Catalytic Silylation of Aryl C-H Bonds with Earth Abundant Metal Catalysts

Lead Research Organisation: University of Nottingham
Department Name: Sch of Chemistry

Abstract

Silylation of organic molecules remains a potent challenge in the field of synthetic chemistry, still requiring lengthy synthetic pathways involving wasteful, intensive stages. Despite silyl-containing molecules having unique interactions with receptor proteins in the body, causing different pharmacochemical activities compared to a carbon analogue, this issue remains a fundamental roadblock in their application. In addition, catalysts for silylation reactions have historically been dominated by platinum-group metal-centred complexes such as those based on iridium and rhodium. These metals are significantly more expensive and also generally more toxic than their more earth abundant counterparts.

A number of other issues plague silylation chemistry currently. Hydrogen scavengers, such as alkenes are added to reaction mixtures in super stoichiometric quantities to drive the thermodynamic equilibrium of the reaction forwards. Directing groups are often needed for silylation reactions to progress and can be sensitive to the silane being used, the production of which uses wasteful, toxic reagents. Finally, to form the active catalytic species, stoichiometric or even super stoichiometric oxidants are needed to generate the active catalyst. As a result, the continued development of new catalysts and condition sets which combat these issues and allow access to different substrates is of paramount importance.
The aim will be to develop iron and manganese containing complexes with -accepting ligands and test their efficacy as homogeneous catalysts for the silylation of anisole as a standard to optimise the catalysts. Once the catalysts have been optimised for this aromatic, we will investigate functional group tolerance and selectivity, and will extend the methodology to different substrates, ranging from heteroaromatics (pyridine, pyrrole, furan, thiophene and indole) whilst also testing aromatics with weaker directing groups such as acetylbenzene with the aim of advancing eventually towards aromatics with weaker or no directing groups. From there, investigation on how the silane affects the reaction, such as whether is primary, secondary, or tertiary can be conducted. Throughout, kinetics and mechanistic studies will be conducted to elucidate mechanistic pathways of reaction. Based on these outcomes, calculations at a DFT level of theory may then be undertaken to compute activation barriers and provide further mechanistic insight.

Planned Impact

This CDT will deliver impact aligned to the following agendas:

People
A2P will provide over 60 PhD graduates with the skill sets required to deliver innovative sustainable products and processes into the UK chemicals manufacturing industry. A2P will inspire and develop leaders who will:
- understand the needs of industrial end-users;
- embed sustainability across a range of sectors; and
- catalyse the transition to a more productive and resilient UK economy.

Economy
A2P will promote a step change towards a circular economy that embraces resilience and efficiency in terms of atoms and energy. The benefits of adopting more sustainable design principles and smarter production are clear. For example, the global production of active pharmaceutical ingredients (APIs) has been estimated at 65,000-100,000 tonnes per annum. The scale of associated waste is > 10 million tonnes per annum with a disposal cost of more than £15 billion. Consequently, even a modest efficiency increase by applying new, more sustainable chemical processes would deliver substantial economic savings and environmental wins. A2P will seek and deliver systematic gains across all sectors of the chemicals manufacturing industry. Our goals of providing cross-scale training in chemical sciences with economic and life- cycle awareness will drive uptake of sustainable best practice in UK industry, leading to improved economic competitiveness.

Knowledge
This CDT will deliver significant new knowledge in the development of more sustainable processes and products. It will integrate the philosophy of sustainability with catalysis, synthetic methodology, process engineering, and scale-up. Critical concepts such as energy/resource efficiency, life cycle analysis, recycling, and sustainability metrics will become seamlessly joined to what is considered a 'normal' approach to new molecular products. This knowledge and experience will be shared through publications, conferences and other engagement activities. A2P partners will provide efficient routes to market ensuring the efficient translation and transferal of new technologies is realised, ensuring impact is achieved.

Society
The chemistry-using industries manufacture a rich portfolio of products that are critical in maintaining a high quality of life in the UK. A2P will provide highly trained people and new knowledge to develop smarter, better products, whilst increasing the efficiency and sustainability of chemicals manufacture.
To amplify the impacts of our CDT, effective public engagement and technology transfer will become crucially important. As a general comment, 'sustainability' styled research is often regarded in a positive light by society, however, the science that underpins its effective implementation is often poorly appreciated. The University of Nottingham has developed an effective communication portfolio (with dedicated outreach staff) to tackle this issue. In addition to more traditional routes of scientific communication and dissemination, A2P will develop a portfolio of engagement and outreach activities including blogs, webpages, public outreach events, and contribution of material to our award-winning YouTube channel, www.periodicvideos.com.

A2P will build on our successful Sustainable Chemicals and Processes Industry Forum (SCIF), which will provide entry to networks with a wide range of chemical science end-users (spanning multinationals through to speciality SMEs), policy makers and regulators. We will share new scientific developments and best practice with leaders in these areas, to help realise the full impact of our CDT. Annual showcase events will provide a forum where knowledge may be disseminated to partners, we will broaden these events to include participants from thematically linked CDTs from across the UK, we will build on our track record of delivering hi-impact inter-CDT events with complementary centres hosted by the Universities of Bath and Bristol.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S022236/1 30/09/2019 30/03/2028
2606329 Studentship EP/S022236/1 30/09/2021 29/09/2025 Lewis Munro