Electrophilic Boranes: Directed Hydroboration, Borylation, and Related Reactions

描述(申请人提供)：由于硼酸衍生物在过渡金属催化的C-C偶联反应中的广泛使用，有机硼化学在药物的大规模生产和实验室规模合成中越来越重要。尤其是钯或镍催化的Suzuki-Miyaura硼酸偶联反应，由于其出色的催化剂效率和与多种医药杂环环境的兼容性，正在彻底改变实验药物的制备方式。拟议的研究将使用新的硼活化程序来获得合成重要的硼酸盐。重点是将简单的路易斯碱-硼烷络合物转化为多功能的硼烷和硼酸衍生物。利用定向氢化方法制备了多种杂环硼酸环境，并将在最近开发的含有次级C-B键的硼酸的条件下确认这些中间体在钯催化下的偶联化学。胺定向硼氢化的具体应用将研究HIV1抑制剂Batzelladine F和Batzelladine K共有的吡咯烷亚基的立体控制和合成。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，并探索在二氢维甲酸合成中的应用。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反应。这项技术将应用于不适合替代方法的底物，并将研究机理与合成之间的界面，以提高硼试剂的反应活性，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的相关性很重要，因为硼酸偶联技术正在为药物和实验药物的大规模和实验室规模的合成带来革命性的变化。硼酸还可用作生物活性物质和碳水化合物传感器。杂环底物是药物的常用构件，衍生的有机硼结构是杂环组装和功能化最有用的工具之一。

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.