Simple boronic acid based NMR protocols for determining the enantiomeric excess of chiral amines, hydroxylamines and diols

• Main Author: Tickell, David
• Other Authors: Bull, Steven ; James, Tony
• Published: University of Bath 2015
• Subjects: 543
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.687349

Three simple protocols for the determination of the enantiomeric excess of chiral amines, hydroxylamines and diols have been developed utilising boronic acid templates. In Chapter 1 some of the existing methods for determining the enantiomeric excess of chiral substrates have been reviewed including the use of chiral solvating agents, chiral derivatization agents, chiral gas chromatography, chiral HPLC, circular dichroism, UV-visible spectroscopy and fluorescence spectroscopy. In Chapter 2 the previous work by the Bull-James group is discussed along with the cited uses of our three-component derivatization protocols for determining the enantiomeric excess of chiral amines and diols. The syntheses of a range of α-arylglycines are described and their optical purities determined by a simple 1H NMR derivatization protocol. In Chapter 3 the first reported chiral derivatization protocol for determining the enantiomeric excess of chiral hydroxylamines by 1H NMR spectroscopy has been developed by formation of nitrono-boronate ester complexes whose structures have been confirmed by X-ray crystallography. A range of chiral hydroxylamines have been prepared and the mechanism for the conversion of a chiral amine to its corresponding hydroxylamine has been proposed by analysis of the side product formed during the final reaction step converting an oxaziridine to the desired hydroxylamine. In Chapter 4 the Horeau Principle is discussed and its applications in the literature reviewed. A new derivatization protocol based on this principle has been developed employing an achiral boronic acid template to form diastereomeric dimeric boronate complexes by its reaction with two equivalents of a chiral diol. The scope and limitations of this protocol have been determined and molecular modelling has been used to explain the differences in diastereomeric resonances observed for the boronate complexes formed.