Recyclable Catalyst Technology for Cross-Coupling Reactions at Manufacturing Scale

基于诺贝尔奖获奖方法的均相钯 (Pd) 交叉偶联已成为生产增强生命的药物和化学品的关键（预计行业价值：>100 亿英镑）。然而，存在环境和可持续性问题，通常可以通过非均相钯催化剂来解决，但性能会降低。该项目通过开发广谱“捕获和释放”交叉偶联技术，结合了每种钯催化的优点。新型功能化二氧化硅材料将通过临时捕获非均相形式的钯催化剂来纯化反应产物，并能够通过新的反应组分以活性形式释放回溶液中以进行进一步生产。该技术以半连续形式采用，可应用于多个过程工业。将展示其在药品和农用化学品制造方面的初步应用。该项目严格符合 TSB 竞赛“为流程工业提供可持续制造”的总体目标，并描述了一种创新的“新颖催化”方法。这是通过一项技术实现的，该技术能够从现有的批量加工转变为半连续加工，并开发本质上更可持续的工艺，回收和再利用活性催化剂（包括金属和配体），同时大大降低后续产品纯化要求。总体目标是在二氧化硅固体载体上识别和优化适当官能化的芳基溴，以有效捕获并释放活性钯催化剂，并将其作为成熟的技术应用于制造。我们的联盟将配体设计/固定和对金属催化偶联的理解方面的学术和中小企业专业知识与全球工业产品最终用户联系起来。过渡金属 (Pd) 交叉偶联反应在各种化学相关行业中的广泛应用意味着，随着英国努力加快生产流程以提高其在制造业的竞争优势，所选择的主题材料具有高度的话题重要性。该项目将均相钯催化的优点（反应速度快、选择性和灵活的催化剂选择）与使用固相暂时支撑活性钯催化剂（以便随后再利用）相结合，同时允许轻松的产品纯化，将通过半连续处理实现高效化学合成，并提高产量。首先开发然后微调二氧化硅支撑的连接体以适当地影响交叉偶联反应步骤，这对于行业采用最终商业产品作为工艺规模交叉偶联的广谱、首选方法至关重要；该项目的活动和目标反映了这一点。这种创新和改进的交叉偶联催化路线的产出将通过更好的工艺经济学来观察，通过回收高成本的合成金属（包括钯）和有机配体，并减少有毒废物的产出。端点商业产品将引起国际兴趣并导致出口销售。总之，我们的项目主要侧重于催化工艺创新，通过在催化循环中引入非均相阶段（同时也作为反应纯化步骤）来提高交叉偶联用钯催化剂的寿命和回收利用。

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.