Over the last 50 years, remarkable progress has been made in TM-catalyzed allylic substitution reactions testified by the significant potential in the rapid and cost-effective synthesis of natural products, pharmaceuticals, and functional materials. Current research in the area of “allylic chemistry” is mainly focused on maturing the regio-, stereo-, and enantio-selective features combined with the development of new ligands, allylic precursors, advancing mechanistic studies and more elaborate synthetic applications. This doctoral thesis is mainly focused on the development of novel catalytic (domino) synthesis methods based on Pd-catalyzed allylic substitution for the stereoselective synthesis of functional small molecules and heterocycles utilizing a detailed ligand engineering and substrate design. The scope of this thesis is organized into five chapters: the first chapter is a general introduction on the regular aspects of allylic chemistry. The second chapter illustrates the first general method for the preparation of enantioenriched tertiary allylic aryl ethers through a Pd-catalyzed regio- and enantio-selective etherification of VCCs in the presence of phenolic nucleophiles. The regioselectivity of the reaction can be finely tuned to the Z-selective linear product by switching the phosphoramidite ligand to a monophosphine ligand, thus proving the crucial role of proper ligand engineering. The third chapter describes a newly designed tertiary allylic alcohol equipped with a carboxyl group, which is firstly used for α,β-unsaturated γ-lactams synthesis through Pd-catalyzed stereoselective allylic amination and intramolecular cyclization process. Mechanistic studies suggest that the carboxyl group is crucial for this transformation, and acts as an activating and stereodirecting functional group. The fourth chapter presents a ligand-controlled stereodivergent approach for the synthesis of either Z or E-configured γ-amino acids derived from tertiary allylic alcohols and secondary amines. The experimental results highlight the crucial role of the supporting ligand and the diphosphine bite angle. The fifth chapter reports a general method for substituted unsaturated caprolactam synthesis through a cascade amination/cyclization process using vinyl γ-lactones as substrate by using a newly developed phosphoramidite ligand. Finally, a general conclusion for each chapter is given and potential applications for these developed methodologies are also discussed.
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