Metal-free regio- and stereoselective vicinal difunctionalisation of dienyl carbamates

Identifier:  TDX:2986

Handle: https://hdl.handle.net/20.500.11797/TDX2986

Authors:  Giménez Nueno, Irene

Abstract:
The present PhD work aimed at developing new synthetic methodologies for the regio- and stereoselective preparation of 1-amino-2-heteroatom-but-3-ene-1,2-diyl scaffolds as common structural motifs in relevant lipids occurring in nature. The proposed retrosynthetic pathway involved the formation of a key vinylaziridine intermediate from readily available dienols, followed by ring-opening with different nucleophilic sources to give access to 3-heterosubstituted sphingosine analogues. With this objective in mind, we have developed a sequential metal-free PhIO mediated intramolecular aziridination/ring-opening of dienyl carbamates and subsequent organocatalysed kinetic resolution of racemic oxazolidinone intermediates that gave access to enantioenriched 1,2-difunctionalised products that could be further elaborated via cross-metathesis. Alternatively, the asymmetric aziridination of dienyl carbamate in the presence of chiral hypervalent iodine reagents has been studied for the preparation of vicinal oxyaminated compounds with promising results. In addition, the last part of the present PhD work describes the research carried out during a predoctoral stay at UC Berkeley under the supervision of Prof. R. Sarpong, aiming at the total synthesis of phleghenrine alkaloids for the biological evaluation as palliative drugs for Alzheimer’s disease. The proposed retrosynthetic pathway envisioned the formation of the phleghenrine [3.2.2] bicyclic core via an Inverse-Electron Demand Diels-Alder reaction. Therefore, a Lewis acid-promoted protocol for the regio- and stereoselective preparation of different substituted bicyclo [3.2.2] nonanes using pyridotropone as a diene and a set of electron-rich dienophiles has been developed.