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Title: Investigating three component protocols to determine the enantiopurity of chiral amines and amino alcohols using 1H and 19F NMR spectroscopy
Author: Powell, Magdalena Elizabeth
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 2011
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Abstract:
This report describes the development of simple three-component chiral derivatisation protocols to determine the enantiopurity of a range of chiral amines and amino alcohols using IH and 19p NMR spectroscopic techniques. In each of the protocols described a 2-formylphenylboronic acid core participates in tandem imine formation with an amine moiety and boronate ester condensation with a chiral diol to afford a pair of diastereomeric imino-boronate esters. These derivatives show distinguishable resonances in NMR spectra; the relative integrals of which reflect the enantiopurity of the starting amine or amino alcohol. The first chapter commences with an introduction of the different methods available to scientists today to determine enantiopurity focusing primarily on assays that utilise NMR spectroscopic techniques and particularly those where chiral derivatising agents have been used. This shall be followed by a short overview of literature regarding nitrogen-boron interactions by means of an introduction to the history of the Bull/James group research, who have used this method to determine the enantiopurity of chiral amines, diols and diamines by a simple, quick chiral derivatisation protocol whereby a pair of diastereomers are formed that can be readily distinguished using I H NMR spectroscopy. The second chapter details the steps taken to establish a chiral derivatisation protocol to determine the enantiopurity of amino aIcohols (Scheme 1). Previous work in the group established that a silyl protection step of the hydroxyl moiety was necessary. The rest of the chapter informs about the selection of a chiral diol, methyl-2,3-dihydroxy-3-phenylpropionate 2, and the protocol's ability to determine the enantiopurity of a number of amino a1cohols is demonstrated. This protocol was even found to be successful when silyl-protected amino alcohols with remote stereocentres were used in a mixed solvent system. In the third and fourth chapters we report using a wide range of different boronic acids in protocols to determine the enantiopurity of a range of chiral amines, amino alcohols and diols. These boronic acids are based on the use of either 3-formylphenyl or 2-formylphenylboronic acids; with, the same tandem condensation reactions taking place to derivatise the parent compound. The boronic acids either contained novel moieties that had the potential to exhibit diagnostic resonances in IH NMR spectra or they contained a fluoro group which was designed to show distinct peaks in 19p NMR spectra. Distinct resonances (diagnostic or fluoro) corresponding to the individual diastereomers were observed and thus the relative integrals of their peaks allowed for the diastereomeric excess ( de) to be readily calculated, which, in turn, revealed the enantiomeric excess (ee) of the parent amine or amino alcohol (Scheme 2). 19p NMR spectroscopy was found to be a particularly useful tool as only two signals were produced that corresponded to each of the diastereomers formed and so there was no possibility of different resonances overlapping. However in some cases there was insufficient difference in chemical shift between the two resonances to be able to determine the enantiopurity of the starting amine successfully, which led to probing of the reagents to see if a better protocol could be established. x
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.579515  DOI: Not available
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