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

制药和农用化学工业依赖于新型分子结构的构建来靶向新药和农用化学品。最常用的方法之一是使用芳基硼酯构建块。因此，需要一个广泛的芳基硼酯库，并且易于不断增加这个库是必不可少的。文库越大，发现新化学结构的潜力就越大。芳香硼酯目前是由两步法制备的，这本身就是浪费和实践上的挑战。通过C-H硼化反应直接生产芳基硼酯要经济得多，并且有可能成为一种主要反应，特别是在药物化学和农化工业中。目前，稀有的有毒金属，特别是铱和铑，被用作C-H硼化反应的催化剂，但这些反应的选择性有限。本项目将介绍广泛、选择性的硼基催化剂，用于C-H硼化反应生成芳基硼酯。硼基催化剂将提供正交反应性，并且不需要彻底去除催化剂，因为硼的毒性远低于目前使用的重金属。Fontaine集团是世界上以硼为基础的C-H硼化反应的领导者。他们已经开发了一系列化学计量和亚化学计量的硼物质，这些物质能够激活芳基C-H键以进一步反应。托马斯小组已经证明，化学计量硼可以通过利用“硼-硼交换”机制转化为催化剂。该机制显示了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和烯基硼酯产品，本项目将应用于芳烃C-H硼化反应。首先，化学计量学C-H硼化将用于探索硼-硼交换机制对C-H硼化的有效性。这将包括分离反应中间体和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开发催化反应。优化将集中在功能群的耐受性和靶向芳基硼酯对制药和农化工业的重大利益。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通用工具，并提供一种可与当前工业方法相媲美的C-H硼化系统。

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.