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 制药和农用化学品行业依赖于构建新的分子结构来靶向新药物和农用化学品。最普遍应用和使用的方法之一是使用芳基硼酸酯结构单元。因此，需要一个广泛的芳基硼酸酯库，并且能够轻松地持续增加该库是至关重要的。库越大，新化学结构的潜力就越大。目前芳基硼酸酯是通过两步法制备的，该方法本质上是浪费的并且在实践中具有挑战性。通过 C-H 硼基化直接生产芳基硼酯更加经济，并且有可能成为主要反应，特别是对于药物化学和农化行业。目前，稀有有毒金属（通常是铱和铑）被用作 C-H 硼基化反应的催化剂，但该反应的选择性有限。该项目将引入广泛且选择性的硼基催化剂，用于 C-H 硼基化，生成芳基硼酸酯。硼基催化剂将提供正交反应性，并且无需彻底去除催化剂，因为硼的毒性远低于目前使用的重金属。Fontaine 集团是硼基 C-H 硼化反应的世界领先者。他们开发了一系列化学计量和亚化学计量的硼物质，能够激活芳基 C-H 键以进一步反应。托马斯小组已经证明，通过利用“硼-硼交换”机制，化学计量的硼物质可以转化为催化剂。该机制显示出令人印象深刻的多功能性，对催化剂再生至关重要。硼-硼交换已用于制备烷基硼酸酯和烯基硼酸酯产品，本项目将应用于芳烃C-H硼化反应。最初，化学计量的 C-H 硼化作用将用于探讨硼-硼交换机制对 C-H 硼化作用的功效。这将包括分离反应中间体并直接观察交换和催化剂再生。随后，我们将利用所获得的基础知识来开发催化反应。优化将侧重于官能团耐受性以及对制药和农化行业具有重要意义的芳基硼酸酯的靶向。最终，该项目将展示硼-硼交换作为开发工业相关构建模块的多功能工具，并提供一个可与当前 C-H 硼化工业方法相媲美的系统。