C-S cross-coupling for the synthesis and modification of sulfoximines

亚砜亚胺是一种四面体硫（IV）官能团，其在构型和组成上都是稳定的。它具有一系列重要的药代动力学特性;例如增加水溶性和代谢稳定性。该官能团还具有手性，并将另一个立构中心引入目标化合物中。这导致磺酰亚胺最近被修饰到一系列先导化合物上，但是对于其独特官能团的后期引入存在合成限制，并且目前还没有通过形成C-S键来后期添加官能团的方法。开发温和的绿色一步反应来引入亚砜亚胺官能团将是迈向更可持续的合成的一步。这种性质的反应将减少目前掺入亚砜亚胺所需的溶剂和试剂的浪费使用。提出的解决方案是金属催化的交叉偶联反应，包括芳基硼酸或酯与用离去基团修饰的亚砜亚胺的偶联。本发明的目的是在室温下在绿色溶剂中使用丰富且廉价的金属催化剂如铜或铁进行反应。

A sulfoximine is a tetrahedral sulfur(IV) functional group that is both configurationally and constitutionally stable. It has a range of important pharmacokinetic properties; such as increasing aqueous solubility and metabolic stability. The functional group also has chirality and introduces another stereocentre into a target compound. This has led to sulfoximines recently being modified onto a range of lead compounds, but there are synthetic limitations for the late-stage introduction of their unique functionality and currently there is not a method for the late-stage addition of the functional group through the formation of a C-S bond. The development of a mild green one-step reaction to introduce the sulfoximine functionality will be a step towards more sustainable syntheses. A reaction of this nature would reduce the wasteful use of solvents and reagents currently required to incorporate a sulfoximine. As well as making the quick synthesis of a library of sulfoximine modified lead compounds viable.The proposed solution is a metal catalysed cross-coupling reaction, involving the coupling of an aryl boronic acid or ester with a sulfoximine modified with a leaving group. The intention is to perform the reaction at room temperature in a green solvent using an abundant and cheap metal catalyst such as copper or iron.