Electrophilic Boranes: Directed Hydroboration, Borylation, and Related Reactions

亲电硼烷：定向硼氢化、硼化和相关反应

• 批准号: 8067102
• 负责人: EDWIN VEDEJS
• 金额: $ 30.33万
• 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 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8067102
• 关键词: Acids; Alkenes; Aluminum; Amines; Boranes; Boron; Boronic Acids; Carbohydrates; Carbon; Chemistry; Complex; Coupling; Environment; HIV-1; Hydrogenation; Laboratories; Metals; Methodology; Methods; Nickel; Nitrogen; Oxygen; Palladium; Pharmaceutical Preparations; Pharmacologic Substance; Phosphites; Procedures; Pyrrolidines; Reaction; Reagent; Relative (related person); Structure; Techniques; Technology; Transition Elements; base; batzelladine F; catalyst; diene; improved; inhibitor/antagonist; interest; large scale production; public health relevance; pyrrolidine; sensor; stereochemistry; tool

DESCRIPTION (provided by applicant): Organoboron chemistry is increasingly important in large-scale production as well as laboratory-scale synthesis of pharmaceuticals due to the widespread use of boronic acid derivatives in transition metal- catalyzed C-C coupling. In particular, palladium or nickel catalyzed Suzuki-Miyaura coupling of boronic acids is revolutionizing the way that experimental drugs are made due to its excellent catalyst efficiency and compatibility with numerous heterocyclic environments of medicinal interest. The proposed studies will access synthetically important boronates using new procedures for boron activation. The emphasis is on conversion of simple Lewis base-borane complexes into versatile borane and boronic acid derivatives. A variety of heterocyclic boronic acid environments will be prepared using directed hydroboration methodology, and palladium catalyzed coupling chemistry of these intermediates will be confirmed under recently developed conditions for boronic acids that contain a secondary C-B bond. Specific applications of amine directed hydroboration will study stereocontrol and the synthesis of a pyrrolidine subunit common to the HIV1 inhibitor batzelladine F and batzelladine K. Newly developed N-directed ionic hydrogenations of amine and phosphite boranes will be used to control relative and absolute stereochemistry, and to explore applications to dihydroretinoid synthesis. The new amine borane activation methods also allow intramolecular and intermolecular electrophilic borylation of heterocyclic substrates. This technique will be applied to substrates where alternative methods are not suitable and the interface between mechanism and synthesis will be studied to improve the reactivity of boron reagents and to develop related organoaluminum reagents. PUBLIC HEALTH RELEVANCE: Relevance Access to new organoboron environments is important because boronic acid coupling technology is revolutionizing large-scale as well as lab-scale synthesis of pharmaceuticals and experimental drugs. Boronic acids are also of interest as biologically active agents, and as carbohydrate sensors. Heterocyclic substrates are common building blocks for pharmaceuticals, and the derived organoboron structures are among the most useful tools for heterocycle assembly and functionalization.

描述（由申请人提供）：有组织的化学在大规模生产以及实验室规模的合成中越来越重要，这是由于在过渡金属催化的C-C偶联中广泛使用硼酸衍生物而导致的药物。特别是，钯或镍催化的硼酸的铃木 - 锯齿耦合正在彻底改变实验药物的出色催化剂效率和与许多药用杂环环境的兼容，从而改变了实验性药物的方式。拟议的研究将使用新的硼激活程序访问合成重要的硼酸盐。重点是将简单的刘易斯基碱复合物转化为多功能硼烷和硼酸衍生物。将使用定向的液压方法来制备各种杂环硼酸环境，并将在最近开发的硼酸中含有次生C-B键的硼酸条件下确认这些中间体的钯催化的耦合化学。胺定向液压的特定应用将研究立体控制以及HIV1抑制剂Batzelladine F和Batzelladine K的吡咯烷亚基的合成。新开发的N指导的离子氢化将用于胺和磷酸硼烷的离子氢化，可用于控制相关和绝对配置，并探讨了构成的配置。新的胺硼烷活化方法还允许杂环底物的分子内和分子间亲电植物化。该技术将应用于不合适的替代方法的底物，并将研究机理和合成之间的界面以改善硼试剂的反应性并开发相关的有机铝剂试剂。 公共卫生相关性：与新有机体环境的相关性很重要，因为硼酸偶联技术正在彻底改变大规模的大规模以及实验室规模的制药和实验药物的合成。硼酸也作为生物活性剂和碳水化合物传感器感兴趣。杂环底物是药物的常见构件，衍生有机体结构是杂环组装和功能化的最有用的工具之一。