Novel methodologies for the synthesis and characterization of sulfinamides and vinyl esters

Abstract

The first chapter of this thesis begins by introducing methods for determining enantiopurity, followed by an in-depth discussion of how three-component self-assembly reactions between an amine, a chiral analyte, and 2-formylphenyl boronic acid (2-FPBA) can be used to produce stable iminoboronate ester (IBE) complexes. The extensive use of these three-component IBE assemblies for determining the enantiomeric excess of a range of chiral analytes using various analytical methods is discussed. A detailed review of the growing popularity of these supramolecular assembly motifs for formation of supramolecular stimuli-responsive materials and for the orthogonal derivatization of biomolecules is also described.

Chapter 2 describes how 1H NMR spectroscopic analysis of IBE complexes derived from 2-FPBA, tert-butanesulfinamide, and BINOL revealed previously unknown concentration- and enantiopurity-dependent anisotropic effects. Unlike previous IBEs, decreased N→B coordination in BINOL-derived sulfinamide-IBE complexes results in their significant aggregation in solution. These aggregates contain mixtures of homochiral and heterochiral complexes, which means that chemical shift values in their 1H NMR spectra are dependent on the enantiopurity of the parent chiral sulfinamide, giving rise to a phenomenon termed in this thesis diastereomer aggregation-induced anisotropy (DAIA).

Chapter 3 describes the optimisation of a new stepwise Bull-James protocol for accurately measuring the enantiopurity of chiral sulfinamides using three-component complexes derived from chiral pinanediol and 2-FPBA. This derivatisation approach affords a highly reliable protocol to determine the enantiomeric excess of a wide range of sulfinamides by 1H NMR spectroscopic analysis. Use of a fluorinated 2-FPBA template also enables the enantiomeric excess of chiral sulfinamides to be determined by 19F NMR spectroscopic analysis. Preliminary results on development of a new Bull-James derivatisation protocol to determine the enantiomeric excess of sterically-demanding α-quaternary amines are also described.

The fourth chapter describes investigations into using N-oxides (e.g. dimethylaminopyridine-N-oxide) as catalysts in Baeyer-Villiger (BV) oxidation reactions of ketones and α,β-unsaturated ketones for the efficient production of esters and vinyl esters. Mechanistic studies have revealed that N-oxides act as proton and phase-transfer catalysts in the BV oxidation reactions of electron-rich ketones. These N-oxides function to accelerate nucleophilic delivery of mCPBA to the ketone carbonyl, whilst also suppressing epoxidation reactions of vinyl ester products. The discovery that N-oxides can catalyse degradation of the mCPBA oxidant resulted in trimethylamine N-oxide being identified as an improved 2nd generation catalyst for the BV oxidation of α,β-unsaturated ketones.

Date of Award	8 Sept 2021
Original language	English
Awarding Institution	University of Bath
Supervisor	Steven Bull (Supervisor) & Christopher Pudney (Supervisor)