Electrochemical Flow Processes for Ni-Catalysed Coupling Reactions

镍催化偶联反应的电化学流动过程

• 批准号: 2750460
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2750460
• 关键词: Electrochemical; Flow; Processes; Ni; Catalysed

Reductive cross-coupling/cross-electrophile coupling reactions are powerful synthetic tools which have gained significant attention with the development of Ni-catalysed processes (Fig. 1a). Many of these happens through single electron transfers (SETs) and radical intermediates, which enable access to different reactivity to those of traditional Pd-catalysed coupling reactions, e.g. coupling with sp3 partners with retention of stereochemistry. Their main drawback, which restricts scaled-up processes, is the need for stoichiometric reductant, e.g. Zn and Mn, and subsequent problems associated with cost and waste. Organic reductants, such as PPh3, tetra(dimethylamino)ethylene (TDAE) and HNiPr2, have been shown to work on lab-scale, although their recycling has not been explored in the literature. Scaling up reactions using Zn or zinc reagents remains difficult.Electrochemical methods present a possible solution to this problem. The reductant with finely tuned redox potential may be electrochemical recycled in situ, changing its role to a redox mediator. Alternatively, Ni-intermediates may undergo SET directly at the electrodes, bypassing the reductant altogether. A sacrificial reductant is still needed on the opposite electrode, but these allow significant flexibility in its redox potential. Some early successes with organic reductants have been reported, but process understanding and development in this area has yet to be taken up by the wider community.In this project, we aim to develop electrochemical flow processes to enable Ni-catalysed reductive coupling reactions and to generate the required process understanding for their further development. This will be achieved through the following objectives:O1: Development of electrochemical recycling processes for inorganic and organic reductants, e.g. TDEA.O2: Exploration of sacrificial reductant on anode and flow reactor designs.O3: Development of Ni-catalysed reductive decarboxylative cross coupling with electrochemical flow reactors (EFRs). O1 and O2 will directly address the various aspects of process development of Ni-catalysed reductive cross coupling and enable the use of redox mediators, which have been successfully employed in oxidative electrochemical processes by Stahl and co-workers. O3 is aimed at applying the process understanding gained in O1 and O2 to completely circumvent the need for a reductant by substituting it with the readily available carboxylate coupling partner. This is currently feasible with photochemistry, but a flow electrochemical process will be easier to control and more energy efficient.The project will take advantage of the expertise in EFRs (Bao Nguyen - BN, Charlotte Willans - CEW, Nikil Kapur - NK), catalysis (BN, CEW), electrochemical activation of zinc (BN), alternating polarity (AP) developed in the iPRD (NK), and the self-optimised electrochemical flow platform (CEW, NK) at Leeds. It will deliver the following: (i) in-depth understanding of the redox chemistry and recycling possibility of a wide range of reductants for reductive cross-coupling; (ii) EFRs and process designs for Ni-catalysed reductive coupling reactions; (iii) electrode kinetics and understanding of the influence of electrode material, solvent, voltage and current density, and (iv) electrochemical flow decarboxylative coupling reactions with Ni-catalysts.

还原性交叉偶联/交叉亲电试剂偶联反应是强大的合成工具，随着镍催化工艺的发展而获得了极大的关注（图1a）。其中许多通过单电子转移（SET）和自由基中间体发生，这使得能够获得与传统Pd催化的偶联反应不同的反应性，例如与sp3配偶体偶联并保留立体化学。它们的主要缺点是需要化学计量的还原剂，例如Zn和Mn，以及与成本和浪费相关的后续问题，这限制了放大的方法。有机还原剂，如PPh 3，四（二甲氨基）乙烯（TDAE）和HNiPr 2，已被证明在实验室规模的工作，虽然他们的回收利用还没有在文献中探索。使用锌或锌试剂的放大反应仍然是困难的，电化学方法提出了一个可能的解决这个问题的方法。具有微调的氧化还原电位的还原剂可以原位电化学再循环，将其作用改变为氧化还原介体。或者，Ni中间体可以直接在电极处经历SET，完全绕过还原剂。在相对电极上仍然需要牺牲还原剂，但这些允许其氧化还原电位的显著灵活性。一些早期的成功与有机还原剂已经报道，但过程的理解和发展在这一领域还没有采取更广泛的community.In这个项目中，我们的目标是开发电化学流动过程，使镍催化还原偶联反应，并产生所需的过程理解，为他们的进一步发展。这将通过以下目标实现：O 1：开发无机和有机还原剂的电化学回收工艺，例如TDEA。O2：探索阳极和流动反应器设计上的牺牲还原剂。O3：开发镍催化还原脱羧与电化学流动反应器（EFR）的交叉耦合。O 1和O2将直接解决镍催化还原交叉偶联工艺开发的各个方面，并使氧化还原介体的使用成为可能，斯塔尔及其同事已成功地将其用于氧化电化学过程。O3旨在应用在O 1和O2中获得的工艺理解，通过用容易获得的羧酸酯偶联伴侣取代还原剂来完全避免对还原剂的需求。这在目前的光化学中是可行的，但流动电化学过程将更容易控制，更节能。（Bao Nguyen - BN，夏洛特威兰斯- CEW，尼什卡普尔- NK），催化（BN，CEW），锌的电化学活化（BN），在iPRD中开发的交替极性（AP）（NK），以及利兹的自我优化电化学流动平台（CEW，NK）。它将提供以下服务：（i）深入了解氧化还原化学和各种还原剂用于还原性交叉偶联的回收可能性;（ii）镍催化还原偶联反应的EFR和工艺设计;（iii）电极动力学和对电极材料，溶剂，电压和电流密度影响的理解，以及（iv）镍催化剂的电化学流动脱羧偶联反应。