Exploiting Boron-Boron Exchange: Boron-catalysed C-H Borylation

利用硼-硼交换：硼催化的 C-H 硼化反应

• 批准号: NE/T014695/1
• 负责人: Stephen Thomas
• 金额: $ 0.91万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FT014695%2F1
• 关键词: Exploiting; Boron; Exchange; catalysed; Borylation

EPSRC : Andrew Bage : EPSRC/3202/R83279The pharmaceutical and agrochemical industries are dependent upon the construction of novel molecular structures to target new medicines and agrochemicals. One of the most generally applied and used methods to do this uses arylboronic esters building blocks. Therefore an extensive library of arylboronic esters is needed and the easy ability to continually increase this library is essential. The greater the library, the greater the potential for novel chemical structures. Arylboronic esters are currently prepared by a two-step process which is inherently wasteful and practically challenging. The direct production of arylboronic esters by C-H borylation is far more economic and has the potential to become a staple reaction, particularly for the medicinal chemistry and agrochemical industries. Currently, rare, toxic metals, typically iridium and rhodium, are used as catalysts for the C-H borylation reaction, but the reactions suffer from limited selectivity. This project will introduce broad-scope and selective boron-based catalysts for C-H borylation to give arylboronic esters. A boron-based catalyst would offer orthogonal reactivity and remove the need for exhaustive catalyst removal, as boron is far less toxic than the heavy metals currently used.The Fontaine group is the world leader in boron-based C-H borylation reactions. They have developed a series of stoichiometric and substoichiometric boron species that are capable of activating aryl C-H bonds to further reaction. The Thomas group has shown stoichiometric boron species can be transformed into catalysts by utilising the 'boron-boron exchange' mechanism. This mechanism shows impressive versatility and is vital to catalyst regeneration. Boron-boron exchange has been used to prepare alkyl- and alkenylboronic ester products and it will be applied to arene C-H borylation in this project. Initially, stoichiometric C-H borylation will be used to probe the efficacy of the boron-boron exchange mechanism for C-H borylation. This will include isolating reaction intermediates and directly observing exchange and catalyst regeneration. Subsequently, we will develop catalytic reactions using the fundamental knowledge gained. Optimisation will focus on functional group tolerance and the targeting of arylboronic esters of significant interest to the pharmaceutical and agrochemical industries. Ultimately, this project will showcase boron-boron exchange as a versatile tool for developing industrially-relevant building blocks and give a system that will rival current industrial methods for C-H borylation.

EPSRC：Andrew Bage：EPSRC/3202/R83279药物和农业化学行业取决于构建新型分子结构以靶向新药物和农业化学物质。使用Arylboronic Ester的构建块是最常用和使用的方法之一。因此，需要大量的芳基酯库，并且不断增加该库的易于使用的能力至关重要。文库越大，新型化学结构的潜力就越大。目前，芳基硼酯是通过两步过程来制备的，该过程本质上是浪费且实际上具有挑战性的。通过C-H Borylation直接生产芳基酯酯的经济性要大得多，并且有可能成为主食反应，尤其是对于药物化学和农业化学行业而言。当前，稀有的有毒金属（通常是虹膜和菱形）被用作C-H Borylation反应的催化剂，但反应的选择性有限。该项目将介绍用于C-H Borylation的宽阔和选择性的基于硼的催化剂，以提供芳基酯酯。基于硼的催化剂将提供正交的反应性，并消除清除详细催化剂的需求，因为硼的毒性远低于当前使用的重金属的毒性。Fontaine组是基于硼的C-H Borylation Reactions的世界领导者。他们已经开发了一系列化学计量和化学计量的硼，它们能够激活芳基C-H键以进一步反应。托马斯组显示，可以通过使用“硼 - 硼交换”机制将化学计量硼种类转化为催化剂。该机制显示出令人印象深刻的多功能性，对于催化剂再生至关重要。硼 - 波龙交换已用于制备烷基和烷基烷基酯产品，并将其用于该项目中的Arene C-H Borylation。最初，化学计量计的C-H Borylation将用于探测硼 - 波隆交换机制对C-H Borylation的疗效。这将包括分离反应中间体以及直接观察交换和催化剂再生。随后，我们将使用获得的基本知识来发展催化反应。优化将集中于功能群的耐受性以及对药物和农业化学产业具有重大兴趣的芳基酯的靶向。最终，该项目将展示硼孔交易所作为开发与工业相关的构建块的多功能工具，并提供一个系统，该系统将与当前的C-H Borylation相媲美。