Novel Organoboron Chemistry Utilizing Tetrahydroxydiborane

利用四羟基乙硼烷的新型有机硼化学

• 批准号: 8516052
• 负责人: GARY A MOLANDER
• 金额: $ 32.65万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-07 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8516052
• 关键词: Acids; Address; Alkylating Agents; Anions; Boron; Boronic Acids; Carbon; Chemicals; Chemistry; Complex; Coupled; Coupling; Crystallization; Dependency; Development; Drug Industry; Esters; Future; Goals; Hydrolysis; Industry; Marketing; Methods; Molecular; Nitrogen; Organic Synthesis; Oxygen; Pattern; Pharmacologic Substance; Procedures; Process; Production; Productivity; Protocols documentation; Reaction; Reagent; Research; Route; Solutions; Techniques; Time; Transition Elements; base; bis(pinacolato)diboron; catalyst; chemical reaction; cost; cost effective; design; drug development; drug discovery; functional group; novel; novel strategies; programs; protocol development; small molecule; sound; wasting

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.

描述（由申请人提供）：拟议研究的目标是通过开发新试剂并随后利用这些试剂的新型反应模式来促进有机分子的构建。本文描述了用于有机硼化合物的新合成的方案，其将提高化学家在有机分子合成中的生产率和效率。四羟基二硼烷[（HO）2B-B（OH）2]及其商业合成前体（Me 2N）2B-B（NMe 2）2的开发将减少对完全无效的双（频哪醇合）二硼（B2 pin 2）的依赖。提出了独特、更具成本效益且环保的合成硼酸和多种衍生物的方法。最重要的是，将开发化学反应性的新前景。的结果 所描述的研究将实现将硼引入有机分子的新方法;比以前的方法更可持续的方法。直接获得硼酸将使这些方案在两个重要方面更加通用：1）需要反应性但不稳定的硼酸的顺序反应可以在没有繁琐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。这不仅解决了通常采用的多步方案固有的显著效率，而且还将合成方法扩展到新型有机硼以及在常规处理期间易于通过原脱硼化而显著降解的那些硼酸。2)可以直接合成各种更有用和稳健的有机三氟硼酸酯，而不需要使用频哪醇硼酸酯的方案所需的浪费的水解方法。 利用bisbora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的新方法代表了所述研究的另一个核心。这些协议将使新的有机硼试剂的形成在一个直接的方法。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，包括亲核性聚合试剂、多氟烷基三氟硼酸酯和<$-三氟硼酸根取代的氮和氧杂环的接合，这将为有机合成中的长期挑战提供解决方案。 使用开发的新方法，一些独特的2-烷基化试剂，包括氨基烷基化和烷氧基烷基化试剂，将以对映体纯的形式合成，并将开发基于与嵌入的官能团的次级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和插入立体中心与完整的立体化学保真度到有机基板通过交叉耦合。