Recyclable Catalyst Technology for Cross-Coupling Reactions at Manufacturing Scale

均相钯(Pd)交叉偶联，基于诺贝尔奖获得者方法学，已成为提高生命的药物和化学品(EST)生产的关键。对行业的价值：&gt；GB 100亿)。然而，存在环境和可持续性问题，通常由多相Pd催化剂解决，但性能降低。该项目通过开发广谱的“捕捉-释放”交叉耦合技术结合了每种类型的钯催化剂的优点。新型功能化二氧化硅材料将允许通过暂时捕获非均相形式的钯催化剂来提纯反应产物，能够通过新的反应成分将其以活性形式释放回溶液中以供进一步生产。该技术以半连续形式应用，可能应用于多个流程行业。将展示在制药和农用化学品制造方面的初步应用。该项目严格符合TSB竞赛的标题目标，即为流程工业提供“可持续的制造”，并描述了一种创新的“新型催化”方法。这是通过一种技术实现的，该技术能够从现有的批量处理改变为半连续处理，并开发固有的更可持续的工艺，回收和再利用活性催化剂，包括金属和配体，同时大幅减少后续产品的净化要求。我们的首要目标是确定和优化二氧化硅固体载体上适当功能化的芳基溴，以有效地捕捉并释放活性钯催化剂，将其作为成熟的技术投入生产。我们的联盟将学术和中小企业在配体设计/固定化方面的专业知识和对金属催化偶联的理解与全球工业产品终端用户联系在一起。过渡金属(PD)交叉偶合反应在各种化学相关行业中的广泛应用意味着，在英国努力提高生产过程以提高其在制造业中的竞争优势之际，所选的主题材料具有高度和局部的重要性。该项目将均相钯催化的优点(快速反应、选择性和灵活的催化剂选择)与使用固相临时支撑活性钯催化剂(以便后续重复使用)相结合，同时允许容易的产品提纯，将通过半连续工艺实现高效的化学合成，并增加产量。首先开发二氧化硅支撑的连接物，然后对其进行微调，以适当地影响交叉偶联反应步骤，这对于工业采用最终商业产品作为过程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。通过回收高成本的合成金属，包括钯和有机配体，以及减少有毒废物的产生，将通过更好的工艺经济性来观察这种用于交叉偶联的创新和改进的催化路线的输出。终端商业产品将引起国际兴趣，并带动出口销售。总而言之，我们的项目主要关注催化工艺创新，通过在催化循环中引入多相阶段来提高交叉偶联用Pd催化剂的使用寿命和回收利用，这也是一个反应净化步骤。

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.