Palladium-catalyzed coupling reactions of propiolamides with aryl halides provide arylpropiolamides. A subsequent hydroarylation reaction of these arylpropiolamides with aryl halides, catalytic palladium, an amine base, and formic acid in refluxing ethyl acetate provides 3,3-diarylacrylamides regio- and stereoselectively. The unique stereo- and regiocontrol is presumed to proceed through careful reaction parameters that allow intramolecular coordination of the propiolamide amide functionality to the transient palladium−alkyne complex. Palladium-catalyzed hydroarylation of propiolamides has not been studied; however, preliminary results from related systems suggest that regioselective addition can be achieved. The methodology as a synthesis tool is demonstrated in an efficient route to previously difficult-to-prepare potent, benzimidazole antiviral targets. In addition, the synthesis scope is explored where, by judicious c...