A Cycloaddition Protocol For the Synthesis of Functionalised Heteroaromatic Boronic Esters

精细化学品行业面临越来越大的压力，要求其在较短的时间内生产出具有有效临床特征的新型疗法，这在过去十年中使药物化学发生了革命性的变化。特别是，高通量合成技术的出现极大地促进了结构活性关系(SAR)数据的获取，这是药物化学家设计新的潜在生物活性分子的主要手段。这一药物发现过程的一个关键因素是提供具有有用功能的起始化合物以供进一步阐述，这样就可以对其生物和物理化学性质进行系统的研究。在此背景下，我们在实验室开展了一项研究计划，以开发一种新的策略来开发芳香族和杂芳族硼酸酯。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。它们广泛应用于工业和学术界，很大程度上是因为它们能够通过钯催化的交叉偶联反应在各种芳香族底物上形成碳-碳键。尽管它们很受欢迎，但它们的合成可能相当困难，特别是如果一个人希望产生复杂的类似物。为了解决这些限制，本提案提出了利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香族和杂芳族硼酸酯。

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.