Catalytic enantioselective acyl transfer for the synthesis of atropisomers
Abstract
This thesis details the development of enantioselective, isothiourea-catalysed, acyl-transfer
methodology for the synthesis of atropisomers.
Chapter 1 aims to introduce organocatalysis in the context of the current state-of-the art in Lewis
base catalysis and its application in enantioselective acyl transfer. Following this, the importance
of axial chirality and the current art in the synthesis of biaryl and non-biaryl atropisomers is
introduced. The potential for isothiourea catalysis to provide a new platform in this area is then
outlined.
Chapter 2 outlines development of methodology for the acylative desymmetrisation of biaryl
phenols. After optimisation of the desymmetrisation of a model system, computational and
experimental techniques were used to probe the selectivity and mechanism of the process. The
methodology was then extended to a scope of 14 biaryl substrates, providing highly
enantioenriched products (up to 98:2 er, 54% isolated yield). Discussion of the mechanism of
their formation, and the enantioselectivity of the process is also provided.
Chapter 3 outlines attempts to extend the methodology developed in chapter 2 to the synthesis
of molecules with a C–N stereogenic axis. The synthesis of several target biaryl heterocycle
substrates was attempted and tentative attempts to adapt current acyl transfer methodology to
these species is described. Additionally, the synthesis of atropisomeric anilides via N-acylation of
secondary anilines is detailed.
Chapter 4 contains a summary of the work that has been carried out for this thesis and the
potential extensions to future work within the field of Lewis base organocatalysis.
Chapter 5 provides the experimental details for the synthesis of the compounds which are
contained in this thesis, as well as the associated analytical data for their characterisation.
Type
Thesis, PhD Doctor of Philosophy
Rights
Embargo Date: 2022-02-10
Embargo Reason: Thesis restricted in accordance with University regulations. Print and electronic copy restricted until 10th February 2022
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Description of related resources
Data underpinning Elizabeth Sarah Munday's thesis. Munday, E.S., University of St Andrews. DOI: https://doi.org/10.17630/86f9965a-ce9b-4222-bba5-5bd923f2331eRelated resources
https://doi.org/10.17630/86f9965a-ce9b-4222-bba5-5bd923f2331eItems in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.