First-row Transition Metal Catalysed Synthesis of Organophosphorus Compounds
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Chemistry
Abstract
Organophosphorus compounds are of considerable importance due to their many applications as medicines, agrochemicals, fire retardants and ligands.1 Classical synthetic methodologies to synthesise these compounds using heat, light or radical initiators suffer significantly from the use of stoichiometric additives, the use of protecting groups, poor functional group tolerance and the formation of regiochemical mixtures of organophosphorus products.2 The need for a less wasteful and more regioselective and stereoselective method of organophosphorus synthesis has promoted the use of metal catalysts to form P-C bonds; by addition of a P-H unit to an unsaturated carbon-carbon double bond.3 This methodology is ideal because it presents the potential to be a 100% atom economic process, in line with one of 12 Principles of Green Chemistry.4 However, a significant proportion of the metal catalysts commonly used in these reactions are precious metal catalysts, mainly palladium and to a lesser extent early lanthanides.2 Additionally, the majority of recent literature has focused on P-H addition using secondary phosphines to unfunctionalised alkenes and alkynes, due to a lack of suitable catalysts that can tolerate heteroatom functionality. This is problematic as the secondary phosphines used are originally derived from PCl3, which is classified as very toxic and corrosive under EU Directive 67/548/EEC. To circumvent these issues, more environmentally benign phosphorus precursors and earth-abundant robust transition metal catalysts are needed to make this methodology more sustainable.
Previous research by the Kays group has shown that low co-ordinate iron complexes can catalyse P-H addition to heteroatom-functionalised substrates such as isocyanates (R-N=C=O). Significantly these complexes have also been shown to catalyse novel diinsertion pathways for this reaction, which are exceedingly rare and typically difficult to control (e.g. Scheme 1). Building on this work the project will utilise low coordinate first-row transition metal complexes to catalyse the addition of a range of P-H and P(O)-H derivatives to heterocumulenes containing C=X (X = O, N, S) bonds, to introduce a heteroatom functionality efficiently into organophosphorus compounds with novel motifs relevant to pharmaceutical and agrochemical industries. A key part of the project will be to use more sustainable and benign organophosphorus derivatives which can present more challenge to the catalysis as a much broader pKa range and more functional groups compared will be used compared to typical hydrophosphination reactions. Expansion of the reactivity to other additions will allow us to explore the applicability of the first-row transition metal precatalysts. Reaction mechanisms will be investigated using detailed kinetic experiments and will help inform future reaction development at the gram scale with green solvents.
Previous research by the Kays group has shown that low co-ordinate iron complexes can catalyse P-H addition to heteroatom-functionalised substrates such as isocyanates (R-N=C=O). Significantly these complexes have also been shown to catalyse novel diinsertion pathways for this reaction, which are exceedingly rare and typically difficult to control (e.g. Scheme 1). Building on this work the project will utilise low coordinate first-row transition metal complexes to catalyse the addition of a range of P-H and P(O)-H derivatives to heterocumulenes containing C=X (X = O, N, S) bonds, to introduce a heteroatom functionality efficiently into organophosphorus compounds with novel motifs relevant to pharmaceutical and agrochemical industries. A key part of the project will be to use more sustainable and benign organophosphorus derivatives which can present more challenge to the catalysis as a much broader pKa range and more functional groups compared will be used compared to typical hydrophosphination reactions. Expansion of the reactivity to other additions will allow us to explore the applicability of the first-row transition metal precatalysts. Reaction mechanisms will be investigated using detailed kinetic experiments and will help inform future reaction development at the gram scale with green solvents.
Planned Impact
This CDT will have a positive impact in the following areas:
PEOPLE. The primary focus is people and training. Industry needs new approaches to reach their sustainability targets and this is driving an increasing demand for highly qualified PhD graduates to lead innovation and manage change in the area of chemicals production. CDT based cohort training will provide industry ready scientists with the required technical competencies and drive to ensure that the sector retains its lead position in both innovation and productivity. In partnership with leading chemical producers and users, we will provide world class training to satisfy the changing needs of tomorrow's chemistry-using sector. Through integrated links to our Business School we will maximise impact by delivering dynamic PhD graduates who are business aware.
ECONOMY. Sustainability is the major issue facing the global chemical industry. Not only is there concern for our environment, there is also is a strong economic driver. Shareholders place emphasis on the Dow Jones Sustainability Index that tracks the performances of the sector and engenders competition. As a result, major companies have set ambitious targets to lower their carbon footprints, or even become carbon neutral. GSK CEO Sir Andrew Witty states that "we have a goal to reduce our emissions and energy use by 45% compared with 2006 levels on a per unit sales basis... " Our CDT will help companies meet these challenges by producing the new chemistries, processes and people that are the key to making the step changes needed.
