Enantioselective Amine alpha-C-H Functionalisation via Copper/Chiral Anion Cooperative Catalysis
Lead Research Organisation:
University of Strathclyde
Department Name: Pure and Applied Chemistry
Abstract
Many molecules possess a property that can be called 'handedness'. That is, they can exist in two forms that are non-superimposable mirror images of each other - like left and right hands. When a molecule has this property, it is said to be 'chiral' and the two mirror image forms are termed 'enantiomers'. Many important bioactive molecules possess this property and the number of such molecules is constantly increasing. One of the most significant implications of chiral drug molecules is that enantiomers can interact very differently with the body. For example, one enantiomer may elicit a beneficial therapeutic response while the other may be completely inactive or, in the worse case, cause life-threatening illnesses. As such, it is crucial that chemists are able to prepare chiral molecules in one pure enantiomeric form (whichever is desired), without contamination by the other.
'Amines' are a class of molecules that contain the element nitrogen and these, and their derivatives, represent some of the most commonly used and highly valued compounds within the chemical industry. Chiral amines, i.e. chiral compounds that display handedness at the nitrogen-bearing carbon atom, are molecules of exceptional importance within the chemical industry, and are present within many of the key molecular building blocks and final target compounds widely required within the pharmaceutical, agrochemical, and fine chemicals industries.
The continued development of bioactive agents (for example, pharmaceuticals and agrochemicals) and fine chemicals requires effective routes for the synthesis of chiral amines. Additionally, increasing environmental pressures dictate the requirement of "greener" strategies to replace out-dated and ineffective methods. The proposed research describes a novel approach to achieving this goal, ultimately leading to unprecedented access to these essential synthetic components using direct, catalytic, and clean technology based on a cooperative catalysis manifold.
'Amines' are a class of molecules that contain the element nitrogen and these, and their derivatives, represent some of the most commonly used and highly valued compounds within the chemical industry. Chiral amines, i.e. chiral compounds that display handedness at the nitrogen-bearing carbon atom, are molecules of exceptional importance within the chemical industry, and are present within many of the key molecular building blocks and final target compounds widely required within the pharmaceutical, agrochemical, and fine chemicals industries.
The continued development of bioactive agents (for example, pharmaceuticals and agrochemicals) and fine chemicals requires effective routes for the synthesis of chiral amines. Additionally, increasing environmental pressures dictate the requirement of "greener" strategies to replace out-dated and ineffective methods. The proposed research describes a novel approach to achieving this goal, ultimately leading to unprecedented access to these essential synthetic components using direct, catalytic, and clean technology based on a cooperative catalysis manifold.
Planned Impact
Academic Impact.
Scientific Advancement. This strategy targets the advancement of research within synthetic chemistry and is designed to complement and enhance the existing strategies within the high impact areas of C-H activation, copper catalysis, and chiral anion technology. Development of the described method will therefore be a timely and significant contribution within these expanding, internationally competitive domains, providing a series of new asymmetric methods and conceptual advances, whilst appreciably enhancing UK standing in both fields.
The programme will be broad in scope, generating a series of new and highly applicable reaction types that will facilitate the preparation of broadly desired molecular architectures. Successful realisation will impact upon research in a number of subject areas, providing (i) new approaches for asymmetric synthesis, (ii) new methods within organometallic chemistry, (iii) new avenues of research within physical-organic chemistry, and (iv) new approaches for sustainability-driven chemical synthesis. The interdisciplinary nature of the proposal is expected to result in expanded endeavours that will provide new avenues for research independent of the outlined programme and thereby provide a mechanism for wider, more general, and long term scientific impact.
Co-worker Training. The programme encompasses a wide range of techniques and will consequently provide the associated PDRA with broad scientific exposure. Additionally, as this work evolves, personnel exchange within both industry and academia will enable a parallel and wider training. Overall, this will afford the PDRA a diverse training and an advanced skill set and will provide UK industry or academia with a highly competent contributor.
Knowledge Exchange. As the programme develops, physical-organic chemistry will be extensively utilised to bring the reaction platform to fruition and interdisciplinary collaboration with colleagues engaged in these areas is anticipated to lead to new research horizons. Additionally, the exchange of co-workers with colleagues at other institutions will provide an additional method for interdepartmental and interdisciplinary knowledge exchange, the development of research alliances, and international scientific impact. Moreover, this programme is anticipated to be of specific interest to the chemical industry where strategic collaborations will be used to target applications and tailor future expansion of the methodology.
