Recyclable Catalyst Technology for Cross-Coupling Reactions at Manufacturing Scale

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Homogeneous Palladium (Pd) cross-couplings, based on Nobel-prize winning methodologies, have become essential forthe production of life-enhancing pharmaceuticals & chemicals (est. worth to sector: >£10 bn). However there areenvironmental & sustainability issues, often addressed by heterogeneous Pd catalysts but with reduced performance. Thisproject combines the advantages of each type of Pd catalysis by development of a broad-spectrum 'Catch & Release'cross-coupling technology. Novel functionalised silica materials will allow purification of reaction products by temporarycapture of the Pd catalyst in heterogeneous form, capable of release back in it's active form into solution by new reactioncomponents for further production. The technology is employed in semi-continuous format, with application possible acrossmultiple process industries. Initial applications towards the manufacture of pharmaceuticals & agrochemicals will bedemonstrated. This project fits rigorously within the TSB competition's headline goal of providing 'Sustainablemanufacturing for the process industry' and describes an innovative 'Novel Catalysis' approach. This is delivered through atechnology which enables change from existing batch to semi-continuous processing and the development of inherentlymore sustainable processes, which recover & reuse the active catalysts, both metal and ligand, whilst dramatically reducing subsequent product purification requirements. The overarching objective is the identification and optimisation of anappropriately functionalised aryl bromide on the silica solid support to effectively catch & then release the active Pd catalystand to take this as proven technology into manufacture.Our consortium links academic and SME expertise in ligand design/immobilisation and understanding of metal-catalysedcouplings together with global industrial product end-users. The widespread application of transition metal (Pd) crosscouplingreactions in a variety of chemistry-related industries means the chosen subject material is of high and topicalimportance as the UK strives for faster production processes to increase it's competitive edge in manufacturing. Theproject's combination of the benefits of homogeneous Pd catalysis (fast reaction rates, selectivity and flexible catalystchoice) with the use of a solid phase to temporarily support the active Pd catalyst (for subsequent reuse) & simultaneouslyallow easy product purification will enable high efficiency chemical synthesis with increased throughput by semi-continuousprocessing. First development and then fine-tuning of the silica-supported linker to suitably effect the cross-couplingreaction step is critical to industry adoption of the final commercial product as a broad-spectrum, preferred method forcross-coupling at process scale; the project's activities and objectives reflect this. The output from this innovative andimproved catalytic route for cross-couplings will be observed by better process economics, through recycling of high costsynthetic metals, including Pd, and organic ligands, and reduced toxic waste outputs. The endpoint commercial productwould generate international interest and lead to export sales. In summary, our project focuses primarily on catalysisprocess innovation, through improvement of the lifetime and recycling of the Pd catalyst for cross-couplings by theintroduction of a heterogeneous stage to the catalytic cycle, which also serves as a reaction purification step.