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: 7157604
• 负责人: JONATHAN A ELLMAN
• 金额: $ 30.33万
• 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/7157604
• 关键词: Carbon; Bond; Forming; Reactions; Via

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-碳键形成对于药剂、天然产物和材料的合成已经变得极其重要。事实上，金属催化的交叉偶联反应和烯烃复分解现在是有机合成中最常用的反应之一。这些转化的重要性在很大程度上是由于它们广泛的官能团相容性以及大量且多样化的可作为起始材料的易于获得的化合物。 金属催化的 C-H 键活化随后形成碳-碳键也有可能在有机合成中变得异常强大。几种C-H活化过程，特别是那些由后过渡金属催化的过程，具有高度的官能团相容性。此外，由于几乎所有有机化合物都含有 C-H 键，因此起始材料的可用性无法超越。然而，绝大多数有机化合物含有多个 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能够选择性活化 C-H，而且能够形成随后的碳-碳键。该提案描述了旨在实现这些目标的强大催化方法的开发和应用。拟议的研究可分为三个具体目标。 将开发三类合成方法：（1）芳香亚胺的分子内邻位烷基化，（2）氮杂环的烷基化，（3）氮杂环的酰化。将确定每种方法的底物范围，并在适当的情况下开发对映选择性催化方法。每种方法的重要性也将通过药理活性剂的合成来证明。