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: 7623529
• 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/7623529
• 关键词: 2-amino-1-butanol; Alkylation; Amines; Amino Acids; Biological; Carbon; Chemistry; Complement; Coupling; Development; Generations; Goals; Halogens; Hydrocarbons; Hydrogen Bonding; Investigation; Lead; Mediating; Methodology; Methods; 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）：所提议研究的主要目标是利用过渡金属配合物介导的亲电碳氢键活化反应来开发新的有用的转化。基于 C-X 键（X=卤素、杂原子）的氧化加成反应，已经开发出广泛的合成方法。尽管与官能化化合物相比，起始碳氢化合物具有更广泛的可用性、价格和环境优势，但由 C-H 键活化引起的催化 C-C 键形成反应不太常见。 C-H键活化产生的反应将补充目前的C-C键形成方法，并对合成方法产生重大影响。在该项目中，将研究钯催化的 C-H 键与 C-X 键的偶联，从而形成 C-C 键形成的新的通用方法。初步研究表明，所提出的化学方法是可行的，并将产生可用于合成具有医学和生物学意义的化合物的独特反应。我们已经在未激活的 sp3 中心实现了第一个通用钯催化的 C-H 激活/C-C 偶联序列。研究具体目的如下： A.扩展C-H活化/C-C键形成方法的通用性和便利性。将开发一种用于含导向基团的芳烃的烷基化/芳基化/烯基化的通用方法。这些反应中的邻位、间位、对位选择性应该是可实现的，具体取决于初步结果部分中所述的反应条件。将开发一种未官能化芳烃的芳基化方法。将研究用于 sp3 C-H 键芳基化的新助剂。 B.非对映选择性反应的发展。通过使用手性助剂，将实现非对映选择性C-H键芳基化和烷基化。该方法将在药物相关化合物的合成中进行测试。 C. 机制研究。机理的理解应该使我们能够合理地改进在初步研究中开发的方法，并开发改进的第二代工艺。这项研究中开发的新方法将为药物及其前体提供更有效的途径。建议大幅缩短已报道的药学相关化合物的路线。