Bespoke Bimetallics for Chemical Cooperativity

Lead Research Organisation: University of Strathclyde
Department Name: Pure and Applied Chemistry

Abstract

The importance of the UK's chemical and pharmaceutical sector can be seen in the statistic that it supplies £60M of added value each working day (that equates to £15bn a year) to our Gross Domestic Product (the total value of goods and services provided by a country in one year).

Cutting edge research, innovation and sustainability lie at the heart of this project. The research is in organometallic chemistry, a core area of chemistry that is utilised in a myriad of real world applications, spanning chemistry and other disciplines such as biochemistry and material science. Organometallic compounds, comprising an organic moiety and a metal moiety are essential tools for constructing molecules big and small. A large proportion of known chemical processes depend on the metal moiety of organometallic compounds being a precious transition metal (commonly palladium, platinum, rhodium, iridium, ruthenium, and osmium), which are essential for the manufacture of numerous specialty chemicals from agrochemicals through to pharmaceuticals (especially anticancer drugs).

Base (non-precious) metals are generally much cheaper (due to their higher natural abundance) and reflecting this high abundance in the earth's crust they have less toxicity concerns than their precious metal counterparts. The problem is their chemistry (their ability to carry out useful reactions efficiently) is rather limited by comparison so more often than not they are inefficient in many chemical processes. If base metal chemistry could be developed to the status of precious transition metal chemistry or better still to go beyond this status, then sustainability would be significantly improved and reliance on less environmentally benign precious transition metals would be reduced.

Recent advances by the research team have demonstrated that base chemistry can be made orders of magnitude more efficient by preparing organometallic compounds that contain two base metal elements instead of one. The metal common to all of these metal pairs is an alkali metal (lithium, sodium or potassium), while the second metal is magnesium, zinc, aluminium or the earth-abundant transition metals iron and manganese. By forming mixed-metal bimetallic structures impossible in single-metal systems, cooperative effects are induced which transform the reactivity of the base metals opening up a vast number of novel reactions that are currently inaccessible to base metals on their own. Cooperativity will be especially important in our targeted C-C bond formations and C-F bond activations through alkali metal -Fe or -Mn partnerships as currently these reactions are generally the domain of precious transition metal catalysis.

Realising this escalation of sustainable base metal chemistry will be a major breakthrough in itself but this project will take on an additional ambitious challenge. Alkali metal organometallic chemistry invariably needs to be performed under anaerobic conditions as the compounds involved rapidly decompose with even traces of air or moisture. However, the team recently made the extraordinary finding that certain organoalkali metal reactions could be run under aerobic conditions by using Deep Eutectic Solvents (DES) as opposed to industry standard classical organic solvents. DES are more cost-effective, greener and biorenewable than organic solvents and switching to them would also do away with the need for costly inert atmosphere protocols. The proof of concept results with DES have been with single base metals, so the challenge is to develop this new bimetallic chemistry in DES. Success will impact the practice of organometallic chemistry worldwide.

Planned Impact

There is huge potential scope for widespread impact of cooperative bimetallic chemistry in manufacturing underpinning technological developments over several sectors and thus contributing to a more productive UK economy.

Advancing the bimetallic chemistry of earth-abundant elements will ensure sustainability of numerous ongoing and yet to be discovered chemical processes to mitigate overexploitation and environmental concerns of precious transition metals. The cooperativities induced by bimetallic pairings promise not just emulation of precious transition metal chemistry that exceeds the limits of single-metallic systems; but also new chemistry unknown even with precious transition metals.

Developing innovative atom-economical, greener solvent, mild temperature earth abundant mixed-metal synthetic methodologies for functionalising organic molecules with "incompatible" groups will have economic benefits in the scale up of industrial processes. The impact of new technologies, based mainly on environmentally-friendly solvents such as DESs, would be of substantial long term benefit to large multinational industries (e.g. pharmaceutical, agrochemical, organic materials, and cosmetic). Many advantages would be realised including greater sustainability, safer working practices, and large cost savings as well as minimising use or generation of toxic chemicals. Every UK household could potentially benefit as numerous commodity chemicals (pharmaceuticals, cosmetics, dyes, polymers, etc.) need polar organometallic methodologies in their preparation. Accessing pharmaceuticals at lower prices is a priority public policy issue. Continued pharmaceutical innovation is also essential for increases in longevity, a better health, higher productivity and economic growth. Note that one common salt used for synthesising DESs is choline chloride, which is produced on a scale of million metric tons per year (ca. 2 £/Kg) and it is not only cheap and extractable from biomass but also non-toxic and biodegradable. Collectively, fundamental understanding and bimetallic technologies generated during this project will allow for rapid exploitation and commercialisation of mixed-metal reagents. The impact of this work will be felt in various areas, most directly those dealing with fine chemicals manufacturing, minimising its environmental impact.

