Carbon-Carbon Bond-Forming Reactions Via C-H Activation

通过 C-H 活化形成碳-碳键的反应

• 批准号: 6841955
• 负责人: JONATHAN A ELLMAN
• 金额: $ 32.1万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-05 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6841955
• 关键词: acylation; alkylation; carbon; catalyst; chemical bond; chemical reaction; chemical synthesis; drug design /synthesis /production; heavy metals; hydrogen; imines; method development; nitrogenous heterocyclic compound

DESCRIPTION (provided by applicant): Transition metal catalyzed carbon-carbon bond formation has become incredibly important for the synthesis of pharmaceutical agents, natural products and materials. Indeed, metal-catalyzed cross-coupling reactions and olefin metathesis are now some of the most heavily used reactions in organic synthesis. The importance of these transformations is in large part due to their broad functional group compatibility combined with the large and diverse array of readily available compounds that can serve as starting materials. Metal-catalyzed C-H bond activation followed by carbon-carbon bond formation also has the potential to become exceptionally powerful in organic synthesis. Several C-H activation processes, particularly those catalyzed by late transition metals, are highly functional group compatible. In addition, because virtually every organic compound contains C-H bonds, the availability of starting materials cannot be surpassed. However, the large majority of organic compounds contain multiple C-H bonds and therefore selective C-H bond activation is essential to the development of useful synthetic methods. In addition, catalysts must be identified that enable not only selective C-H activation, but also subsequent carbon-carbon bond formation. This proposal describes the development and application of powerful catalytic methods designed to achieve these goals. The proposed research can be divided into three specific aims. Three classes of synthesis methods will be developed: (1) Intramolecular ortho-alkylation of aromatic imines, (2) Alkylation of nitrogen heterocyles, (3) Acylation of nitrogen heterocycles. The substrate scope for each method will be established, and where appropriate enantioselective catalytic methods will be developed. The importance of each method will also be demonstrated by the synthesis of pharmacologically active agents.

描述（由申请人提供）：过渡金属催化的碳 - 碳键形成对于合成药品，天然产物和材料而变得非常重要。实际上，金属催化的交叉偶联反应和烯烃的分解是有机合成中一些最广泛使用的反应。这些转换的重要性在很大程度上是由于它们广泛的功能群兼容性以及可以用作起始材料的大量而多样的可用化合物。 金属催化的C-H键激活，然后是碳碳键的形成，也有可能在有机合成中变得异常强大。几种C-H激活过程，尤其是由晚期过渡金属催化的过程，具有高度功能性的组。此外，由于几乎每个有机化合物都包含C-H键，因此无法超过起始材料的可用性。但是，大多数有机化合物包含多个C-H键，因此选择性C-H键激活对于开发有用的合成方法至关重要。此外，必须确定催化剂不仅可以选择性C-H激活，还可以使碳碳键形成。该建议描述了旨在实现这些目标的强大催化方法的开发和应用。拟议的研究可以分为三个特定目标。 将开发三类的合成方法：（1）芳族芳基分子内的静脉内 - （2）（2）氮杂环的烷基化，（3）氮杂环的酰化。将建立每种方法的底物范围，并在适当的对映选择性催化方法的情况下。每种方法的重要性也将通过合成药理学活性药物的合成来证明。