Enantioselective syntheses of 2,3-dihydro-4h-pyran-4-ones and 3(2h)-furanones
This thesis concerns the construction of 2,3-dihydro-4r7-pyran-4-one and 3(2//)-furanone ring systems by mercury(II)-catalysed reactions, or by more conventional cyclisations, and the potential of such reactions for the synthesis of natural products. Chapter one provides a literature survey of reactions permitting the construction of 2,3-dihydro-4/7-pyran-4-one and 3(2//)-furanone ring systems background literature to relevant natural products is also provided, such as polyether antibiotics, carbohydrates and antitumer agents. Chapter two describes the application of mercury(II)-catalysed cyclisations of dihydroxylated ynones to give 3(2//)-furanones this was achieved by the dihydroxylation of enynones using Sharpless's asymmetric dihydroxylation conditions followed by treatment with a mecury(II) catalyst. The scope and limitations of this method were investigated and shown in several cases to give good yields and high enantiomeric excess. In cases where there was an electron-donating group on the alkyne functionality, such as an ethoxy group, the cyclisation occurred spontaneously during the dihydroxylation step. This methodology was applied for the synthesis of a natural product to confirm the selectivity of the cyclisation step. In chapter three the reactions developed in chapter two formed the basis of a proposed route to the natural product (-)-Pestalotin, a gibberellins synergist. Thus, the Sharpless asymmetric dihydroxylation method was applied to (3,y-unsaturated ketones to give a main intermediate for the synthesis. Chapter four details different approaches to NK10958P, a plant growth regulator. The synthesis of two main fragments was achieved and the coupling of these fragments by syn-selective aldol addition is expected to furnish NK10958 P and its methyl analogue, pironetin, which has been reported to have good cytotoxic and immunosuppressive activity. Full experimental details follow chapter 2-4 and reference sections are provided at the end of each chapter.