As processes using cooperative bimetallics and DES are implemented by industry, fine chemical and pharmaceutical manufacturing will change, incorporating these more economical and sustainable methodologies, that will have a positive impact on wealth and environment. Our industrial partner Janssen has immediately seen the potential benefits of this work. Janssen will provide industry pull advice and assistance to this project. To ensure this research is widely disseminated a twitter account highlighting our own and competitor developments in bimetallic chemistry and DES applications in polar organometallic chemistry will be created. A 'Power Symposium" is also planned in year 2 on the applications of cooperative bimetallics, highlighting challenges within the development of transition-metal free bond forming protocols and the use of novel solvent systems, connecting with both industrial stakeholders and expert researchers in organometallic chemistry.

This project will also provide training/networking opportunities for both PDRAs, enabling them to launch their careers in this exciting, rapidly growing field. Their development will be broadened by interactions with the European academics and industrialists involved in the project, with the latter giving them valuable insight into the industrial context of their research. The UK will therefore benefit from trained researchers and potentially licensable new technologies using cooperative bimetallics and DES. A variety of public engagement activities and media coverage will be pursued to ensure the wider public recognizes the implications of this project.

Publications

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Banerjee S (2023) Three Oxidative Addition Routes of Alkali Metal Aluminyls to Dihydridoaluminates and Reactivity with CO2. in Chemistry (Weinheim an der Bergstrasse, Germany)

 
Description Having been kept out of our research laboratory for several months due to restrictions caused by covid, my research associate Dr Thomas Gentner and I carried out a comprehensive literature review that produced a new concept which we have called "alkali metal mediation". This concept has since been published in both the English and German versions of the international journal Angewandte Chemie. The concept relates to organometallic compounds, a core class of reagent that is vital to synthesis and catalysis. This concept reveals that alkali metal organometallic compounds can mediate the chemistry of other compounds in applications including main group homogeneous catalysis, stoichiometric organic synthesis, low valent main group metal chemistry, polymerization and green chemistry. Thus, this review has been written to alert the chemistry community to the power of this rising unifying phenomenon of "alkali metal mediation".

In the laboratory we extended this concept experimentally by designing new alkali metal catalysts for transfer hydrogenation catalysis. In keeping with the title of the project, we have developed cooperative bimetallic systems starting with magnesium. Homogeneous hydrogenation is a synthetic procedure of fundamental importance to the chemical industry as well as being one of the most extensively studied reactions in homogeneous catalysis so following their preparation and characterisation we tested our new lithium-magnesium and sodium-magnesium systems for the transformation of alkenes to alkanes using 1,4-cyclohexadiene as the hydrogen source, but the results were poor. However, on screening all of the alkali metals including the heavier alkali metals, potassium, rubidium and caesium, pleasingly we found that these new alkali metal magnesium systems were efficient catalysts, though the best catalyst was dependent on the nature of the alkene. This advance opened up a new line of research in the project, expanding the experimental programme to all of the non-radioactive alkali metals (Li, Na, K, Rb, Cs) not just Li, Na and K.

In the final year of the project we exploited this "alkali metal mediation" to the earth-abundant, non-toxic transition metal manganese and main group metal aluminium the most abundant metal in the earth's crust. The choice of this transition metal is important as most catalytically active transition metals such as Pt, Pd, Rh, and Ir are precious, expensive and harmful to the environment, so replacing them with a more economical, abundant, environmentally friendly metal would be beneficial especially in the quest for long term sustainability of chemical processes requiring metal catalysts. Towards this aim, here we prepared and crystallographically characterised several Rb and Cs manganate complexes. These proved challenging to prepare but we established that the key to their preparation was avoiding certain solvents (Lewis base donor types). Their crystal structures provided a lot of useful information on which interactions hold these mixed-metal structures together, and such information will be useful to guide the mechanistic processes taking place when utilising these complexes in future catalytic processes. With regard to aluminium, we prepared a series of alkali metal aluminates containing a "surrogate hydride". Hydrides are very important in synthesis, but many alkali metal hydrides are insoluble. But our surrogate hydrides are soluble in organic solvents and actually have very polar C-H bonds, which can release hydrides, hence the surrogacy label, simply upon gentle heating.

