Direct Functionalization of Heteroarenes using Phosphorus

使用磷直接官能化杂芳烃

• 批准号: 2752689
• 金额: --
• 依托单位: University of Manchester
• 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-2752689
• 关键词: Direct; Functionalization; Heteroarenes; using; Phosphorus

Direct functionalization converts chemically inert C-H bonds into chemically malleable C-R bonds (R = B, C, N, O, Cl, Br, I). Controlled functionalization in this manner is highly important in synthetic science, as it creates the building blocks necessary for countless man-made goods, from pharmaceuticals to polymers, electronics and agrochemicals. Catalysts that enable this transformation are largely based on expensive nonrenewable precious metals, including palladium and iridium, sourcing of which has significant environmental and geopolitical issues. Finding sustainable alternatives based on cheap and earthabundant p-block elements, including phosphorus, has become increasingly urgent. We propose exploiting the multiple coordination sites offered by p-block clusters to catalyze the direct functionalization of heteroarenes, including pyridine, in one convenient step. About 60% of FDA approved pharmaceuticals alone feature a nitrogen heterocycle, such as pyridine.PRELIMINARY RESULTS: We have prepared and characterized the first example of a boron functionalized group 15 Zintl cluster. Compound 1 was found to be a very active catalyst for the addition of H-B bonds, hydroboration, across pyridines in a selective 1,4-fashion. Interestingly, it was also found that upon aqueous work-up of the reaction, the pyridine was reformed and H2 gas eliminated. These findings reveal that clusters can act as catalysts to add H-B bonds across pyridines, and re-aromatization and H2 elimination are strong driving forces. Re-aromatization in this hydroboration transformation is undesirable. Can we turn this negative into a positive? HYPOTHESIS: In our preliminary results, upon aqueous work-up we lose the hydride installed during the catalytic hydroboration. But if a nucleophile other than hydride is installed, and an H atom lost during rearomatization we would metathesis a C-H bond for a C-R bond. Compared to other catalysts that convert C-H bonds to C-R bonds on heteroarenes, our catalysts are based on the cheap and sustainable p-block element phosphorus. Polyphosphorus clusters are attractive platforms as catalysts because they can be structurally related to the heterogenous material red phosphorus.[6] Red phosphorus is very inexpensive and sustainable, but difficult to study. Catalytic transformations established with [P7] clusters will be extended to larger polyposphides, for example [P16] and [P21] systems, and then with red phosphorus itself. Studies with the molecular clusters allow for in situ studies, reaction optimizations, and mechanistic invesigations. While, red phosphorus-based catalysts open the door to industry translation and high recyclability / stability. OVERALL AIM: Establish phosphorus-based materials as catalysts for direct functionalization of heteroarenes.We will achieve our overall aim by meeting three Objectives:Objective A: Using [P7] catalysts activate B-R bonds with phosphorus/boron-based clusters.Objective B: Using pyridines as a prototype, close the catalytic cycle and optimize catalytic conditions.Objective C: Develop catalysis with larger polyphosphorus materials.TRAINING OFFERED: multi-nuclear NMR, XRD diffraction, computational chemistry, inert-atmosphere synthesis, organometallic chemistry, and mechanistic studies.

直接官能化将化学惰性的C-H键转化为化学上可延展的C-R键(R=B、C、N、O、Cl、Br、I)。这种受控功能化在合成科学中非常重要，因为它为从药品到聚合物、电子产品和农用化学品的无数人造商品创造了必要的基础。促成这种转变的催化剂主要基于昂贵的不可再生贵金属，包括钯和铱，它们的来源存在重大的环境和地缘政治问题。寻找基于廉价和丰富的P-块元素(包括磷)的可持续替代品已变得越来越紧迫。我们建议利用p-嵌段簇提供的多个配位来催化包括吡啶在内的杂芳烃的直接官能化，一步完成。仅FDA批准的药物中就有约60%的药物含有氮杂环，如吡啶。初步结果：我们制备并表征了第一个硼功能化的第15族锌簇合物。化合物1被发现是以选择性的1，4-方式在吡啶上加成H-B键的非常活跃的催化剂。有趣的是，还发现在反应的水溶液中，吡啶发生了重整，消除了氢气。这些结果表明，团簇可以作为催化剂在吡啶上加成H-B键，而再芳构化和氢消除是很强的驱动力。这种氢化反应中的再芳构化反应是不可取的。我们能把这个负面的东西变成积极的东西吗？假设：在我们的初步结果中，在水中的工作，我们失去了氢化物安装在催化氢化硼。但是，如果安装了氢化物以外的亲核剂，并且在重芳构化过程中失去了一个H原子，我们就会将一个C-H键歧化为一个C-R键。与其他在杂芳烃上将C-H键转化为C-R键的催化剂相比，我们的催化剂是基于廉价和可持续的P-嵌段元素磷。多磷簇合物是很有吸引力的催化剂平台，因为它们可以在结构上与多相材料红磷相关。[6]红磷价格低廉，可持续发展，但研究难度很大。与[P7]簇建立的催化转化将扩展到更大的聚磷脂，例如[P16]和[P21]体系，然后与红磷本身。通过分子簇的研究，可以进行原位研究、反应优化和机理研究。同时，红磷基催化剂为工业转化和高可回收性/稳定性打开了大门。总体目标：建立磷基材料作为杂芳烃直接功能化的催化剂。我们将通过满足三个目标来实现我们的总体目标：目标A：使用[P7]催化剂激活具有磷/硼基簇合物的B-R键。目标B：以吡啶为原型，关闭催化循环，优化催化条件。目标C：开发更大的多磷材料的催化。提供：多核核磁共振、X射线衍射、计算化学、惰性气氛合成、有机金属化学和机理研究。