A Cycloaddition Protocol For the Synthesis of Functionalised Heteroaromatic Boronic Esters

在过去的十年里，精细化学品行业生产具有有效临床特征但在较短时间内的新型治疗药物的压力越来越大，这已经彻底改变了药物化学。特别是，结构活性关系（SAR）数据的采集，药物化学家设计新的潜在的生物活性分子的主要手段，已显着促进了高通量合成技术的出现。这种药物发现过程的一个关键要素是具有有用功能的起始化合物的可用性，以便进一步加工，从而可以对生物学和理化性质进行系统研究。在这种情况下，我们已经在实验室开展了一项研究计划，以开发芳香族和杂芳香族硼酸酯的新策略。这些化合物是现代有机化学中最有价值的合成中间体之一。它们在工业和学术界都有广泛的应用，主要是因为它们能够通过Pd催化的交叉偶联反应与各种芳族底物形成碳-碳键。尽管它们很受欢迎，但它们的合成可能相当艰巨，特别是如果人们希望产生复杂的类似物。为了解决这些限制，该提议提出使用容易获得的炔基硼酸酯的环加成反应来制备高度官能化的芳族和杂芳族硼酸酯。

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.