With these alkali metal manganate and mixed-metal aluminium compounds now in hand, the way ahead is clear to investigate the application of these complexes in stoichiometric and catalytic reactions, that will be of interest both academically and industrially.
Exploitation Route As the breakthrough with the heavier alkali metals Rb and Cs has been published in ChemCatChem together with our perspective article in Angewandte Chemie these findings should stimulate widespread academic interest. Tangible evidence for this interest is provided by the fact the latter published as recently as 2021 has already received 78 citations (scopus 28/02/23).
Currently, the chemistry community is devoting more attention to elements that are more sustainable in alignment with the "United Nations Sustainable Developments Goals". The advances made in the project with alkali metals, aluminium, and manganese can inspire more chemists to use these elements and related elements in synthesis and catalysis as alternatives to precious transition metals which may suffer from supply problems due to their low abundance and geopolitical events. Reflecting this interest, I was recently invited to join a European Collaboration involving ten countries (Austria, Belgium, France, Germany, Poland, Slovenia, Spain, Sweden, Switzerland, and the UK) as part of a now submitted application for an EC Horizon MSCA Doctoral Network Award on "Cooperative Bimetallics for Catalysis and Materials".
Sectors Chemicals

Education

Pharmaceuticals and Medical Biotechnology

 
Description It is still early days regarding potential non-academic impact. Our first experimental breakthrough was reported in ChemCatChem (2021, 13, 2371; 28 citations, FWCI, 2.78), where we screened all Group 1 metals (Li-Cs), in combination with magnesium in catalytic transfer hydrogenation of alkenes, finding that caesium produced the largest cooperative influence. This fact, the most surprising and significant of the whole project, opened up a new potentially rich furrow of investigation for the project as the initial plan was to focus on the lighter alkali metals Li, Na and K, but with this spectacular result Rb and Cs had to be included. Potential was then realised in practice with the Hot Paper in Angewandte Chemie (2023, 62, e202304966) "Alkali Metal Dihydropyridines in Transfer Hydrogenation Catalysis of Imines: Amide Basicity versus Hydride Surrogacy", where again the catalytic capacity of Cs proved higher than that of all the other alkali metals. Going forward the work now is aiming to develop organocaesium chemistry and bring it into the mainstream of organometallic chemistry for fine chemical manufacture and catalysis. Two grants have been awarded recently to attempt to realise this aim. One from the Leverhulme Trust (RPG-2023-248: £305K, beginning on April 2024) the other award from Innospec Ltd, Ellesmere Port contributing £45K towards a PhD studentship.
First Year Of Impact 2023
 
Description Propelling Sodium to the Forefront of Metallation Chemistry
Amount £250,408 (GBP)
Funding ID RPG-2019-264 
Organisation The Leverhulme Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2020 
End 03/2024
 
Description Rational Development of Organocaesium Chemistry
Amount £305,056 (GBP)
Funding ID RPG-2023-248 
Organisation The Leverhulme Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2024 
End 03/2028
 
Title Alkali Metal (Li, Na, K, Rb, Cs) Mediation in Magnesium Hexamethyldisilazide [Mg(HMDS)2] Catalysed Transfer Hydrogenation of Alkenes 
Description This study reports successful catalytic transfer hydrogenation of alkenes with the s-block compound, magnesium bis-hexamethyldisilazide when combined with alkali metals in heterobimetallic complexes. By screening the complete Group 1 series of metals (Li-Cs), the efficiency of these catalyses gives an indication of the relative power of the synergistic effect exerted on magnesium by the alkali metal. In the absence of the alkali metal the magnesium amide is ineffective as a catalyst. The dataset contains two files; namely NMR data (zip file) and X-ray crystallographic information file (zip file). 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact None so far. 
 
