Nucleophilic Alkaline Earth Boryls: From Conception and Theory to Application

现代化学合成方法为人类健康和福祉提供了一些最大的好处。硼化合物提供了化学中最广泛使用的一些试剂，并用于药物和其他高价值分子的无数合成（例如，用于电子材料和化学传感）。因此，有机硼烷、硼酸酯和硼酸衍生物在合成和药物化学中提供了一些最实用的中间体，以至于硼在有机合成中的应用已经被两次诺贝尔奖（Brown在1979年和Suzuki在2010年）所认可。尽管有这些进展，但几乎所有这些化合物都是由硼作为电子受体（亲电体）的起始材料合成的。这是硼在元素周期表中位于第13族顶部的自然结果，并且对可以制备的硼化合物的类型和种类提出了严格的限制。在这个项目中，我们将建立在我们最近的发现（自然通讯。2017，8，15022），其中硼与电负性较小的第2族元素镁键合的衍生物容易通过活化市售乙硼烷的B-B键产生。与绝大多数可用的硼试剂相反，这些化合物中的硼作为有效的电子给体（亲核试剂）反应，为合成各种新的含硼分子提供了潜力。在这个项目中，我们将应用多方面的无机/有机合成和计算方法来设计，理解和应用广泛的第2族金属（主要是镁和钙）的新型高活性硼衍生物。这些元素的吸引力突出表现在它们的毒性可以忽略不计、天然丰度高和由此产生的低成本。此外，在该项目中开发的硼亲核试剂将用于合成大量前所未有的和以前无法获得的有机和无机含硼化合物。我们的最终目标是确保这些试剂可以从商业化学品供应商处获得，并且在合成化学家的储藏室中建立以前无法获得的硼亲核试剂作为现成的试剂。

Some of the greatest benefits to human health and well-being have been provided by modern methods of chemical synthesis. Boron compounds provide some of the most widely used reagents in chemistry and are employed in myriad syntheses of pharmaceutical and other high value molecules (e.g. with uses in electronic materials and chemical sensing). Organoborane, boronate ester and boronic acid derivatives, thus, provide some of the most practically useful intermediates in synthetic and medicinal chemistry, to the extent that the application of boron in organic synthesis has been recognised by the award of two Nobel prizes (Brown in 1979 and Suzuki in 2010). Despite these advances, almost all of these compounds are synthesised from starting materials in which boron acts as an electron acceptor (electrophile). This is a natural consequence of boron's position at the top of group 13 in the periodic table and presents a severe limitation to the types and variety of boron compounds that can be made. In this project we will build on our recent discovery (Nature Commun. 2017, 8, 15022) that derivatives in which boron is bonded to a less electronegative group 2 element, magnesium, are easily generated by activation of the B-B bonds of commercially available diboranes. In contrast to the vast majority of available boron reagents, the boron in these compounds reacts as a potent electron donor (nucleophile), providing the potential to allow the synthesis of a wide variety of new boron-containing molecules. In this project, we will apply a multifaceted inorganic/organic synthetic and computational approach to devise, understand and apply a wide array of new and highly reactive boron derivatives of the group 2 metals, primarily magnesium and calcium. The attractiveness of these latter elements is underscored by their negligible toxicity, high natural abundance and resultant low cost. Furthermore, the boron nucleophiles developed in this project will be used in the synthesis of a plethora of unprecedented and previously inaccessible organic and inorganic boron-containing compounds. Our ultimate objective is to ensure that these reagents are available from commercial chemical suppliers and nothing short of establishing previously inaccessible boron nucleophiles as off-the-shelf reagents in the synthetic chemist's larder.