Merging Hydrogen Borrowing/Transfer Catalysis with Photochemistry

Lead Research Organisation: University of Oxford


This project falls within the EPSRC Synthetic Organic Chemistry research area.

Hydrogen borrowing catalysis (HBC) has emerged as a powerful catalytic method for the synthesis of complex molecules. The one-pot oxidation-reduction sequence has an intrinsic high atom economy and alkylation reactions using alcohols (or amines) as feedstock molecules lead to the production of valuable products and water (or ammonia) as the sole by-product. This presents HBC as a green alternative to traditional alkylation chemistry. Unfortunately, HBC typically requires high operating temperatures, leading to poor selectivity with respect to other sensitive parts of the organic molecule of interest (poor functional group tolerance). An alternative way of giving a reaction enough energy to proceed without using such high temperatures is by using high-energy irradiation or from visible light- mediated photocatalysis.
Visible light-mediated photocatalysis (PC) has emerged as a powerful and safer alternative to high energy ultra violet light irradiation of organic molecules. Ultra-violet irradiation is extremely harsh and has poor functional group tolerance, meaning it is not suitable as a general method - visible light is significantly safer to operate with and more selective. Although many types of chemistry which can intercept the production of a short-lived oxidised molecules from HBC have been explored, using photochemistry to do so has not. In this project we will aim to combine the two technologies to produce complex organic molecules via tandem hydrogen borrowing/transfer photochemical reactions. Thereby deriving new chemical reactivity and also looking to avert the typically harsh conditions of HBC, creating a more generalised and applicable method which could be used by the pharmaceutical or agrochemical communities.
First we will investigate new modes of reactivity, such as the feasibility of creating a short-lived molecule, which is active to PC from a hydrogen-borrowing event (oxidation or reduction). This molecule could be excited by a photocatalyst and undergo a reaction with other organic molecules before a final hydrogen borrowing event (reduction or oxidation) can complete the catalytic cycle. Similarly, we will look to develop catalysts which could in principle perform both the hydrogen borrowing events and photochemical excitation of the organic molecules. To our knowledge, no groups have looked to merge HBC and PC, which in principle could transform the landscape of hydrogen borrowing chemistry in addition to discovering novel chemical reactivity.

Planned Impact

This programme is focused on a new cohort-driven approach to the training of next-generation doctoral scientists in the practice of novel and efficient chemical synthesis coupled with an in-depth appreciation of its application to biology and medicine.

This collaborative academic-industrial SBM CDT will have long-term benefit to the chemical industry, including the pharmaceutical, agrochemical and fine chemical sectors. These industries will benefit through: (i) the potential to employ individuals trained with broad and relevant scientific and transferable skills; (ii) new approaches to the investigation of complex biological and medical problems through novel chemistry; and (iii) better and more efficient synthetic methods.

We will link the work of DSTL, and our pharmaceutical and agrochemical partners (GSK, UCB, Vertex, Evotec, Eisai, AstraZeneca, Syngenta, Novartis, Takeda, Sumitomo and Pfizer) through a common theme of synthesis training. The design and synthesis of new compounds is essential for disease treatment and prevention, and for maintaining food security. Synthesis contributes significantly to UK tax revenue and results in sustained employment across a number of sectors. Employers in the finance, law, health, academic, analytical, government, and teaching professions, for example, also recognise the value of the translational skill-sets possessed by synthesis postgraduates, which this programme will provide.

The SBM CDT training programme will adopt an IP-free model to enable completely free exchange of information, know-how and specific expertise between students and supervisors on different projects and across different industrial companies. This will lead to better knowledge creation through unfettered access to information from all academics, partners and students involved in the project. By focussing on basic science, we will engender genuine collaboration leading to enabling technology that will be of use across a wide range of industries.

We will train the next generation of multidisciplinary synthetic chemists with an appreciation of the impact of synthesis in biology and medicine. Their unconstrained view of synthesis will aid in new scientific discoveries leading to new products, which (with appropriate inward investment), can lead to the formation of new companies and new UK employment.

We will, in part through an alliance with the Defence, Science and Technology Laboratory, engage with policy-makers to influence future policy issues involving chemistry such as food security and the rise of antibiotic resistance (both of which are relevant to our programme and are important for society as a whole).

Outreach and public engagement will be a key aspect of our programme; and all students in the proposed SBM CDT will take part in at least one outreach activity. Typical activities include: open days in the Chemistry Department through the 'Outreach Alchemists', engaging with the Oxfordshire Science Festival and participation in the various other activities already in place through the public engagement programme of the Department of Chemistry.

The research output of the students will be disseminated via high impact international publications and lectures; these will be of value to other academics in relevant fields and will be of value in the development of further research funding applications. Outreach activities and research output will also be advertised on a website dedicated to the proposed SBM programme.


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