Novel Organoboron Chemistry Utilizing Tetrahydroxydiborane

描述(由申请人提供)：提出的研究目标是通过开发新的试剂并随后开发这些试剂的新的反应模式来促进有机分子的构建。这里描述了用于有机硼化合物的新合成的方案，该方案将提高化学家在合成有机分子中的生产率和效率。四羟基二硼烷[(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无效的双(Pinacoloato)二硼(B2pin2)的依赖。提出了独特的、更具成本效益的、对环境无害的合成硼酸和各种衍生物的方法。最重要的是，将开发化学反应的新前景。由于…… 上述研究将实现将硼引入有机分子的新方法；这一过程比以前的方法更可持续。直接获得硼酸将在两个重要方面使这些协议更加通用：1)需要活性但不稳定的硼酸的顺序反应可以在没有冗长和低效的水解过程的情况下进行，从而允许快速和更可持续地获得高附加值产品。这不仅将解决通常采用的多步方案所固有的显著效率问题，而且还将把合成方法扩展到新的有机硼以及那些在常规处理过程中容易因协议脱碳而显著降解的硼酸。2)可以直接合成各种更有用和更坚固的有机三氟硼酸盐，而不需要使用频碳硼酸盐的协议所需的浪费的水解方法。有机硼化合物的新方法，利用了双硼化合物的类似硼阴离子的反应模式，避免了昂贵的过渡金属催化剂，是所描述的研究的另一个中心。这些方案将使以直接方法形成新型有机硼试剂成为可能。重要的是，这些有用的新试剂将被用于前所未有的成键反应，包括亲核试剂、多氟烷基三氟硼酸盐和三氟硼氮氧杂环化合物的参与，这将为有机合成中长期存在的挑战提供解决方案。利用开发的新方法，将以对映体的形式合成许多独特的2‘烷基化试剂，包括氨基烷基化和烷氧基烷基化试剂，并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。这些独特的试剂将允许前所未有的键结构，并通过交叉偶联将立体中心完全立体地插入到有机底物中。

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.