Directed Hydroboration and Related Reactions

定向硼氢化反应及相关反应

• 批准号: 7246534
• 负责人: EDWIN VEDEJS
• 金额: $ 25.51万
• 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 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7246534
• 关键词: Acetals; Address; Air; Alcohols; Alkenes; Alkynes; Amines; Benzofurans; Boranes; Boronic Acids; Carbon; Catalysis; Complex; Condition; Coupling; Development; Ethers; Ethyl Ether; Generations; Halogens; Imines; Indoles; Intermediate resistance; Ions; Lactams; Length; Methodology; Methods; Nitrogen; Object Attachment; Organic Synthesis; Oxygen; Palladium; Pharmacologic Substance; Potassium; Procedures; Pyrrolidines; Reaction; Reagent; Relative (related person); Research; Structure; System; Technology; Toxic effect; Variant; Water; base; benzofuran; boronic acid; concept; cyclic amine; desire; diene; improved; indole; indoline; interest; next generation; programs; pyrrolidine; stereochemistry; Acetals; Address; Air; Alcohols; Alkenes; Alkynes; Amines; Benzofurans; Boranes; Boronic Acids; Carbon; Catalysis; Complex; Condition; Coupling; Development; Ethers; Ethyl Ether; Generations; Halogens; Imines; Indoles; Intermediate resistance; Ions; Lactams; Length; Methodology; Methods; Nitrogen; Object Attachment; Organic Synthesis; Oxygen; Palladium; Pharmacologic Substance; Potassium; Procedures; Pyrrolidines; Reaction; Reagent; Relative (related person); Research; Structure; System; Technology; Toxic effect; Variant; Water; base; benzofuran; boronic acid; concept; cyclic amine; desire; diene; improved; indole; indoline; interest; next generation; programs; pyrrolidine; 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）：在水均值技术中，Hydroporation是独一无二的，用于可用选项的多功能性，用于将C-B键转换为C-H，C-O，C-O，C-N，C-Halogen和C-C-C键。由于铃木和硼酸衍生物的heck偶联反应的重要性迅速增长，最近对水变的兴趣最近引起了人们的兴趣。显然，在发现，开发和制造下一代药物的药物以及综合复杂的学术兴趣结构的情况下，有机丙达旦耦合技术的这些变化将在集中重要。因此，改进的对硼烷和硼酸立体控制或立体控制的方法是有机合成的关键挑战之一。 硼酸比许多有机金属具有优势，因为通常可以隔离试剂，在各种轻度条件下发生键形成的激活，中间体对水具有抵抗力和空气，毒性问题很小，并且对控制基于碱性替代的差异的水平差异，众所周知。但是，对于不饱和碳的替代程度几乎没有替代程度的烷烃（或炔烃）底物，可用的水合方法的发展尚未得到很好的开发。这些问题可以通过杂原基取代基在底物中的效应来解决，这将是要进行的研究的重点。使用稳定的胺硼烷复合物的亲电激活，已经证明了一种新的氮指导水燃概念。新方法涉及产生反应性的硼离子对中间体，这些中间体能够进行重新控制和立体控制。该过程将用于制备环状胺硼烷，并利用这些中间体使用钯催化来合成各种衍生物。还将研究无钯引入C-C，C-N，C-O和C-X键的方法。该过程允许胺定向的烷烃和炔烃的内部功能，并具有区域和立体控制。类似的概念将应用于氧指导的硼氢化液。 使用相同的原理已经证明了高度选择性的氧指导的水燃方法。该程序的主要目的是研究以太或酒精氧指导的水力学的立体化学。