Directed Hydroboration and Related Reactions

定向硼氢化反应及相关反应

• 批准号: 7082790
• 负责人: EDWIN VEDEJS
• 金额: $ 26.27万
• 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/7082790
• 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.

说明(申请人提供)：在湿法金属化法技术中，硼氢化是独一无二的，可用于将C-B键立体定向转化为C-H、C-O、C-N、C-卤素和C-C键。近年来，由于硼酸衍生物的Suzuki和Heck偶联反应的重要性迅速增长，人们对氢化硼化反应产生了浓厚的兴趣。显然，这些变化的有机钯偶联技术将在发现、开发和制造下一代药物制剂以及合成具有学术意义的复杂结构方面发挥核心作用。因此，改进区域控制或立体控制获取硼烷和硼酸的方法是有机合成的关键挑战之一。 与许多有机金属相比，硼酸具有以下优势：如果需要，通常可以分离试剂，在各种温和的条件下进行键形成的活化，中间体对水和空气的耐受性，毒性问题最小，以及基于烯烃取代程度的差异来控制氢化硼化的区域化学。然而，对于不饱和碳取代度很小或没有差异的烯烃(或炔烃)底物，现有的氢化硼化方法并未得到很好的开发。这些问题可以通过杂原子在底物中的取代基导向效应来解决，这将是未来研究的重点。通过稳定的胺-硼烷络合物的亲电活化，证明了氮直接氢化硼的新概念。新方法包括生成反应性的硼离子对中间体，这些中间体能够进行区域控制和立体控制的氢化反应。该方法将用于制备环胺硼烷，并利用这些中间体在钯催化下合成各种衍生物。还将研究无钯引入C-C、C-N、C-O和C-X键的方法。该程序允许在区域和立体控制下对烯和炔进行胺导向的内部官能化。类似的概念也将应用于氧直接的硼氢化反应。 使用同样的原理，已经证明了高选择性的氧直接氢化硼方法。该计划的主要目的将是研究乙醚或醇氧引导的硼氢化反应的立体化学。