Catalytic Stereoretentive-Enantioconvergent Cross-Coupling Reactions

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

Abstract

This project will experimentally establish a new concept in asymmetric synthesis: stereoretentive-enantioconvergent
catalysis. This will represent a completely new method for accessing enantiopure materials starting from racemic
substrates and will therefore impact all areas of synthetic chemistry. The ability to synthesise chiral molecules in
enantiopure form is vitally important, most recognisably for the pharmaceutical industry. This is because the molecules of
life are chiral (e.g., D-sugars and L-amino acids) and enantiomers often interact very differently with living organisms.
Classically, asymmetric synthesis utilising racemic substrates is limited to achieving a maximum yield of 50% (e.g., kinetic
resolutions). Enantioconvergent catalysis avoids this limitation with both enantiomers of the starting material being
converted into a single enantioenriched product, thanks to complex stereoablative or stereomutative de-racemisation
processes. This project will establish a conceptually new stereoretentive-dimerisation approach that results in both
enantiomers of the starting material being incorporated into the product with no de-racemisation required. This new concept
will prove highly valuable for the synthesis of small enantiopure building blocks, which will be of high value in many areas of
synthesis, and also for more complex late-stage transformations in complex molecule synthesis. Several approaches will
be pursued to demonstrate proof-of-principle, and applications in the synthesis of complex natural and unnatural products
will then be used to demonstrate the potential of stereoretentive-enantioconvergent catalysis in target-orientated synthesis.

Planned Impact

Catalysis is an inherently transformative field and the single most powerful method to reduce cost, energy demand and ensure sustainable fine and commodity chemical manufacture. On a grander scale, we will advance the UK economy, security and health through the development and understanding of catalysis. Through an intensive training programme we will ensure optimal use and recovery of our critical resources, exploit new long-term sustainable resources and feedstocks and will make chemical manufacture fit for future generations. Above all we will develop technologies offering a step-change in resource management and utilization. Specific impacts include:
Industry: The UK is an emerging leader in chemical sustainability. Critical Resource Catalysis is thus inherent to the growth of a technology-driven UK economy. In 2007, the growing chemical industry supported 6 million jobs and 21% of the UK GDP. World-class academic researchers, a broadly educated PhD cohort, inherent industrial collaboration and a holistic training environment will deliver unique individuals and scientific outputs for the chemical industry and beyond. Over 95% of our PhD students have continued their scientific efforts, sharing expertise in postdoctoral and industry positions: we produce exceptionally valued workers. The enhanced training provision provided by this CDT ensures even greater demand. Our training is intrinsically linked to industry and private sector parties, delivering core scientific knowledge and translational skills. With expertise in delivering critical innovations to industry, CRITICAT will become the hub for business and industry collaboration, consultation and discovery in the UK and beyond.
Policymakers: Global governments are recognising how important resources are to quality of life. The UK is committed to policies that demand the development of new technologies to facilitate a sustainable lifestyle, including the decarbonisation of energy supplies and the recycling of products, in particular those which contain a critical resource. With a cohort versed in the scientific and sociological arguments surrounding these issues further equipped to tackle future scientific challenges we will supports and strengthens the policies set out by the UK government and will serve as a champion for clear policy direction in the future.
Public: Educating not only our cohort but the general public about the importance of Critical Resource Catalysis is essential. We will engage with beneficiaries, from general audiences to UK HEIs, on our finite resources, their economic impacts and the societal benefits of a sustainable chemical industry. Public science demonstrations, focusing on the chemistry and engineering of critical resources, their uses in today's leading technologies, and the exploitation of the catalytic chemical sciences in a sustainable lifestyle will be led by the cohort to provide the public with a balanced and reasoned view of our contributions. With extensive expertise in public engagement, our team of educators and leaders will drive engagement activities forward and train our cohorts to develop as broad-skilled champions of chemistry and catalysis.
Dynamic researchers: This CDT will deliver at least 80 newly qualified PhD scientists and engineers who are trained in catalysis, the key driver behind sustainable chemical technologies. The students will undertake an exceptionally broad training regime enhanced well beyond a traditional PhD programme. Combined with state-of-the-art research projects, the collaborative interactions intrinsic throughout the CDT will yield great foundational and transferable skills for both researchers and institutions. They will learn business, managerial and communication skills from bespoke training, collaborative science and industry placements. Long-term impact will be ensured through our cohorts' entry into the global workforce and our universities commitment to improved collaboration and pedagogy.

Publications

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