A Cycloaddition Protocol For the Synthesis of Functionalised Heteroaromatic Boronic Esters

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Increasing pressure on the Fine Chemicals Industry to produce novel therapeutics with an efficacious clinical profile but within a shorter timeframe has revolutionised medicinal chemistry over the last decade. In particular, the acquisition of structure activity relationships (SAR) data, the primary means by which medicinal chemists design new potential bioactive molecules, has been significantly promoted by the advent of high throughput synthesis techniques. A key element of this drug discovery process is the availability of starting compounds that bear useful functionality for further elaboration, such that a systematic investigation of the biological and physiochemical properties can be made. In this context, we have embarked upon a programme of research in our labs to develop a new strategy to aromatic and heteroaromatic boronic esters. These compounds are amongst the most valuable synthetic intermediates in modern organic chemistry. They are used throughout both industry and academia, largely because of their ability to form carbon-carbon bonds to various aromatic substrates through a Pd-catalysed cross-coupling reaction. Despite their popularity, their synthesis can be rather arduous, especially if one wishes to generate complex analogues. In an effort to address these limitations, this proposal sets out to use cycloaddition reactions of readily available alkynylboronates to prepare highly functionalised aromatic and heteroaromatic boronic esters.