SOCIETY. The diverse range of products manufactured by the chemical-using industries is vital to maintain a high quality of life in the UK. Our CDT will have a direct impact by ensuring a supply of people and new knowledge to secure sustainability for the benefit of all. The role of chemistry is often hidden from the public view and our CDT will provide a platform to show chemical sciences in a positive light, and to demonstrate the importance of engineering and applications across biosciences and food science.
The "green and sustainable" agenda is now firmly fixed in the public consciousness, our CDT will be an exemplar of how scientists and engineers are providing solutions to very challenging scientific and technical problems, in an environmentally benign manner, for the benefit of society. We will seek sustainable solutions to a wide range of problems, whilst working in sustainable and energy efficient facilities. This environment will engender a sustainability ethos unique to the UK. The CNL will not only serve as a base for the CDT but also as a hub for science communication.
Public engagement is a crucial component of CDT activities; we will invite input and discussion from the public via lectures, showcases and exhibition days. The CNL will form a hub for University open days and will serve as a soft interface to give school children and young adults the opportunity to view science from the inside. Through Dr Sam Tang, public awareness scientist, we have significant expertise in delivering outreach across the social spectrum, and she will lead our activities and ensure that the CDT cohorts engage to realise the impact of science on society. Martyn Poliakoff, in his role as Royal Society Foreign Secretary, will ensure that our CDT dovetails with UK science policy.
KNOWLEDGE. In addition to increasing the supply of highly trained people, the results of the PhD research performed in our CDT will have a major impact on knowledge. Our student cohorts will tackle "the big problems" in sustainable chemistry, and via our industrial partners we will ensure this knowledge is applied in industry, and publicised through high level academic outputs. Our knowledge-based activities will drive innovation and economic activity, realising impact through creation of new jobs and securing the future.
PEOPLE. The primary focus is people and training. Industry needs new approaches to reach their sustainability targets and this is driving an increasing demand for highly qualified PhD graduates to lead innovation and manage change in the area of chemicals production. CDT based cohort training will provide industry ready scientists with the required technical competencies and drive to ensure that the sector retains its lead position in both innovation and productivity. In partnership with leading chemical producers and users, we will provide world class training to satisfy the changing needs of tomorrow's chemistry-using sector. Through integrated links to our Business School we will maximise impact by delivering dynamic PhD graduates who are business aware.
ECONOMY. Sustainability is the major issue facing the global chemical industry. Not only is there concern for our environment, there is also is a strong economic driver. Shareholders place emphasis on the Dow Jones Sustainability Index that tracks the performances of the sector and engenders competition. As a result, major companies have set ambitious targets to lower their carbon footprints, or even become carbon neutral. GSK CEO Sir Andrew Witty states that "we have a goal to reduce our emissions and energy use by 45% compared with 2006 levels on a per unit sales basis... " Our CDT will help companies meet these challenges by producing the new chemistries, processes and people that are the key to making the step changes needed.
SOCIETY. The diverse range of products manufactured by the chemical-using industries is vital to maintain a high quality of life in the UK. Our CDT will have a direct impact by ensuring a supply of people and new knowledge to secure sustainability for the benefit of all. The role of chemistry is often hidden from the public view and our CDT will provide a platform to show chemical sciences in a positive light, and to demonstrate the importance of engineering and applications across biosciences and food science.
The "green and sustainable" agenda is now firmly fixed in the public consciousness, our CDT will be an exemplar of how scientists and engineers are providing solutions to very challenging scientific and technical problems, in an environmentally benign manner, for the benefit of society. We will seek sustainable solutions to a wide range of problems, whilst working in sustainable and energy efficient facilities. This environment will engender a sustainability ethos unique to the UK. The CNL will not only serve as a base for the CDT but also as a hub for science communication.
Public engagement is a crucial component of CDT activities; we will invite input and discussion from the public via lectures, showcases and exhibition days. The CNL will form a hub for University open days and will serve as a soft interface to give school children and young adults the opportunity to view science from the inside. Through Dr Sam Tang, public awareness scientist, we have significant expertise in delivering outreach across the social spectrum, and she will lead our activities and ensure that the CDT cohorts engage to realise the impact of science on society. Martyn Poliakoff, in his role as Royal Society Foreign Secretary, will ensure that our CDT dovetails with UK science policy.
KNOWLEDGE. In addition to increasing the supply of highly trained people, the results of the PhD research performed in our CDT will have a major impact on knowledge. Our student cohorts will tackle "the big problems" in sustainable chemistry, and via our industrial partners we will ensure this knowledge is applied in industry, and publicised through high level academic outputs. Our knowledge-based activities will drive innovation and economic activity, realising impact through creation of new jobs and securing the future.
