Advances in the Mechanistic Landscape of Pd-Catalyzed C-H Activation and Functionalization: A Synergy of Computation and Experiment

Abstract:

Pd-catalyzed C-H bond activation has greatly revolutionized the field of organic synthesis over the past two decades. A deep mechanistic understanding of this process is crucial for the rational design of new reactions. This review summarizes recent advances in the combination of experimental and computational approaches toward understanding Pd-catalyzed C-H bond activation mechanisms. Density Functional Theory (DFT) serves as a key tool for studying the mechanisms of organic reactions. In this review, a range of mechanistic pathways for Pd-catalyzed C-H bond activation and functionalization reactions were described. The widely recognized concerted metalation and deprotonation pathway, which occurred through a monometallic Pd complex or a bimetallic PdAg complex with acetate/amidate as the base, was highlighted. Oxidative addition, carbometalation and elimination, electrophilic aromatic substitution, and σ-bond metathesis, along with 1,2-addition, were also included. This paper presents a systematic framework for understanding the mechanisms of Pd-catalyzed C-H bond activation, offering valuable insights for researchers engaged in mechanistic studies and reaction development in this field.