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: 6999333
• 负责人: JONATHAN A ELLMAN
• 金额: $ 31.29万
• 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/6999333
• 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-碳键形成对于药物制剂、天然产物和材料的合成已经变得非常重要。事实上，金属催化的交叉偶联反应和烯烃复分解反应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，以及大量不同的可用作起始材料的易得化合物。 金属催化的C-H键活化，然后形成碳-碳键，也有可能在有机合成中变得非常强大。一些C-H活化过程，特别是由后过渡金属催化的那些，是高度官能团相容的。此外，由于几乎每种有机化合物都含有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键活化对于开发有用的合成方法至关重要。此外，必须确定不仅能够选择性C-H活化，而且能够随后形成碳-碳键的催化剂。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。 本文主要介绍三种合成方法：（1）芳香亚胺的分子内邻位烷基化，（2）含氮杂环的烷基化，（3）含氮杂环的酰化。将确定每种方法的底物范围，并在适当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合成抗肿瘤活性剂来证明。