Theoretical Analysis of Factors Controlling Pd-Catalyzed Decarboxylative Coupling of Carboxylic Acids with Olefins

Transition-metal-catalyzed decarboxylative coupling presents a new and important direction in synthetic chemistry. Mechanistic studies on decarboxylative coupling not only improve the understanding of the newly discovered transformations, but also may have valuable implications for the development of more effective catalyst systems. In this work, a comprehensive theoretical study was conducted on the mechanism of Myers' Pd-catalyzed decarboxylative Heck reaction. The catalytic cycle was found to comprise four steps: decarboxylation, clef in insertion, beta-hydride elimination, and catalyst regeneration. Decarboxylation was the rate-limiting step, and it proceeded through a dissociative pathway in which Pd(II) mediated the extrusion of CO2 from an aromatic carboxylic acid to form a Pd(II)-aryl intermediate. Further analysis was conducted on the factors that might control the efficiency of Myers' decarboxylative Heck reaction. These factors included Pd salts, ligands, acid substrates, and metals. (1) Regarding Pd salts, PdCl2 and PdBr2 were worse catalysts than Pd(TFA)(2), because the exchange of Cl or Br by a carboxylate from Pd was thermodynamically unfavorable. (2) Regarding ligands, DMSO provided the best compromise between carboxyl exchange and decarboxylation. Phosphines and N-heterocarbenes disfavored decarboxylation because of their electron richness, whereas pyridine ligands disfavored carboxyl exchange. (3) Regarding acid substrates, a good correlation was observed between the energy barrier of R-COOH decarboxylation and the R-H acidity. Substituted benzoic acids showed deviation from the correlation because of the involvement of pi(substituent)-sigma(C-ipso-Pd) interaction. (4) Regarding metals, Ni and Pt were worse catalysts than Pd because of the less favorable carboxyl exchange and/or DMSO removal steps in Ni and Pt catalysis.