Desymmetrisation reactions of cyclohexa-1,4-dienes

摘要

This thesis describes the development of diastereotopic group selective processes allowing the desymmetrisation of 1,4-cyclohexadiene derivatives and their application to target synthesis. Chapter 1 discusses some of the benefits that may be derived by the use of desymmetrisation, and demonstrates some of the ways in which it has recently been applied in compounds based on 1,4-cyclohexadiene. Chapter 2 describes a novel use of the Prins reaction to desymmetrise cyclohexadiene derivatives with high diastereoselectivity, and the optimisation of this resulting in an effective, practical and straightforward procedure. Chapter 3 details the investigation into desymmetrisation through diastereoselective iodocyclisation reactions, much higher stereoselectivity is observed than found previously in cyclohexadiene based substrates and an explanation is suggested by examination of structural differences. Chapter 4 reviews some of the previous synthetic approaches to members of the fawcettimine group of Lycopodium alkaloids. This is followed by the results of our first approach to the core tetracyclic ring system of lycoposerramine A, based on the discovery of a novel base induced diastereotoselective cyclisation reaction. Chapter 5 describes our revised approach, leading to the construction of a closely related tetracycle, although not permitting the construction of the target. Chapter 6 discusses the synthesis of the core tricyclic system of lycoposerramine S by a different strategy. NMR spectra obtained from the final product are found to closely match those obtained from the natural product.