Catalytic C-H Activation and Boronic Acid Synthesis

描述：申请者描述)烷基和芳基硼酸起作用 在药物化学中的重要作用。目前已经商业化了 基于硼酸和硼化合物的传感应用 抑制蛋白酶和治疗胶质母细胞瘤的有趣活性 通过硼中子俘获疗法(BNCT)。硼化合物可以制造多种不同的 在温和的条件下可以进行转换。因此，它们非常适合 对药物发现至关重要的组合方法。在这方面， 烷基或芳基硼酸与金属催化的交叉偶联反应 烷基或芳基卤化物已得到广泛应用。目前，组合式 交叉耦合反应可访问的空间受 可利用的硼酸。如果可以扩大硼酸的范围 与商业上使用的烷基和芳基卤化物的多样性相抗衡 可用，可通过碳-碳接触的化合物的数量 耦合度可以增加25倍。 硼酸偶联剂在药物合成中的大规模应用 目前正在开发中。生产硼酸最经济的途径 需要芳基氯化物作为合成子。考虑到对环境的担忧 与氯化芳香烃相关的根本新化学 取消了对氯化芳香族前体的要求 废物处理问题。 这项建议旨在将最新的催化化学应用于 由芳香烃和硼烷合成硼酸酯。在……里面 特别是，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, 该反应唯一的副产物是氢气，它是清洁和 很容易转化为水。重要的是，提议的方法需要 热激活；因此，所需的低温条件 避免了传统的金属化反应。官能团的广度 将检查容忍度，控制选择性的方法包括 建议。因为大规模应用程序最终将需要更强大的 提出了提高催化剂稳定性的策略。

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.