Title Data for: "Rubidium and caesium aluminyls: synthesis, structures, and reactivity in C-H bond activation of benzene" 
Description This work is associated with the epsrc project "Bespoke Bimetallics for Chemical Cooperativity" (award number EP/S029788/1). The data is provided in 5 separate files. These cover NMR raw data, synthetic procedures, X-ray raw data for the rubidium structure; X-ray raw data for the caesium structure, and a combined CIF for both structures. Note that specialist programs are required to view the raw data provided: the NMR data in requires a program such as Topspin or Mestrelab to view. The X-ray crystallographic information requires a program such as Mercury or Diamond. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact Too early as just recently released 
URL https://pureportal.strath.ac.uk/en/datasets/e59234ad-9d5b-4fcd-8254-434f0870db11
 
Title Heavier Alkali Metal Manganate Complexes: Synthesis, Structures and Solvent-Induced Dissociation Effects 
Description The dataset contains the following four files: 1) Elemental analysis data files (EA_GBallmann) 2) NMR data files (NMR_GBallmann) 3) Infrared data files (IR_GBallmann) 4) X-Ray data files (XRD_GBallmann) The dataset relates to the research reported in the manuscript in the title, carried out as part of the EPRSC funded project. Please note that the NMR data requires a specialised programme such as Topspin or MestreLab, and the XRD data (.cif) requires a programme such as OLEX2 or Mercury to view, and the IR requires a programme such as Origin or Excel to view. Note the paper is published in Chemistry a European Journal. 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
Impact The data in this paper provided the primary findings in the published paper in Chemistry a European Journal 2022, 28, e202201716 
URL https://pureportal.strath.ac.uk/en/datasets/7fc4c5a1-535a-4204-bee8-58821f91b22d
 
Title Products from Oxidative Addition of Phenylsilane to the Complete Series of [AM{Al(NONDipp)}]2 Aluminyl Complexes (AM = Li, Na, K, Rb, Cs) 
Description The dataset contains the following 3 files: 1. IR Data (zip file) 2. NMR Data (zip file) 3. X-Ray raw data (zip file) The dataset relates to research reported in the manuscript in the title, carried out as part of the EPSRC funded (EP/S029788/1) project in collaboration with Prof. Martyn Coles group in Victoria University of Wellington, New Zealand (Funding for the Martyn Coles group: Government funding from the Marsden Fund Council, managed by Royal Society Te Aparangi; Grant Number: MFP-VUW2020). Please note that the NMR data requires a specialist program such as Topspin or Mestrelab, and the X-Ray data (.cif) requires a program such as Olex or Mercury to view. The IR data can be viewed using Origin software. 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
Impact The results obtained in this dataset were presented in the American Chemical Society journal "Inorganic Chemistry" 2022, 61, 19838-19846. 
URL https://pureportal.strath.ac.uk/en/datasets/477fd1d6-12b7-441b-a1d1-931f08ce47b8
 
Description Martyn Coles Group Victoria University of Wellington, New Zealand 
Organisation Victoria University of Wellington
Country New Zealand 
Sector Academic/University 
PI Contribution Having met at an online international conference, Royal Society of Chemistry Dalton 2020, we initiated this new collaboration in 2020. The New Zealand group send us highly specialised, low valent aluminium compounds, which we then use to make bimetallic alkali metal aluminium compounds through our complementary expertise. We then characterise these compounds by X-ray crystallography and NMR spectroscopic studies, and screen them in a series of key catalytic reactions involving important organic transformations.
Collaborator Contribution The New Zealand group prepare challenging to make precursor low valent aluminium compounds for our collaborative research programme. They send them to the UK via special delivery postal services together with full characterisation data so we can check their purity following the long journey. We support this collaboration by joint research group meetings every month. We both contributed to the writing of the research paper.
Impact Publication: T. X. Gentner, M. J. Evans, A. R. Kennedy, S. E. Neale, C. L. McMullin, M. P. Coles and R. E. Mulvey, Rubidium and caesium aluminyls: synthesis, structures and reactivity in C-H bond activation of benzene, Chemical Communications 2022, 58, 1390. This collaboration is not multi-disciplinary.
Start Year 2020
 
