Mechanistic Study of Transition-Metal-Catalyzed Carbon-Carbon Bond Formation

Abstract

Transition-metal-catalyzed cross-coupling reactions (CCRs) have emerged as a powerful synthetic tool for the construction of carbon-carbon bonds, allowing a wide range of coupling partners to be combined efficiently. However, although some mechanistic experiments are performed, the detailed mechanisms of these transformations remain poorly understood. Quantum mechanical calculations were used to investigate the mechanism of transition-metal-catalyzed CCRs, leading to a deeper understanding of the molecular-level interactions in catalytic cycles to design new transformations. Specifically, DFT calculations were used to study in detail the mechanism of C-C bond formation in Ni diketonate-based catalytic systems (Chapter 1), showing the anionic ligand could be beneficial to the application of the steric radical in the CCRs to form quaternary center in the products. With this study in hand, the mechanism of fluorine-containing (vs nonfluorinated counterpart) decarboxylative C-C bond formation was explored, rationalizing the different reactivity for fluorinated system and nonfluorinated system (Chapter 2). With the molecular-level understanding of these reactions, optimized experiment conditions were used to promote the formation of the fluorinated products. Iron has been recognized as an economically and environmentally attractive transition metal catalyst. In particular, iron complexes have been demonstrated as powerful synthetic methods in the C-C bond formation. In Chapter 3, I used DFT and DLPNO-CCSD(T) calculations to investigate the nature of iron-catalyzed C-H allylations, unraveling the role of the ligand and the reaction pathways in this reaction. Computational studies revealed that the underlying allylation reaction pathway is consistent with an inner-sphere radical reaction mechanism, which involves the partial dissociation and rotation of the bisphosphine ligand. Finally, a dearomatization of Asmic isocyanides was studied computationally, implicating an electron transfer-initiated sequence that triggers an isocyanide rearrangement followed by radical-radical anion coupling to form the cyclohexadiene product (Chapter 4). This work shows the detailed mechanism of this dearomatization-dimerization-dislocation of Asmic isocyanides reaction, which provide a foundation for the synthesis of cyclohexadiene product.