Transition-metal-free reactions of organoboranes.

有机硼烷的无过渡金属反应。

• 批准号: RGPIN-2014-05279
• 负责人: Bolshan, Yuri
• 金额: $ 2.33万
• 依托单位: University of Ontario Institute of Technology
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=588317
• 关键词: Transition; metal; free; reactions; organoboranes.

The aim of my research program is to develop novel transition-metal-free carbon-carbon (C-C) bond forming methodologies using organoboranes. The underlying theme of my proposal is an amphoteric reactivity of organoboranes. Boranes are electrophilic when neutral but nucleophilic when negatively charged. In situ generation of nucleophilic species from neutral boranes and their novel reactions are being discussed. C-C bond forming reactions involving organoboron compounds are usually associated with transition-metals that are expensive, toxic and often require the presence of sophisticated ligands. Boron is inexpensive and environmentally benign. Moreover, its low toxicity resulted in the incorporation of boron into pharmaceuticals. Proposed reactions provide “greener” alternative to the currently available protocols. The first section focuses on the development of novel C-C bond forming reactions using potassium organotrifluoroborate salts. Recently, we have discovered a single-step synthesis of ketones from acyl chlorides and trifluoroborates. We propose that in situ generated electrophilic difluoroborane interacts with a carbonyl functionality of the acyl chloride producing nucleophilic borates and electrophilic species. The reaction between newly formed nucleophilic borate and an electrophile affords propargyl ketones. Importantly, the reaction occurs in the absence of transition metals. Similarly, reactions of imines, isocyanates and aldehydes with trifluoroborates under the developed conditions are anticipated to form important functionalities such as amines, amides and alcohols respectively. The second section describes the opening of aziridinium ion with organoboronic acids and the application of the reaction to the synthesis of beta and gamma amino acids. To our knowledge, there are no literature examples of aziridinium ions reacting with organoborones. In this case, neutral boronic acids will be activated and directed to the aziridinium electrophilic center by the Lewis basic moiety present in the substrate. The establishment of stereocenters, which takes place at the early stage of the synthesis, relies on well-known epoxidation protocols. Subsequent reactions are stereospecific, which prevents epimerization of the chiral centers. Therefore, the enantiomeric purity of the starting epoxide will be translated to the final amino acid. The final section of my proposal focuses on the development of transition-metal-free reactions between gaseous carbon monoxide and organoboranes. This approach describes novel reactions based on the activation of neutral organoboranes with carbon monoxide. I propose efficient synthesis of acyl boronate esters and complex trifluroborates that are known to have great synthetic potential but difficult to prepare. In addition, novel bora-Brook rearrangements of acyl boronates are being described. Overall, outcomes of this research program will result in greater atom economy and will decrease the amount of toxic waste associated with metals in both academic and industrial settings. In addition, novel methodologies will ensure rapid access to diverse chiral molecules, which is crucial for the development of complex molecules and natural products. In summary, the proposed research program will have a significant impact on our understanding of the fundamental aspects of boron chemistry, which in turn will lead to the development of green reactions for the synthesis of compounds of biological and medicinal relevance. This program will serve as an excellent tool for the training of both graduate and undergraduate students.

我的研究计划的目的是开发新的过渡金属的碳-碳（C-C）键形成方法使用有机硼烷。我的提议的基本主题是有机硼烷的两性反应性。硼烷在中性时是亲电的，但在带负电时是亲核的。讨论了中性硼烷原位生成亲核物种及其新反应。涉及有机硼化合物的C-C键形成反应通常与过渡金属有关，过渡金属昂贵、有毒并且通常需要复杂配体的存在。硼价格低廉，对环境无害。此外，其低毒性导致硼被掺入药物中。提出的反应提供了“绿色”替代目前可用的协议。 第一部分主要介绍了有机三氟硼酸钾在新型C-C键形成反应中的应用。最近，我们发现了由酰氯和三氟硼酸盐一步合成酮的方法。我们建议，在原位产生的亲电二氟硼烷与酰氯产生亲核硼酸盐和亲电物种的羰基官能团相互作用。新形成的亲核硼酸盐和亲电试剂之间的反应提供炔丙基酮。重要的是，该反应在不存在过渡金属的情况下发生。类似地，亚胺、异氰酸酯和醛与三氟硼酸盐在所开发的条件下的反应预计分别形成重要的官能团，例如胺、酰胺和醇。 第二部分描述了氮丙啶鎓离子与有机硼酸的开环反应以及该反应在合成β和γ氨基酸中的应用。据我们所知，没有文献中氮丙啶鎓离子与有机硼反应的例子。在这种情况下，中性硼酸将被活化并通过基底中存在的刘易斯碱性部分引导至氮丙啶鎓亲电中心。在合成的早期阶段发生的立构中心的建立依赖于众所周知的环氧化方案。随后的反应是立体特异性的，这防止了手性中心的差向异构化。因此，起始环氧化物的对映体纯度将转化为最终氨基酸。 我的建议的最后一部分集中在气态一氧化碳和有机硼烷之间的过渡金属自由反应的发展。该方法描述了基于中性有机硼烷与一氧化碳的活化的新反应。我建议有效合成酰基硼酸酯和复杂的三氟硼酸酯，已知具有很大的合成潜力，但难以制备。此外，新的bora-Brook重排的酰基硼酸酯被描述。 总的来说，这项研究计划的成果将导致更大的原子经济，并将减少学术和工业环境中与金属相关的有毒废物的数量。此外，新的方法将确保快速获得不同的手性分子，这对于复杂分子和天然产物的开发至关重要。总之，拟议的研究计划将有显着的影响，我们了解硼化学的基本方面，这反过来又会导致绿色反应的发展，用于合成化合物的生物和医药相关性。该计划将作为研究生和本科生培训的一个很好的工具。