Carbon-Hydrogen Bond Functionalization By Transition Metal Complexes

过渡金属配合物的碳氢键功能化

• 批准号: 7437237
• 负责人: Olafs Daugulis
• 金额: $ 24.77万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-05 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7437237
• 关键词: 2-amino-1-butanol; Alkylation; Amines; Amino Acids; Biological; Carbon; Chemistry; Complement; Condition; Coupling; Development; Generations; Goals; Halogens; Hydrocarbons; Hydrogen Bonding; Investigation; Lead; Mediating; Methodology; Methods; Object Attachment; Palladium; Pharmacologic Substance; Price; Process; Reaction; Reporting; Research; Route; Testing; Transition Elements; base; chelation; improved; interest; metal complex

DESCRIPTION (provided by applicant): The primary goal of the proposed research is to develop new and useful transformations using electrophilic carbon-hydrogen bond activation reactions mediated by transition metal complexes. Extensive synthetic methodology has been developed based on oxidative addition reactions of C-X bonds (X=halogen, heteroatom). Catalytic C-C bond forming reactions arising from C-H bond activations are less common despite the wider availability, price, and environmental advantages of the starting hydrocarbons compared to functionalized compounds. The reactions arising from C-H bond activation will complement the current methods for C-C bond formation and have a substantial impact on synthetic methodology. In this project, palladium-catalyzed coupling of C-H bonds with C-X bonds will be investigated leading to new and general methods for C-C bond formation. Preliminary studies suggest that the proposed chemistry is viable and will yield unique reactions useful in the synthesis of compounds of medicinal and biological interest. We have already achieved the first general palladium-catalyzed C-H activation/C-C coupling sequences at unactivated sp3 centers. The specific aims of the research are as follows: A. Expansion of the C-H activation/C-C bond formation method generality and convenience. A general method for alkylation/arylation/alkenylation of directing group containing arenes will be developed. Both ortho- and meta, para selectivity in these reactions should be accessible depending on the reaction conditions as described in Preliminary results section. A method for the arylation of unfunctionalized arenes will be developed. New auxiliaries for the arylation of sp3 C-H bonds will be investigated. B. Development of diastereoselective reactions. By using chiral auxiliaries, diastereoselective C-H bond arylations and alkylations will be achieved. This methodology will be tested in the synthesis of pharmaceutically relevant compounds. C. Mechanistic investigations. Mechanistic understanding should allow us to rationally improve the methodology developed during the preliminary studies, and to develop improved second-generation processes. The new methodologies developed in this research will lead to more efficient routes to Pharmaceuticals and their precursors. Substantial shortening of the reported routes to pharmaceutically relevant compounds are proposed.

描述（由申请人提供）：拟议研究的主要目标是使用通过过渡金属复合物介导的亲电碳 - 氢键激活反应来开发新的和有用的转换。广泛的合成方法是基于C-X键的氧化添加反应（X =卤素，杂原子）开发的。尽管与功能化化合物相比，催化C-C键形成由C-H键激活引起的反应较不常见。 C-H键激活引起的反应将补充当前的C-C键形成方法，并对合成方法产生重大影响。在该项目中，将研究C-H键与C-X键的钯催化耦合，从而导致C-C键形成的新的和一般的一般方法。初步研究表明，所提出的化学是可行的，将产生独特的反应，可用于合成药物和生物学意义的化合物。我们已经在未激活的SP3中心达到了第一个普通钯催化的C-C激活/C-C耦合序列。该研究的具体目的如下：A。C-H激活/C-C键形成方法的一般性和便利性的扩展。将开发一种含有指导组的烷基化/芳基化/烷基化的一般方法。正常和meta，这些反应中的Para选择性均应根据初步结果部分所述的反应条件来访问。将开发一种涉及不官能化领域的方法。将研究用于涉及SP3 C-H键的新辅助机。 B.非对映选择反应的发展。通过使用手性辅助机，将实现非映选择性C-H键芳基化和烷基化。该方法将在合成药物相关化合物的合成中进行测试。 C.机械调查。机械理解应该使我们能够合理地改善在初步研究期间开发的方法，并开发改进的第二代过程。这项研究中开发的新方法将导致通往药品及其前体的更有效的途径。提出了大量缩短报告的药物相关化合物的途径。