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

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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.