Novel Organoboron Chemistry Utilizing Tetrahydroxydiborane

描述（由申请人提供）：所提出的研究目标是通过开发新试剂并随后利用这些试剂的新颖反应模式来促进有机分子的构建。本文描述了有机硼化合物的新颖合成方案，这将提高化学家在有机分子合成中的生产力和效率。四羟基乙硼烷 [(HO)2B-B(OH)2] 及其商业合成前体 (Me2N)2B-B(NMe2)2 的开发将减少对完全低效的双(频那醇)二硼 (B2pin2) 的依赖。提出了独特的、更具成本效益且对环境无害的合成硼酸和各种衍生物的程序。最重要的是，化学反应的新前景将会被开发出来。由于 通过所描述的研究，将实现将硼引入有机分子的新方法；比以前的方法更具可持续性的过程。直接获取硼酸将使这些方案在两个重要方面更加通用：1）不需要繁琐且低效的水解程序即可进行需要反应性但不稳定的硼酸的顺序反应，从而允许快速且更可持续地获得高附加值产品。这不仅可以提高通常采用的多步骤方案所固有的显着效率，而且还可以将合成方法扩展到新型有机硼以及那些在常规处理过程中容易因原​​脱硼而显着降解的硼酸。 2) 可以直接合成各种更有用和更稳定的有机三氟硼酸盐，而无需使用硼酸频那醇盐方案所需的浪费的水解方法。 利用双硼酸化合物的硼基阴离子样反应模式并避免昂贵的过渡金属催化剂的有机硼新方法代表了所述研究的另一个核心。这些方案将能够以直接方法形成新型有机硼试剂。重要的是，这些有用的新试剂将用于前所未有的成键反应，包括亲核反极性试剂、多氟烷基三氟硼酸盐和三氟硼酸取代的氮和氧杂环的参与，这将为有机合成中长期存在的挑战提供解决方案。 使用开发的新方法，将合成对映体纯形式的许多独特的2'烷基化试剂，包括氨基烷基化剂和烷氧基烷基化剂，并且将开发基于与嵌入官能团的二次相互作用的交叉偶联方案。这些独特的试剂将实现前所未有的键合构建，并通过交叉偶联将具有完全立体化学保真度的立体中心插入有机底物中。

DESCRIPTION (provided by applicant): The goal of the research proposed is to facilitate the construction of organic molecules by developing new reagents and subsequently exploiting the novel reactivity patterns of those reagents. Herein are described protocols for novel syntheses of organoboron compounds that will increase the productivity and efficiency of chemists in the synthesis of organic molecules. The development of tetrahydroxydiborane [(HO)2B-B(OH)2] and its commercial synthetic precursor, (Me2N)2B-B(NMe2)2, will reduce dependency on the wholly inefficient bis(pinacoloato)diboron (B2pin2). Proposed are unique, more cost effective, and environmentally sound procedures for the synthesis of boronic acids and diverse derivatives. Most importantly, new vistas for chemical reactivity will be developed. As a result of the studies described, novel methods for the introduction of boron into organic molecules will be realized; processes that are far more sustainable than previous methods. Direct access to boronic acids will make these protocols more versatile in two important ways: 1) Sequential reactions that require reactive but unstable boronic acids can be carried out without a tedious and inefficient hydrolysis procedure, thus permitting rapid and more sustainable access to high value-added products. Not only would this address significant efficiencies inherent to the multi-step protocol generally employed, but it would also extend synthetic methods both to novel organoborons as well as those boronic acids that are prone to significant degradation by protodeboronation during routine handling. 2) A variety of more useful and robust organotrifluoroborates can be directly synthesized without the wasteful hydrolysis methods required with protocols employing pinacolboronates. Novel approaches to organoborons that take advantage of boryl anion-like reactivity patterns of bisbora compounds and avoid expensive transition metal catalysts represent another centerpiece of the described research. These protocols will enable the formation of novel organoboron reagents in a direct approach. Importantly, these useful new reagents will be employed in unprecedented bond-forming reactions, including the engagement of nucleophilic umpolung reagents, polyfluoroalkyltrifluoroborates, and ¿-trifluoroborato- substituted nitrogen- and oxygen heterocycles that will provide solutions to long-standing challenges in organic synthesis. Using the novel methods developed, a number of unique 2¿ alkylating reagents, including amino alkylating and alkoxy alkylating agents, will be synthesized in enantiopure form, and protocols for their cross-coupling, based on secondary interactions with embedded functional groups, will be developed. These distinctive reagents will allow unprecedented bond constructions and insertion of stereocenters with complete stereochemical fidelity into organic substrates via cross-coupling.