Theoretical Analysis of the Mechanism of Palladium(II) Acetate-Catalyzed Oxidative Heck Coupling of Electron-Deficient Arenes with Alkenes: Effects of the Pyridine-Type Ancillary Ligand and Origins of the meta-Regioselectivity

Abstract

A systematic theoretical study is carried out on the mechanism for Pd(II)-catalyzed oxidative cross-coupling between electron-deficient arenes and alkenes. Two types of reaction pathways involving either a sequence of initial arene C-H activation followed by alkene activation, or the reverse sequence of initial alkene C-H activation followed by arene activation are evaluated. Several types of C-H activation mechanisms are discussed including oxidative addition, σ-bond metathesis, concerted metalation/deprotonation, and Heck-type alkene insertion. It is proposed that the most favored reaction pathway should involve an initial concerted metalation/deprotonation step for arene C-H activation by (L)Pd(OAc)(2) (L denotes pyridine type ancillary ligand) to generate a (L)(HOAc)Pd(II)-aryl intermediate, followed by substitution of the ancillary pyridine ligand by alkene substrate and direct insertion of alkene double bond into Pd(II)-aryl bond. The rate- and regio-determining step of the catalytic cycle is concerted metalation/deprotonation of arene C-H bond featuring a six-membered ring transition state. Other mechanism alternatives possess much higher activation barriers, and thus are kinetically less competitive. Possible competing homocoupling pathways have also been shown to be kinetically unfavorable. On the basis of the proposed reaction pathway, the regioselectivity predicted for a number of monosubstituted benzenes is in excellent agreement with experimental observations, thus, lending further support for our proposed mechanism. Additionally, the origins of the regioselectivity of C-H bond activation is elucidated to be caused by a major steric repulsion effect of the ancillary pyridine type ligand with ligands on palladium center and a minor electronic effect of the preinstalled substituent on the benzene ring on the cleaving C-H bond. This would finally lead to the formation of a mixture of meta and para C-H activation products with meta products dominating while no ortho products were detected. Finally, the multiple roles of the ancillary pyridine type ligand have been discussed. These insights are valuable for our understanding and further development of more efficient and selective transition metal-catalyzed oxidative C-H/C-H coupling reactions.

Ohne dirigierende Gruppen: übergangsmetallkatalysierte C‐H‐Aktivierung einfacher Arene

“…Denn vermutlich rufen nicht nur die elektronischen Eigenschaften der Substrate, sondern auch der Raumbedarf des Liganden die beobachtete Regioselektivität hervor. [74] In ähnlicher Weise berichteten auch Sanford und Mitarbeiter kürzlich über den positiven Effekt von Pyridinliganden auf Geschwindigkeit und Selektivität oxidativer Kupplungen zwischen einfachen Arenen und Acrylaten. [75] Anhand von oXylol als Modellsubstrat wurde dabei der Einfluss der Ligandeneigenschaften auf die Regioselektivität der Reaktion gezeigt (Schema 17).…”

Computational Studies of Heteroatom‐Assisted CH Activation at Ru, Rh, Ir, and Pd as a Basis for Heterocycle Synthesis and Derivatization

“…Reprotonation then facilitates N-decoordination of the MPAA ligand, and this is thought to facilitate the functionalization steps (modeled with ethylacrylate). A related study by Zhang and coworkers considered monosubstituted arenes [47].…”

Mechanistic study on the regioselectivity of Co-catalyzed hydroacylation of 1,3-dienes

“…Computational studies were performed with Gaussian 09 program [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Geometry optimization was conducted in gas phase with M06 method [24].…”