Palladium-catalyzed asymmetric allylic amination. Developpment and synthetic applications

Identifier:  TDX:2518

Handle: https://hdl.handle.net/20.500.11797/TDX2518

Authors:  Soriano Istat, Sebastien

Abstract:
This PhD work is to apply it in the synthesis of different natural products or analogues, as well as to enlarge the usefulness of this methodology to new substrates and new nucleophiles. In connection with this purpose, the specific objectives of this thesis are the following: 1) Enantioselective synthesis of Cidofovir analogues. The research described in this part aims to develop an asymmetric and regioselective metal-catalyzed allylic amination processes using purinic and pyrimidinic bases and palladium catalysts, and the application of the previous method to the synthesis of acyclic nucleosides analogues of Cidofovir. 2) Enantioselective synthesis of nectrisine, Enantioselective synthesis of fagomine. The work presented in this section has as a final objective the enantioselective synthesis of nectrisine starting from the key synthon allylamine prepared through an palladium-catalyzed Dynamic Kinetic Asymmetric Transformation (DYKAT) of racemic vinyloxirane using imido nucleophiles. 3) Enantioselective synthesis of fagomine. Aiming to explore the synthesis of allyl amine from allylic carbonate using palladium catalysts, and taking into account the role of DACH Trost ligands in the control of the regioselectivity, we wondered whether structural elements in the substrate able to provide hydrogen bonding could bias the regiochemistry of palladium-catalyzed allylic amination of allylic electrophile to afford branched derivatives. To continuation, apply this methodology to a short enantioselective formal synthesis of fagomine, an iminosugar that shows activity against mammalian gut α-glucosidase and β-galactosidases.4) A final objective of the Thesis was to explore the use of the catalytic system Pd/ Trost ligand with different imido and imidocarboxylate nucleophiles. The different products obtained in this study were used as starting materials in the synthesis of valuable different compounds such as lactam, lactone and 4-amino-4-deoxy sugar.