Asymmetric Transfer Hydrogenation of Imines.
Lead Research Organisation:
University of Warwick
Department Name: Chemistry
Abstract
Many molecules have the potential to exist in one of two mirror image forms, known as 'enantiomers' (like your hands). Most significantly, a large proportion of the molecules from which biological organisms (cells, animals, plants, us) are made, including carbohydrates, protein and DNA, exist predominantly in a single enantiomeric form, i.e. as a single mirror image.This creates a challenging problem for the pharmaceutical, agrochemical and fine chemicals industries. If a new chemical is made, e.g. a potential drug, pesticide, intermediate etc., then this may also have to potential to exist as a mixture of enantiomers as well, depending on its structure. Although these molecules will be identical in many ways (as your hands are), they are likely to interact very differently with a biological system (i.e. if we swallow them), because they will be seen as two totally different compounds (try shaking hands with a friend's right hand and then with their left hand). The difference in biological effects, however, can be so great that now it is a legal requirement for chemical companies to make all new 'enantiomeric' compounds separately in each 'handedness' and to test each of these for safety and activity (sometimes only one enantiomer works as a drug, sometimes one is dangerous and one is beneficial). Furthermore, it is also often necessary for 'enantiomeric' compounds to be marketed in the single (i.e. most beneficial) handedness.The problem is that this (seemingly easy) task is in fact often quite difficult, because most of the most common and simple routes to new compounds form a 50:50 mixture of both 'enantiomers'. This is analogous to flipping a coin - as each molecule is made (each flip of the coin) then there is a 50:50 chance of making either handedness. To get a product of one 'handedness' it is necessary to make every single molecule the same way round (flip a head every time, or a tail every time). In our research at Warwick, we have developed a series of catalysts which generate 'enantiomeric' molecules through a single step process in which hydrogen is selectively added to a substrate to give a product in which one handedness significantly predominates over the other (i.e. it flips more heads than tails, or vice versa). As well as being active, and selective, the catalyst can be used at low loadings, typically below 0.5 % relative to substrate. This reduces waste, energy use and side products.In previous work, we have applied our catalysts to the synthesis of enantiomerically-pure (i.e. one handedness of) alcohols, which are a pivotal class of molecules represented in many pharmaceutical targets and intermediates. In this project, the catalysts will be adapted to be able to make a further pivotal class of molecules, amines, by adding hydrogen to a simple precursor molecule. If successful, this will provide an effective route to large numbers of valuable synthetic intermediates, target molecules, and complex products which would otherwise be very difficult to prepare.
People |
ORCID iD |
Martin Wills (Principal Investigator) |
Publications
G Nedden H
(2016)
The Development of Phosphine-Free "Tethered" Ruthenium(II) Catalysts for the Asymmetric Reduction of Ketones and Imines.
in Chemical record (New York, N.Y.)
Hopewell JP
(2012)
Developing asymmetric iron and ruthenium-based cyclone complexes; complex factors influence the asymmetric induction in the transfer hydrogenation of ketones.
in Organic & biomolecular chemistry
Martins J
(2009)
Asymmetric hydrogenation of ketones using Ir(III) complexes of N-alkyl-N'-tosyl-1,2-ethanediamine ligands
in Tetrahedron Letters
Martins J
(2010)
Applications of N'-alkylated derivatives of TsDPEN in the asymmetric transfer hydrogenation of CO and CN bonds
in Tetrahedron: Asymmetry
Martins JE
(2009)
Ru(II) complexes of N-alkylated TsDPEN ligands in asymmetric transfer hydrogenation of ketones and imines.
in Organic letters
Soni R
(2011)
The importance of the N-H bond in Ru/TsDPEN complexes for asymmetric transfer hydrogenation of ketones and imines.
in Organic & biomolecular chemistry
Wills M
(2016)
Imino Transfer Hydrogenation Reductions.
in Topics in current chemistry (Cham)
Description | AstraZeneca |
Amount | £22,000 (GBP) |
Funding ID | AstraZeneca contribution to DTA studentship |
Organisation | AstraZeneca |
Sector | Private |
Country | United Kingdom |
Start |
Description | AstraZeneca |
Amount | £22,000 (GBP) |
Funding ID | AstraZeneca contribution to DTA studentship |
Organisation | AstraZeneca |
Sector | Private |
Country | United Kingdom |
Start | 03/2009 |
End | 09/2013 |
Description | Asymmetric Catalysis Using Novel Iron Complexes |
Amount | £347,049 (GBP) |
Funding ID | EP/M006670/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 12/2014 |
End | 12/2017 |
Description | Commission of the European Communities |
Amount | £10,000 (GBP) |
Funding ID | STEPS EU funding for MSc student from Malta (C Zammit) |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start |
Description | Commission of the European Communities |
Amount | £10,000 (GBP) |
Funding ID | STEPS EU funding for MSc student from Malta (C Zammit) |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 10/2010 |
End | 09/2011 |
Description | EPSRC |
Amount | £60,000 (GBP) |
Funding ID | EPSRC project studentship in collaraboration with AstraZeneca |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2009 |
End | 09/2012 |
Description | EPSRC |
Amount | £136,826 (GBP) |
Funding ID | EP/G01244X/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start |
Description | EPSRC |
Amount | £32,000 (GBP) |
Funding ID | EP/H500308/1 Warwick Knowledge Transfer Secondments funding in Collaboration with Johnson Matthey. |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 10/2010 |
End | 12/2010 |
Description | EPSRC |
Amount | £32,000 (GBP) |
Funding ID | EP/H500308/1 Warwick Knowledge Transfer Secondments funding in Collaboration with Johnson Matthey. |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start |
Description | EPSRC |
Amount | £309,786 (GBP) |
Funding ID | EP/F042159/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start |
Description | EPSRC |
Amount | £309,786 (GBP) |
Funding ID | EP/F042159/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2009 |
End | 04/2012 |
Description | EPSRC |
Amount | £136,826 (GBP) |
Funding ID | EP/G01244X/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 10/2008 |
End | 03/2013 |
Description | EPSRC National Productivity Investment Fund DTP Studentship |
Amount | £5,000 (GBP) |
Organisation | AstraZeneca |
Sector | Private |
Country | United Kingdom |
Start | 10/2017 |
End | 09/2021 |
Description | WCPRS collaboration with Golden Keys 2017-2021 |
Amount | £45,000 (GBP) |
Organisation | The Golden Helix Foundation |
Sector | Private |
Country | United Kingdom |
Start | 10/2017 |
End | 09/2021 |
Description | Golden Keys Material Company collaboration |
Organisation | Golden Key, LLC |
Country | United States |
Sector | Private |
PI Contribution | Golden Keys Material Compnay LTd (China) co-funded a PHD student from October 2017-Sept 2021 to work on the development of asymmetric catalysis. |
Collaborator Contribution | Golden Keys will provide expertise and financial support to the project, with matched funding from Warwick University. |
Impact | No outputs yet. |
Start Year | 2017 |
Description | LEcture at Chiral India 29-30th October 2015, Mumbai, India |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A lecture on my research 29-30th October 2015, Mumbai, India |
Year(s) Of Engagement Activity | 2015 |