Description An oral presentation at the 29th International Conference on Organometallic Chemistry (ICOMC 2022), Prague, Czech Republic. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Conference oral presentation by my research associate Dr G. Ballmann entitled "Synthesis, structure and reactivity of rubidium and caesium aluminium hydrides made from their parent aluminyls". Stimulated much discussion both after the lecture and at various times during the conference. Helped Dr Ballmann in planning his future career steps.
Year(s) Of Engagement Activity 2022
URL https://www.icomc2022.cz
 
Description Invited Lecture (Institute of Inorganic Chemistry; University of Stuttgart, Germany; virtual) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Was a seminar given to the inorganic section of the university comprising academic staff, postdoctoral research associates and postgraduate students. Established a new collaboration with another group on the basis of this lecture. Will include a student exchange in due course.
Year(s) Of Engagement Activity 2020
 
Description Invited Lecture (Ruhr-Universität Bochum, Germany; Virtual) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Was a summer school on solvation science given virtually on zoom as part of the RESOLV, cluster of excellence programme in Germany. Approaching 100 postgraduates from all different areas of science attended, together with a few other academics. Talk was more of a general nature, introducing the audience to the importance of science in organic alkali metal chemistry. Had a lively discussion afterwards on the potential of the research for future exploitation in different areas.
Year(s) Of Engagement Activity 2021
 
Description Invited Oral Presentation at the ACS Spring Meeting, Indianapolis, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited presentation at the American Chemical Society Spring Meeting, Indianapolis, USA, Abstract 3817019 INOR. Part of the Harry Gray Award for Creative Work in Inorganic Chemistry by a Young Investigator: Symposium in Honour of Robert J. Gilliard, Jr.
Year(s) Of Engagement Activity 2023
URL https://acs.digitellinc.com/sessions/531154/view
 
Description Invited Oral Presentation at the XXXIX Reunión Bienal De La Real Sociedad Espanola De Quimica (RSEQ), Zaragoza, Spain. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited presentation which attracted lots of interest during and afterwards, the latter through discussions with several other delegates from Spain, Italy and Switzerland.
Year(s) Of Engagement Activity 2023
URL https://rseq.org/xxxix-reunion-bienal-de-la-rseq/
 
Description Keynote Lecture: R. E. Mulvey. 29th International Conference on Organometallic Chemistry (ICOMC 2022), Prague, Czech Republic, 2022 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented a keynote lecture at this five day international conference entitled "Putting on weight: Heavy alkali metal mediation in synthesis and catalysis". First live conference I attended since the pandemic lockdowns. Excellent forum for discussing chemistry and making new connections. Helped me make contacts that led to me joining a European Doctoral Network.
Year(s) Of Engagement Activity 2022
URL https://www.icomc2022.cz
 
Description Oral presentation at the ACS Fall Meeting, Chicago, USA. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented a lecture entitled "Beyond lithium: developing the chemistry of heavy alkali metal amides", at the American Chemical Society National Meeting in Chicago, USA. Conference presented an excellent networking opportunity. Subsequently was invited to a special award symposium for the ACS National Meeting in Indianapolis in 2023.
Year(s) Of Engagement Activity 2022
URL https://www.acs.org/meetings/acs-meetings.html?sc=220414_mtg_em_FALL22_cds_od
 
Description Plenary Lecture organised by RSC-IISER (Indian Institute for Science and Education Research). A virtual event. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Plenary lecture at a virtual conference RSC-IISER (Indian Institute for Science and Education Research) Desktop Seminar, Thiruvananthapuram, India (virtual presentation), 2022. Nearly one thousand delegates in attendance.
Helped me establish promising contacts with the Inorganic Chemistry community in India. Received an invitation to visit Universities in India as a result.
Year(s) Of Engagement Activity 2022
URL https://www.rsc.org/events/detail/73614/rsc-iiser-desktop-seminar-with-dalton-transactions
 
Description Visit of research collaborator from Oviedo University in Spain. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Invited Associate Professor J. Garcia-Alvarez, a project partner on the grant award, for a week at my university to discuss future collaboration plans. Previous intended visits from Glasgow to Oviedo and vice versa were cancelled due to the pandemic.
Year(s) Of Engagement Activity 2022