Catalytic C-H Activation and Boronic Acid Synthesis

催化C-H活化和硼酸合成

• 批准号: 6323947
• 负责人: Milton Rudolph Smith
• 金额: $ 20.2万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6323947
• 关键词: boronic acids; catalyst; chemical stability; combinatorial chemistry; cycloalkene; thermostability

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.

描述：申请人的描述）烷基和芳基硼酸发挥作用 重要的Rolesin药物化学。目前有商业化 基于硼酸和硼化合物的传感应用具有 蛋白酶抑制和治疗Gliboplastoma的有趣活动 通过硼中子捕获疗法（BNCT）。硼化合物范围很广 在轻度条件下可访问的转换。因此，他们非常适合 与药物发现核心的组合方法。在这方面， 烷基或芳基硼酸与金属催化的交叉偶联反应与 烷基或芳基卤化物已广泛应用。目前，组合 交叉耦合反应可访问的空间受到 硼酸的可用性。如果可以扩展硼酸的范围 竞争商业上烷基和芳基卤化物的多样性 可用，可通过碳碳获取的化合物数量 耦合可以增加25倍。 硼酸耦合用于药物合成的大规模应用 目前正在开发。硼酸最经济的途径 需要芳基氯作为合成子。考虑到环境问题 与氯化芳香剂相关，从根本上讲是新的化学物质 消除对氯化芳族前体的要求将减轻 废物处理问题。 该提议针对的是将最近的催化化学应用于 来自芳族碳氢化合物和硼烷的硼酸酯的合成。在 特别是，金属催化的C-H激活消除了对 芳基硼酸合成中的氯化芳族烃。此外， 反应的唯一副产品是氢气，它干净整洁， 容易转换为水。重要的是，拟议的方法需要 热激活；因此，需要的低温条件 避免了传统的金属反应。功能组的广度 将检查公差，控制选择性的方法是 建议的。由于大规模应用最终将需要更健壮的应用 还提出了催化剂，改善催化剂稳定性的策略。