Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748763
Title: The development of catalytic enantioselective additions to imines
Author: Robertson, Gerard Phillip
ISNI:       0000 0004 7232 0062
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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Abstract:
This thesis describes the development and application of catalytic enantioselective additions to imines. Chapter 2 describes the application of bifuntional iminophosphorane (BIMP) organosuperbases, which are a novel class of bifunctional organocatalyst developed in the group to the first 'unactivated' ketimine phospha-Mannich reaction of diethyl phosphite to afford α- aminophosphonic acid derivatives in excellent yields and moderate enantiocontrol (>99% yield, up to 71% ee). Chapter 3 describes the first silver-catalysed enantioselective Mannich reaction of diazoacetates to NBoc protected aldimines. The reaction proved to be broad in scope with respect to the aldimine; with 14 aromatic aldimines reported and variability on the diazoacetate was also tolerated, giving products with good yields (60-86%) and with very high levels of enantioselectivity (88-98% ee) under the control of the bisphosphine ligand, DM-Segphos. The reaction proved to be scalable as demonstrated on a 5.0 mmol scale with a 1 mol% catalyst loading with respect to silver triflate. The Mannich adduct was derivatised to a few useful products with retention of stereochemical configuration. NMR techniques and non-linear effects studies were used to analyse the catalytic system and gain an insight into the mechanism of this reaction. Chapter 4 describes efforts towards the first enantioselective Mannich reaction of ethyl diazoacetate to ketimines. The catalytic system used for this reaction was a modification of the one described in chapter 3, where BEMP was required as a base for reactivity, silver acetate and a chiral aminophosphine ligand made up the catalytic system. Although new reactivity was identified, catalytic turnover was plausibly hampered by reduction of the Ag(I) from the deprotonated diazoacetate. The Mannich adduct was formed in up to 47% yield and up to 42% ee. Chapter 5 describes the discovery of a novel, practical method for determining the longitudinal relaxation times of low γ 3 spin -1/2 nuclei which are scalar coupled to high γ 3 nuclei. The discovery of this method came about from mechanistic investigations into the catalytic system reported in chapter 3. The method makes it possible to extract T1 information for the insensitive low γ 3 nucleus from the EXSY spectrum of the observable high γ 3 nucleus. It is shown how the T1 relaxation constants of Ag can provide valuable insights into the geometrical properties of Ag-bisphosphine complexes. In principle, this method can be applied to any transition metal-ligand system and overcomes the limitations of conventional methods for T1 determination as it allows for the elucidation of T1 relaxation time constants of insensitive transition metal nuclei using standard NMR equipment.
Supervisor: Dixon, Darren J. Sponsor: Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.748763  DOI: Not available
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