Forging chiral quaternary stereocenters from simple and readily available starting materials under mild reaction conditions continues to be among the most challenging and attractive research goals in modern synthetic chemistry. Since the early seminal work by Tsuji and Trost, there has been rapid progress in the development of chiral ligands and scope of the electrophilic and nucleophilic reaction partners used in Pd-catalyzed allylic substitution reactions over the past few decades. Despite the numerous advances already realized, building chiral branched allylic derivatives from simple and readily available starting materials continues to be an important task in synthetic chemistry, due to the potential of these chiral allylic compounds in post-synthetic campaigns. Allylic scaffolds bearing quaternary stereocenters based on Pd-catalyzed allylic substitution reactions still remain rather underexplored.
The main goal of this thesis was the development of new catalytic systems and novel chiral ligands for the Pd-catalyzed regio- and enantioselective synthesis of more sterically challenging a,a-disubstituted allylic compounds. Furthermore, gaining insight into the details of the reaction mechanism to reveal the origin of the regio- and enantioselectivity would be much desired. In this context, the following objectives are pertinent to the content of this thesis: 1) Developing a concise, efficient, regio- and enantioselective synthesis of various enantioenriched a,a-disubstituted allylic amines, including both aryl- and alkyl-substituted derivatives; 2) To unlock the origin of the regio- and enantioselectivity in the asymmetric allylic aminatrion by density functional theory (DFT) calculations in combination with mechanistic control experiments; 3) Design new methodology that enables the regio- and enantioselective synthesis of chiral allylic sulfones featuring quaternary stereocenters, and the utilization of such methodology in the synthesis of natural compounds.