{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/293977"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/293977","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"High-Throughput Methods For Reaction Development Using The Mosquito® Liquid Handling Robot","abstract":"High-throughput technologies have dramatically advanced processes such as drug screening and protein crystallisation. Application of related high-throughput experimentation practices have the potential to revolutionise chemical synthesis. This thesis describes the standardisation and implementation of high-throughput protocols in the Gaunt group using the Mosquito® liquid-handling robot. An automated high-throughput protocol was established for quantitative data generation. The Chan-Lam reaction of an amine and aryl boronates was used as an initial proof-of-concept reaction to standardise the high-throughput protocol. All parts of the protocol were optimised including the creation of an Excel spreadsheet and Mosquito® dosing protocols. Quantitative data was achieved using high-throughput LCMS analysis with internal standards and calibration curves. Data were tested by statistical methods integrated into the Excel Spreadsheet. Using the standardised high-throughput protocol, reaction conditions for the Chan-Lam were assessed using multi-parallel arrays. A total of 30 boronic esters were screened against eight bases, six copper catalysts and two ligands, totaling 5,888 reactions. All reaction components were parameterised using experimental and computational descriptors to generate a predictive model, in collaboration with computational chemists. To rapidly triage reaction conditions, high-throughput TLC was developed. 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