Electrophilic Boranes: Directed Hydroboration, Borylation, and Related Reactions

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偶联中的广泛使用，有机硼化学在药物的大规模生产以及实验室规模合成中越来越重要。特别地，钯或镍催化的硼酸的Suzuki-Miyaura偶联由于其优异的催化剂效率和与许多医学感兴趣的杂环环境的相容性而彻底改变了实验药物的制备方式。拟议的研究将使用硼活化的新程序来获得合成上重要的硼酸盐。重点是简单的刘易斯碱-硼烷复合物转化为多功能硼烷和硼酸衍生物。各种杂环硼酸环境将使用定向硼氢化方法制备，并且这些中间体的钯催化偶联化学将在最近开发的含有仲C-B键的硼酸条件下得到证实。胺定向硼氢化的具体应用将研究立体控制和合成HIV 1抑制剂batzelladine F和batzelladine K共有的吡咯烷亚基。新开发的胺和亚磷酸酯硼烷的N-定向离子氢化将用于控制相对和绝对立体化学，并探索应用于二氢视黄酸合成。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硼化。该技术将应用于替代方法不适合的基底，并将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。 公共卫生相关性：获得新的有机硼环境很重要，因为硼酸偶联技术正在使大规模以及实验室规模的药物和实验药物合成发生革命性变化。硼酸作为生物活性剂和作为碳水化合物传感器也是令人感兴趣的。杂环底物是药物的常用结构单元，衍生的有机硼结构是杂环组装和功能化的最有用的工具之一。

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.