Economic and Societal Impact.
Industrial Application. This proposal specifically targets materials that are of increasing value in the chemical industry with the specific aim of fostering industrial impact and collaboration. The developed methods have also been designed to echo calls for synthetic sustainability, further facilitating adoption by industry. It is anticipated that this strategy will be of wide-ranging utility and will provide simple, elegant, and sustainable solutions to the production of important materials.
Business Potential. The expanding markets of the pharmaceutical, agrochemical, and fine chemical industries are continually prospecting for new enantioselective technologies to access chiral amines. In this regard, patentable processes and licensing agreements with industrial partners will be strongly pursued. This has the potential to set the foundations for establishing a spinout company that will employ the developed asymmetric processes to market a catalogue of chiral amine products to the industrial sector.
Societal Relevance. This new asymmetric method is expected to expedite the synthesis of important bioactive materials (drug entities, agrochemicals) and will therefore positively impact upon the standards of health in the UK and abroad. Additionally, the business-related outcomes of this research have the potential to generate employment opportunities within the UK and, consequently, impacting favourably upon the overall economy.
Scientific Advancement. This strategy targets the advancement of research within synthetic chemistry and is designed to complement and enhance the existing strategies within the high impact areas of C-H activation, copper catalysis, and chiral anion technology. Development of the described method will therefore be a timely and significant contribution within these expanding, internationally competitive domains, providing a series of new asymmetric methods and conceptual advances, whilst appreciably enhancing UK standing in both fields.
The programme will be broad in scope, generating a series of new and highly applicable reaction types that will facilitate the preparation of broadly desired molecular architectures. Successful realisation will impact upon research in a number of subject areas, providing (i) new approaches for asymmetric synthesis, (ii) new methods within organometallic chemistry, (iii) new avenues of research within physical-organic chemistry, and (iv) new approaches for sustainability-driven chemical synthesis. The interdisciplinary nature of the proposal is expected to result in expanded endeavours that will provide new avenues for research independent of the outlined programme and thereby provide a mechanism for wider, more general, and long term scientific impact.
Co-worker Training. The programme encompasses a wide range of techniques and will consequently provide the associated PDRA with broad scientific exposure. Additionally, as this work evolves, personnel exchange within both industry and academia will enable a parallel and wider training. Overall, this will afford the PDRA a diverse training and an advanced skill set and will provide UK industry or academia with a highly competent contributor.
Knowledge Exchange. As the programme develops, physical-organic chemistry will be extensively utilised to bring the reaction platform to fruition and interdisciplinary collaboration with colleagues engaged in these areas is anticipated to lead to new research horizons. Additionally, the exchange of co-workers with colleagues at other institutions will provide an additional method for interdepartmental and interdisciplinary knowledge exchange, the development of research alliances, and international scientific impact. Moreover, this programme is anticipated to be of specific interest to the chemical industry where strategic collaborations will be used to target applications and tailor future expansion of the methodology.
Economic and Societal Impact.
Industrial Application. This proposal specifically targets materials that are of increasing value in the chemical industry with the specific aim of fostering industrial impact and collaboration. The developed methods have also been designed to echo calls for synthetic sustainability, further facilitating adoption by industry. It is anticipated that this strategy will be of wide-ranging utility and will provide simple, elegant, and sustainable solutions to the production of important materials.
Business Potential. The expanding markets of the pharmaceutical, agrochemical, and fine chemical industries are continually prospecting for new enantioselective technologies to access chiral amines. In this regard, patentable processes and licensing agreements with industrial partners will be strongly pursued. This has the potential to set the foundations for establishing a spinout company that will employ the developed asymmetric processes to market a catalogue of chiral amine products to the industrial sector.
Societal Relevance. This new asymmetric method is expected to expedite the synthesis of important bioactive materials (drug entities, agrochemicals) and will therefore positively impact upon the standards of health in the UK and abroad. Additionally, the business-related outcomes of this research have the potential to generate employment opportunities within the UK and, consequently, impacting favourably upon the overall economy.
