Direct Functionalization of Heteroarenes using Phosphorus

直接官能化将化学惰性的C-H键转化为化学可塑的C-R键（R = B、C、N、O、Cl、Br、I）。以这种方式控制功能化在合成科学中非常重要，因为它为无数人造产品创造了必要的构建模块，从药物到聚合物，电子产品和农用化学品。实现这种转化的催化剂主要基于昂贵的不可再生贵金属，包括钯和铱，其来源具有重大的环境和地缘政治问题。寻找基于廉价和地球丰富的p区元素（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-块簇提供的多个配位位点，在一个方便的步骤中催化包括吡啶在内的杂芳烃的直接官能化。约60%的FDA批准的药物单独功能的氮杂环，如pyridine.Preliminary结果：我们已经制备和表征的第一个例子的硼官能化基团15 Zintl簇。发现化合物1对于以选择性1，4-方式在吡啶上加成H-B键、硼氢化是非常活性的催化剂。有趣的是，还发现在反应的水性后处理时，吡啶被重整并且H2气体被消除。这些结果表明，簇合物可以作为催化剂在吡啶上添加H-B键，并且再芳构化和H2消除是强驱动力。在该硼氢化转化中的再芳构化是不期望的。我们能把这个消极的转变成积极的吗？假设：在我们的初步结果中，在水处理后，我们失去了在催化硼氢化过程中安装的氢化物。但如果安装了除氢化物以外的亲核试剂，并且在重排过程中失去了一个H原子，则我们将C-H键置换为C-R键。与其他将杂芳烃上的C-H键转化为C-R键的催化剂相比，我们的催化剂基于廉价且可持续的p-区元素磷。多聚磷簇合物是一种具有吸引力的催化剂平台，因为它们可以与多相材料赤磷在结构上相关联。[6]赤磷是非常便宜和可持续的，但很难研究。用[P7]团簇建立的催化转化将扩展到更大的聚磷球，例如[P16]和[P21]系统，然后用赤磷本身。研究与分子簇允许在原位研究，反应优化，和mechanistic investigations。同时，基于赤磷的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官能化的催化剂。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]催化剂活化磷/硼基簇合物的B-R键。目标B：使用吡啶作为原型，关闭催化循环并优化催化条件。目标C：开发更大聚磷材料的催化。提供的培训：多核NMR、XRD衍射、计算化学、惰性气氛合成、有机金属化学和机理研究。

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.