Catalytic Enantioselective Lewis Base Chemistry: Solving the turnover problem
Lead Research Organisation:
University of St Andrews
Department Name: Chemistry
Abstract
The drive to reduce the environmental impact of the chemical sciences requires the development of efficient catalytic enantioselective methodologies to prepare enantiomerically pure compounds. Within this arena, the selective preparation of bespoke nitrogen heterocycles (such as indolines) is of widespread academic and industrial importance due to their privileged place as bioactive molecules and scaffolds for drug discovery. This project aims to develop versatile and state-of-the-art methodologies for the catalytic enantioselective synthesis of indolines and their derivatives using isothioureas as organocatalysts.
Background: We have previously shown that isothioureas promote a range of one-pot catalytic enantioselective cascade processes that rely upon the formation of a reactive ammonium enolate from readily available carboxylic acids. Although versatile, one drawback of this approach is that catalyst regeneration and turnover is promoted by intramolecular cyclisation (such as lactonisation). Building upon this work, this project will extend this process to the enantioselective cyclisation of readily prepared ester-aldimine substrates that will use an external nucleophilic source to promote catalytic turnover. This will solve the general problem of "external" catalytic turnover in Lewis base catalysis.
Please list any agreed training requirement
Calum will receive extensive training in catalysis and in particular enantioselective catalytic processes. This will cover synthesis and characterisation of new materials, as well as extensive mechanistic and kinetic analysis.
Background: We have previously shown that isothioureas promote a range of one-pot catalytic enantioselective cascade processes that rely upon the formation of a reactive ammonium enolate from readily available carboxylic acids. Although versatile, one drawback of this approach is that catalyst regeneration and turnover is promoted by intramolecular cyclisation (such as lactonisation). Building upon this work, this project will extend this process to the enantioselective cyclisation of readily prepared ester-aldimine substrates that will use an external nucleophilic source to promote catalytic turnover. This will solve the general problem of "external" catalytic turnover in Lewis base catalysis.
Please list any agreed training requirement
Calum will receive extensive training in catalysis and in particular enantioselective catalytic processes. This will cover synthesis and characterisation of new materials, as well as extensive mechanistic and kinetic analysis.
Organisations
Publications
McLaughlin C
(2019)
Base-free Enantioselective C(1)-Ammonium Enolate Catalysis Exploiting Aryloxides: A Synthetic and Mechanistic Study.
in Angewandte Chemie (International ed. in English)
Young CM
(2020)
The Importance of 1,5-Oxygen···Chalcogen Interactions in Enantioselective Isochalcogenourea Catalysis.
in Angewandte Chemie (International ed. in English)
McLaughlin C
(2021)
Generation and Reactivity of C(1)-Ammonium Enolates by Using Isothiourea Catalysis.
in Chemistry (Weinheim an der Bergstrasse, Germany)
Arokianathar JN
(2021)
Isothiourea-Catalyzed Enantioselective a-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides.
in Molecules (Basel, Switzerland)
McLaughlin C
(2021)
Catalytic enantioselective synthesis of 1,4-dihydropyridines via the addition of C(1)-ammonium enolates to pyridinium salts.
in Chemical science
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
EP/N509759/1 | 30/09/2016 | 29/09/2021 | |||
1792153 | Studentship | EP/N509759/1 | 30/09/2016 | 29/06/2020 | Calum McLaughlin |
Description | We have developed new reactivity with electrophiles in catalytic enantioselective reactions of esters using isothiourea catalysts. This employs an intermolecular catalyst turnover strategy, which was previously a challenge. We have carried out spectroscopic studies to detail the mechanism of these processes. |
Exploitation Route | New understanding of this chemistry will hopefully enable further new reactivity to be discovered. |
Sectors | Chemicals,Pharmaceuticals and Medical Biotechnology |