Mechanisms and stereoselectivities of phosphine-catalyzed Rauhut-Currier reaction between N-phenylmaleimide and 2-benzoyl acrylate: A computational investigation

Abstract

With the aid of density functional theory (DFT) calculations, we have studied the mechanisms and stereoselectivities in PPh3-catalyzed intermolecular Rauhut-Currier reaction of N-phenylmaleimide (R1) and 2-benzoyl acrylate (R2). Various reaction pathways in the absence and presence of benzoic acid (PhCO2H) were investigated. Comparing the overall reaction barriers based on mechanism A (in the absence of PhCO2H) and mechanism B (in the presence of PhCO2H), we were able to understand the critical role of PhCO2H. The preferred mechanism (mechanism B) initiates nucleophilic conjugated addition of PPh3 to R1 to form a zwitterionic intermediate B_1 (first step). It then reacts with R2 to generate intermediate B_2 (second step). The following intramolecular proton transfer is shown to occur via two successive H-shift processes with the assistance of PhCO2H: the C5 atom of B_2 first abstracts a proton from PhCO2H to generate B_3, then the H atom transfers from C3 to the PhCOO− group completes the intramolecular proton transfer and produces B_4 (third step). Finally, the catalyst PPh3 releases from B_4 affording the cross-coupling product (fourth step). On the basis of our calculation results, path D leading to the S-configuration product P(S) is the most energy favorable pathway among the eight possible stereoselective pathways. The second step is found to be the rate- and stereoselectivity-determining step with an overall free energy barrier of 21.3kcal/mol. Our DFT results are in good agreement with experimental observations. The present study should be valuable for understanding this kind of reaction.