Mechanistic Studies On Palladium-Catalyzed Allylic Substitution Reactions

Chiral allylic alcohols,amines and sulfones are widely observed in many natural products and pharmaceutically relevant agents.The development of the efficient protocols for the construction of these compounds is highly important yet challenging in organic synthesis.Palladium-catalyzed allylic substitutions with O-,N-and Snucleophiles provide one of the most powerful approaches for the regio-and enantioselective synthesis of the tertiary C-O,C-N and C-S bonds.In this thesis,density functional theory calculations were performed to investigate the mechanisms of the palladium-catalyzed allylic substitutions.After the detailed reaction mechanisms estabilished,the origins of the regio-and enantioselectivities were unconvered.The present results should provide important insights for a better understanding of the related reactions and the design of new catalytic systems.The main contents of the dissertation are as follows:1.The detailed mechanistic investigation on the palladium/boron-catalyzed allylic substitution of vinylethylene carbonates with water was performed.The computations show that instead of the commonly accepted outer-sphere mechanism,the nucleophilic attack takes place via a novel type of inner-sphere pathway accompanied by the chelation between the hydroxyl group of the boronate moiety and the Pd center.The results indicate that branched product with(S)-configuration should be observed exclusively with this new mechanistic scenario,in line with the experimentallyobserved regio-and enantioselectivities.The enantioselectivity can be ascribed to the lone pair---π repulsive interaction between the O atom of the chelated hydroxyl group and the phenyl ring of ligand.2.DFT calculations were conducted to elucidate the mechanism of the palladiumcatalyzed regio-and enantioselective allylic substitution of allylic carbonates with benzyl amine.The C-N bond formation through the inner-sphere C-N reductive elimination via five-membered cyclic transition states was uncovered.The exclusive branched-regioselectivity was found to be dictated by the steric repulsion between the substrate and ligand.The combination of both lone pair---π repulsive interaction between the N atom of the nucleophile and the C-C double bond on the phenyl ring of ligand and dispersion interaction between ligand and substrate plays a dominant role in determining the enantioselectivity.3.The reaction mechanism of the palladium-catalyzed allylic substitution of allylic carbonates with sodium benzylsulfinate was investigated.A unique inner-sphere nucleophilic attack pathway via the six-membered cyclic transition states was revealed by means of DFT calculations,which was found to be assisted by the chelation of the O atom of the sulfonic group to the Pd center.It turns out that the regioselectivity is caused by the steric effect between the substrate and ligand.The C-H---O and C-H---πinteractions between the phenyl ring of nucleophile and the phosphoramidite ligand were found to account for the enantioselectivity.