Hydrogenation of ketones without transition metal catalysts.
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). However a drawback of the catalysts that we have so far developed is that they are based on relatively toxic transition metals, all traces of which must be carefully removed from the products if they are to be used as a drug or for human or animal use.The objective of this project is to develop new catalysts for the enantiomeric reactions (i.e. hand selective) reactions described above which contain more benign metals in place of the transition metals. These might be, for example, sodium, potassium or iron based, although a wide range of metals shall be tested. There is literature precedent for the work in this proposal, which indicates that the process is viable at high temperatures and pressures using potassium as the central metal. In this project we would aim to prepare new ligands which are active at much lower temperatures and pressures, in order to make the process more versatile.As well as modifying the catalyst so that the high reaction rates and highest selectivity (for one 'handedness' of product) can be obtained, a broad range of products will be prepared. The proposed target compounds represent a wide range of physiologically-important targets and include several compounds which have useful biological properties. The selected ketones represent a range of diverse substrates (hence ensuring the maximum benefit from the project) and include a number of particularly challenging molecules for which no satisfactory methods currently exist.
People |
ORCID iD |
Martin Wills (Principal Investigator) |
Publications
Jolley K
(2015)
Tethered Ru(II) catalysts containing a Ru-I bond
in Journal of Organometallic Chemistry
Jolley K
(2012)
Application of Tethered Ruthenium Catalysts to Asymmetric Hydrogenation of Ketones, and the Selective Hydrogenation of Aldehydes
in Advanced Synthesis & Catalysis
Jolley Katherine E.
(2013)
Development of catalysts for asymmetric hydrogenation
Soni R
(2013)
Direct formation of tethered Ru(II) catalysts using arene exchange.
in Organic letters
Description | We developed a number of new catalysts for a range of challenging chemical conversions. We also developed a novel and much improved method for their preparation. |
Exploitation Route | Our novel catalysts can be used by researchers in academic and industrial groups in a range of applications. In particular for chemicals and fine synthesis research. |
Sectors | Chemicals,Pharmaceuticals and Medical Biotechnology |
URL | http://www2.warwick.ac.uk/fac/sci/chemistry/research/wills/willsgroup/publications/ |
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 | Development of the future generation of catalysts for asymmetric reduction |
Amount | £107,911 (GBP) |
Funding ID | 101330 |
Organisation | Innovate UK |
Sector | Public |
Country | United Kingdom |
Start | 05/2013 |
End | 06/2014 |
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 | Oxidation reactions assisted by energy from sunlight |
Amount | £173,000 (GBP) |
Funding ID | RPG-374 |
Organisation | The Leverhulme Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 04/2012 |
End | 06/2015 |
Description | Oxidation reactions assisted by energy from sunlight |
Amount | £173,000 (GBP) |
Funding ID | RPG-374 |
Organisation | The Leverhulme Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2012 |
End | 06/2015 |
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 |
Title | CATALYST AND PROCESS FOR SYNTHESISING THE SAME |
Description | The invention relates to a method for synthesising tethered ruthenium catalysts and novel tethered ruthenium catalysts obtainable by this methods. The method involves carrying out an "arene swapping" reaction avoiding the requirement to use complicated techniques making use of unreliable Birch reductions and unstable cyclodienyl intermediates. |
IP Reference | WO2014068331 |
Protection | Patent application published |
Year Protection Granted | 2014 |
Licensed | No |
Impact | The work in the patent contributed to an Impact Case Study for the REF in 2014. |
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 |
Description | Participation in EUCHEMS conference Liverpool 26-30 August 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation of talk and poster at the August 2018 EUCHEMS conference at Liverpool 26-30th August 2018. |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.euchems2018.org/ |
Description | Participation in a workshop in Guiyang, China, March 2018 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I helped to organize and spoke at a symposium organized by Golden Keys High Tech material Company, Guiyang, China, March 21st 2018. |
Year(s) Of Engagement Activity | 2018 |
Description | Submitted lecture at Dalton Conference 2018 at Warwick University April 3-5th 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Submitted lecture at Dalton Conference 2018 at Warwick University April 3-5th 2018 |
Year(s) Of Engagement Activity | 2018 |
URL | http://www.rsc.org/events/detail/27854/dalton-2018 |