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: 7651662
• 负责人: EDWIN VEDEJS
• 金额: $ 31.11万
• 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/7651662
• 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）：由于硼酸衍生物在过渡金属催化的C-C偶联中的广泛应用，有机硼化学在大规模生产和实验室规模的药物合成中越来越重要。特别是钯或镍催化的硼酸铃木-宫浦偶联，由于其优异的催化剂效率和与许多具有药用价值的杂环环境的相容性，正在彻底改变实验性药物的制造方式。拟议的研究将使用硼活化的新程序获得合成重要的硼酸盐。重点是简单的路易斯碱硼烷配合物转化为多功能硼烷和硼酸衍生物。利用定向硼氢化方法制备了各种杂环硼酸环境，并在最近开发的含有二级C-B键的硼酸条件下确认了钯催化这些中间体的偶联化学。胺定向硼氢化的具体应用将研究立体控制和合成与hiv抑制剂巴齐拉定F和巴齐拉定k共同的吡罗烷亚基。新开发的胺和亚磷酸盐硼烷的n定向离子氢化将用于控制相对和绝对立体化学，并探索在二氢类维甲酸合成中的应用。新的胺硼烷活化方法也允许杂环底物的分子内和分子间亲电硼化。该技术将应用于其他方法不适合的底物，并研究机理与合成之间的界面，以提高硼试剂的反应性，并开发相关的有机铝试剂。