211512-98-0Relevant academic research and scientific papers
Palladium-catalyzed hydroarylation of propiolamides. A regio- and stereocontrolled method for preparing 3,3-diarylacrylamides
Hay, Lynne A.,Koenig, Thomas M.,Ginah, Francis O.,Copp, James D.,Mitchell, David
, p. 5050 - 5058 (2007/10/03)
A general regio- and stereoselective synthesis of 3,3-diarylacrylamides is reported. Palladium-catalyzed coupling reactions of propiolamides with aryl provides 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 choice of reaction sequence and aryl iodide, either the Z- or E-geometric isomer of a given pair of 3,3-diarylacrylamides is independently prepared.
