Directed Hydroboration and Related Reactions

定向硼氢化反应及相关反应

• 批准号: 6821783
• 负责人: EDWIN VEDEJS
• 金额: $ 26.48万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6821783
• 关键词: alcohols; alkenes; alkynes; boranes; catalyst; chemical bond; chemical reaction; chemical substitution; chemical synthesis; cyclic amine; ethers; method development; organic chemicals; oxygen; palladium; stereochemistry

DESCRIPTION (provided by applicant): Hydroboration is unique among the hydrometallation technologies for the versatility of available options for stereospecific conversion of C-B bonds into C-H, C-O, C-N, C-halogen, and C-C bonds. There has been intense recent interest in hydroboration because of the rapidly growing importance of the Suzuki and Heck coupling reactions of boronic acid derivatives. It is clear that these variations of organopalladium coupling technology will be centrally important in the discovery, development, and manufacture of the next generation of pharmaceutical agents, and in the synthesis of complex structures of academic interest. Improved methodology for regiocontrolled or stereocontrolled access to boranes and boronic acids is therefore one of the key challenges for organic synthesis. Boronic acids have advantages over many organometallics in that the reagents can usually be isolated if desired, activation for bond formation occurs under a variety of mild conditions, the intermediates are resistant to water and air, toxicity problems are minimal, and much is known about controlling the regiochemistry of hydroboration based on differences in degree of alkene substitution. However, available hydroboration methodology is not well developed for alkene (or alkyne) substrates where there is little, or no difference in degree of substitution at the unsaturated carbons. Such problems can be addressed by heteroatom substituent directing effects in the substrate, and that will be the focus of the research to be performed. A new concept for nitrogen-directed hydroboration has been demonstrated using electrophilic activation of stable amine borane complexes. The new method involves generation of reactive borenium ion pair intermediates that are capable of regiocontrolled and stereocontrolled hydroboration. The procedure will be used to prepare cyclic amine boranes and to exploit these intermediates for synthesis of a variety of derivatives using palladium catalysis. Methodology for palladium-free introduction of C-C, C-N, C-O and C-X bonds will also be studied. The procedure allows amine-directed internal functionalization of alkenes and alkynes with regio-and stereocontrol. A similar concept will be applied to oxygen-directed borenium hydroboration. Highly selective oxygen-directed hydroboration methodology has been demonstrated using the same principles. A major thrust of the program will be to investigate the stereochemistry of hydroborations directed by ether or alcohol oxygen.

描述（由申请人提供）：硼氢化在氢化金属技术中是独特的，因为C-B键立体定向转化为C-H、C-O、C-N、C-卤素和C-C键的可用选项的多功能性。由于硼酸衍生物的Suzuki和Heck偶联反应的重要性迅速增长，最近对硼氢化反应产生了强烈的兴趣。很明显，有机钯偶联技术的这些变化将是非常重要的发现，开发和制造的下一代药剂，并在合成复杂的结构的学术兴趣。因此，改进区域控制或立体控制获得硼烷和硼酸的方法是有机合成的关键挑战之一。 硼酸具有优于许多有机金属化合物的优点，因为如果需要，试剂通常可以分离，在各种温和条件下发生键形成的活化，中间体耐水和空气，毒性问题最小，并且关于基于烯烃取代度的差异控制硼氢化的区域化学已知很多。然而，可用的硼氢化方法对于烯烃（或炔）底物没有很好的开发，其中在不饱和碳上的取代度几乎没有差异或没有差异。这些问题可以通过基质中的杂原子取代基导向效应来解决，这将是将要进行的研究的焦点。利用稳定的胺硼烷络合物的亲电活化，证明了氮导向硼氢化的新概念。该新方法涉及生成能够进行区域控制和立体控制的硼氢化的反应性borenium离子对中间体。该程序将被用来制备环胺硼烷，并利用这些中间体合成的各种衍生物使用钯催化。还将研究无钯引入C-C、C-N、C-O和C-X键的方法。该方法允许胺导向的烯烃和炔的区域和立体控制的内部官能化。类似的概念将应用于氧导向的硼氢化反应。 使用相同的原理已经证明了高选择性的氧导向硼氢化方法。该计划的一个主要目标是研究由醚或醇氧指导的硼氢化的立体化学。