Synthesis, the science of making molecules, is central to human wellbeing through its ability to produce new molecules for use as medicines and materials. Every new drug, whether an antibiotic or a cancer treatment, is based on a molecular structure designed and built using the techniques of synthesis. Synthesis is a complex activity, in which bonds between atoms are formed in a carefully choreographed way, and training to a doctoral level is needed to produce scientists with this expertise. Irrespective of the ingenuity of the synthetic chemist, the complexity of synthetic endeavours means that they are often the pinch point in the development of a new product or the advance of new molecular science. In addition, synthesis can no longer rely on intensive use of human, material, and time resources, and creative solutions to ways of making molecules faster, more efficiently, using less energy, and avoiding rare to toxic metals are urgently needed. Recent developments in digital chemistry (eg reaction technology and automation, data collection & analysis, machine learning & artificial intelligence, computation & molecular design, and the use of virtual reality) now make possible a fundamental change in the way molecular targets are identified and synthesis is carried out. The chemical and pharmaceutical discoveries which underpin a major sector of the UK's economy are almost entirely dependent on synthesis, and our industrial partners see an urgent need for a new generation of employees who combine cutting-edge chemical synthesis expertise with the state-of-the-art digital skills that are set to revolutionise the field. We therefore propose a CDT that will train students to carry out world-leading chemical synthesis at the University of Bristol, the UK's top institution for chemistry research (REF2021), with their creativity and productivity being enhanced by an initial 8-month Digital Chemistry (DC) training focus that un-derpins a subsequent 3 1/4 year PhD project. The training will be delivered in the form of a set of modules that embody key aspects of DC such automation, algorithm-driven optimisation, photochemistry, electrochemistry and flow chemistry supported by training in the techniques of machine learning and data analysis. These activities will be applied to current synthetic challenges in two short immersive 'mini-projects' in research labs and will feed into a PhD research project in an area of synthetic chemistry that is underpinned by the application of digital chemistry methods. The focus of the CDT aligns with Bristol's global reputation in chemical synthesis and computation, and in its current investment in digital chemistry as a strategic research direction. Bristol Chemistry has enviable success in spinout companies, and alongside ongoing training in professional development skills we aim to cultivate an entrepreneurial ethos by partnering with local start-up partners to provide immersive workshops, placements, network links and mentorship to nurture future spin-outs by CDT students. We will build on lessons learnt from delivering previous successful CDTs in Chemical Synthesis, and we will continue to develop our recruitment, training & research opportunities in line with best practice for Equity, Diversity & Inclusion, applying more widely lessons from the evolution that has allowed the diversity of our applicant team to be reflected in the ~50/50 M:F and ~25% minority ethnic composition of our management committee. Our evolved CDT will build on our unrivalled depth of experience to train diverse cohorts of creative and entrepreneurial experts in chemical synthesis, skilled in modern aspects of technology & data science. Our graduates will be uniquely prepared as research pioneers in the ever-changing scientific and industrial landscape of the chemical sciences that continue to underpin this country's prosperity.

Synthesis, the science of making molecules, is central to human wellbeing through its ability to produce new molecules for use as medicines and materials. Every new drug, whether an antibiotic or a cancer treatment, is based on a molecular structure designed and built using the techniques of synthesis. Synthesis is a complex activity, in which bonds between atoms are formed in a carefully choreographed way, and training to a doctoral level is needed to produce scientists with this expertise. Our proposed CDT is tailored towards training the highly creative, technologically skilled scientists essential to the pharmaceutical, biotech, agrochemical and materials sectors, and to many related areas of science which depend on novel molecules. Irrespective of the ingenuity of the synthetic chemist, synthesis is often the limiting step in the development of a new product or the advance of new molecular science. This hurdle has been overcome in some areas by automation (e.g. peptides and DNA), but the operational complexity of a typical synthetic route in, say, medicinal chemistry has hampered the wider use of the technology. Recent developments in the fields of automation, machine learning (ML), virtual reality (VR) and artificial intelligence (AI) now make possible a fundamental change in the way molecules are designed and made, and we propose in this CDT to engineer a revolution in the way that newly trained researchers approach synthetic chemistry, creating a new generation of pioneering innovators. Making use of Bristol's extensive array of automated synthetic equipment, flow reactors, peptide synthesisers, and ML Retrosynthesis Tool, students will learn and appreciate this cutting-edge technology-driven program, its potential and its limitations. Bristol has outstanding facilities, equipment and expertise to deliver this training. At its core will be a state-of-the-art research experience in our world-leading research groups, which will form the majority of the 4-year CDT training period. For the 8 months prior to choosing their project, students with complete a unique, multifaceted Technology & Automation Training Experience (TATE). They will gain hands-on experience in advanced techniques in synthesis, automation, modelling and virtual reality. In conjunction with our Dynamic Laboratory Manual (DLM), the students will also expand their experience and confidence with interactive, virtual versions of essential experimental techniques, using simulations, videos, tutorials and quizzes to allow them to learn from mistakes quickly, effectively and safely before entering the lab. In parallel, they will develop their teamworking, leadership and thinking skills through brainstorming and problemsolving sessions, some of them led by our industrial partners. Brainstorming involves the students generating ideas on outline proposals which they then present to the project leaders in a lively and engaging interactive feedback session, which invariably sees new and student-driven ideas emerge. By allowing students to become fully engaged with the projects and staff, brainstorming ensures that students take ownership of a PhD proposal from the start and develop early on a creative and collaborative atmosphere towards problem solving. TATE also provides a formal assessment mechanism, allow the students to make a fully informed choice of PhD project, and engages them in the use of the key innovative techniques of automation, machine learning and virtual reality that they will build on during their projects. We will integrate into our CDT direct interaction and training from entrepreneurs who themselves have taken scientific ideas from the lab into the market. By combining our expertise in synthesis training with new training platforms in automation, ML/AI/VR and entrepreneurship this new CDT will produce graduates better able to navigate the fast-changing chemical landscape.