Catalytic C-H Activation and Boronic Acid Synthesis

烷基和芳基硼酸起作用 在药物化学中的重要作用。目前已经商业化 基于硼酸和硼化合物的传感应用已经 用于蛋白酶抑制和用于治疗胶质母细胞瘤的令人感兴趣的活性 硼中子俘获疗法（BNCT）硼化合物可以产生各种各样的 在温和条件下可进行的转化。因此，他们非常适合 组合方法是药物发现的核心。在这方面 金属催化的烷基或芳基硼酸与 烷基或芳基卤化物已被广泛应用。目前，组合 可用于交叉偶联反应的空间受到 硼酸的可用性。如果硼酸的范围可以扩大 以与商业上使用的烷基和芳基卤化物的多样性相竞争， 可用的，通过碳-碳可获得的化合物的数量 耦合可以增加25倍。 硼酸偶联在药物合成中的大规模应用 目前正在开发中。硼酸的最经济途径 需要芳基氯作为取代基。考虑到环境问题 与氯代芳香族化合物有关，这是一种全新的化学物质， 消除了对氯化芳香族前体的需求， 废物处理问题。 该建议的目标是最近的催化化学应用于 由芳烃和硼烷合成硼酸酯。在 特别地，金属催化的C-H活化消除了对 芳基硼酸合成中的氯代芳烃。此外，本发明还提供了一种方法， 反应的唯一副产物是氢气，氢气是清洁的， 很容易转化为水。重要的是，拟议的方法需要 热活化;因此， 避免了传统的金属间化合物反应。功能群宽度 将检查耐受性，控制选择性的方法是 提出了由于大规模应用最终需要更强大的 催化剂，改善催化剂稳定性的策略也被提出。

DESCRIPTION: Applicant's Description) Alkyl and arylboronic acids play important rolesin medicinal chemistry. There are presently commercialized sensing applications based on boronic acids and boron compounds have interesting activities for protease inhibition and for treating gliboplastoma via boron neutron capture therapy (BNCT). Boron compounds make a wide range of transformations accessible under mild conditions. Thus they are well suited to combinatorial methods that are central to drug discovery. In this regard, the metal catalyzed cross-coupling reactions of alkyl or arylboronic acids with alkyl or aryl halides have been broadly applied. Presently, the combinatorial space that is accessible to cross-coupling reactions is limited by the availability of boronic acids. If the range of boronic acids could be expanded to rival the diversity of alkyl and aryl halides that are commercially available, the number of compounds that is accessible through carbon-carbon coupling could be increased by twenty-five fold. Large-scale applications of boronic acid couplings for pharmaceutical synthesis are currently being developed. The most economical route to boronic acids requires aryl chlorides as synthons. Given the environmental concerns associated with chlorinated aromatics, fundamentally new chemistry that eliminates the requirement for chlorinated aromatic precursors would alleviate waste disposal problems. This proposal targets the application of recent catalytic chemistry to the synthesis of boronic esters from aromatic hydrocarbons and boranes. In particular, the metal-catalyzed C-H activation eliminates the need for chlorinated aromatic hydrocarbons in aryl boronic acid synthesis. In addition, the only by-product of the reaction is hydrogen gas, which is cleanly and easily converted to water. Importantly, the proposed methodology requires thermal activation; thus, the cryogenic conditions that are required for traditional metallation reactions are avoided. The breadth of functional group tolerance will be examined, and approaches to controlling selectivity are proposed. Since large scale applications will ultimately require more robust catalysts, strategies for improving catalyst stability are also presented.