Organocatalytic kinetic and dynamic kinetic resolutions of alcohols

Abstract

The overall aim of this thesis is to explore new protocols for the isothiourea-catalysed acylative kinetic resolution of challenging alcohols and new dual-catalytic systems for the dynamic kinetic resolution of secondary and tertiary alcohols.

Initially, in Chapter I, the concept of kinetic resolution and its application to the acylation of alcohols using non-enzymatic catalysts is described, with reference to the current state-of-the-art, to place the work of this thesis in the context of the literature.

In Chapter II, the development of a kinetic resolution of challenging aryl alkenyl secondary alcohols by enantioselective esterification using the isothiourea HyperBTM as a catalyst is described. A new protocol has been developed and demonstrated for a range of substrates. The utility of the process is exemplified by its application to monomers derived from biomass resources for the preparation of synthetically valuable chiral molecules.

The second part of this thesis aims to find a new protocol for performing a novel, challenging, non-enzymatic dynamic kinetic resolution of racemic secondary alcohols. Chapter III delineates the advantages of using dynamic kinetic resolution for the enantioselective acylation of alcohols, reviews current literature precedent, and highlights important unsolved challenges.

In Chapter IV, a range of metal catalysts that can promote the racemisation of secondary alcohols, through a reversible dehydration mechanism, are discussed, followed by their applications to a new dual-catalytic dynamic kinetic resolution in combination with an isothiourea-catalysed enantioselective acylation.

Finally, in Chapter V, a number of catalytic systems are investigated for the racemisation of tertiary alcohols. Preliminary studies into the highly challenging dual-catalytic dynamic kinetic resolution of tertiary alcohols are also discussed, which represents efforts towards solving a significant milestone in the field of asymmetric catalysis.

Date of Award	26 Jun 2019
Original language	English
Awarding Institution	University of St Andrews
Supervisor	James Taylor (Supervisor) & Andrew Smith (Supervisor)