A Flow Process For Aminomethylations Using Catalysts Supported On Magnetic Nanoparticles

均相催化剂与非均相催化剂相比有几个优点；包括更大的选择性和可控性，因为它们的分子性质确保只有一种类型的活性位点存在。此外，据估计，85%的化学过程是催化进行的，多相催化与均相催化的应用比例约为75:25。然而，涉及均相催化的连续流过程存在困难，并且批处理中的许多高效系统不能转移到流动中。一个主要问题是如何从催化剂中分离产物。巴斯大学的研究小组最近制备了两种催化剂，一种是有机金属，另一种是超顺磁性氧化铁核心周围的金属外壳。初步结果表明，固定化的磺化膦或乙酸配体允许铑或钯配合物的配位，有效催化（高达100%的转化率）硼酸的共轭加成，Suzuki和Heck偶联，以及氢化和二羟基化反应。催化剂在磁分离后仍保持活性，在某些情况下甚至连续运行10次。在这个建议中，我们希望开发流动化学协议的钯催化偶联氨基烷基硼试剂使用新型的磁可移动和可回收的半均相催化剂。它们的大小意味着它们的作用方式与均相催化剂相同，但它们在磁场中很容易被回收。在明确强调开发广泛应用于药物化合物合成的方法的同时，我们将重点关注芳基/乙烯基卤化物的催化氨基甲基化，作为还原性胺化的战略替代方案。通常，纳米颗粒的磁性被用来促进与反应产物的分离。我们希望通过进一步开发磁性来扩展这一点，以(i)将纳米颗粒催化剂捕获在流动反应器的某些区域内；（ii）应用交变磁场来操纵和移动反应器周围的纳米颗粒，从而增强传质。这项新技术将提供许多优点，主要是均相催化剂在反应器中不需要与产品分离。

Homogeneous catalysts offer several advantages over their heterogeneous counterparts; including the greater selectivity and controllability because their molecular nature ensures that only one type of active site is present. Furthermore, it is estimated that 85% of all chemical processes are run catalytically, with the ratio of applications of heterogeneous to homogeneous catalysis of ca. 75:25.However, continuous flow processes involving homogeneous catalysis present difficulties and many efficient systems in batch processes cannot be transferred to flow. A major problem is associated with separating the products from the catalyst. The group at Bath has recently prepared two types of catalyst consisting of either organometallic species or a metallic shell around superparamagnetic iron oxide cores. Preliminary results indicate that immobilized sulfonated phosphines or acetate ligands allow the coordination of rhodium or palladium complexes that efficiently catalyse (up to 100% conversion) the conjugate addition of boronic acids, and Suzuki and Heck coupling, as well as hydrogenation and dihydroxylation reactions. The catalysts retained activity after magnetic separation, in some cases even after 10 consecutive runs. In this proposal we wish to develop flow chemistry protocols for the palladium-catalysed coupling of aminoalkylboron reagents using new types of magnetically moveable and recoverable semi-homogeneous catalysts. Their size means that they operate in the same manner as homogeneous catalysts but they are easily recovered in a magnetic field. With a clear emphasis on developing methodology of broad application to the synthesis of medicinal compounds, we will focus on the catalytic aminomethylation of aryl/vinyl halides as a strategic alternative to reductive amination. Normally the magnetic properties of the nanoparticles have been used to facilitate separation from the reaction product(s). We wish to extend this by further exploitation of the magnetism to (i) entrap the nanoparticle catalyst within certain regions of a flow reactor and (ii) to apply alternating magnetic fields to manipulate and move the nanoparticles around the reactor, enhancing mass transfer. This new technology will offer a number of advantages, chiefly entrapment of the homogeneous catalyst in the reactor without necessity of separation from products.