Novel Macrocyclisations of 2-Amino-Azines via Traceless Staudinger-SNAr-Cascade

该项目的重点是围绕药学相关的2-氨基嗪开发一种新的大环化。我们提出了一种新的试剂，将能够在温和的条件下环化2-氯-吖嗪与侧叠氮化物的发展。该试剂的模块化合成路线将提供介导有效大环化的各种膦-硫醇试剂。这种发展将有助于调查到孤立的机械步骤，特别是引发硫醇SNAr和亚氨基膦亲核芳基转移，并使用高通量实验，以优化产率和浓度。进一步的工作将集中在开发的反应的应用，以DEL和扩展的关键中间体的反应性原则，一步醇胺化。

The proposed project focuses on the development of a novel macrocyclisation centred around pharmaceutically relevant 2-amino azines. We propose the development of a novel reagent that will be able to cyclise 2-chloro-azines with pendant azides under mild conditions. A modular synthesis route for the reagent will provide access to a diverse range of phosphine-thiol reagents that mediate an efficient macrocyclisation. This development will be aided by investigations into isolated mechanistic steps, specifically the initiating thiol SNAr and the iminophosphorane nucleophilic aryl-transfer, and the use of high throughput experimentation to optimise for yield and concentration. Further work will focus on applications of the developed reaction to DELs and the extension of the reactivity principles of the key intermediate to a single step alcohol amination.