Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Nature. 2019 Oct;574(7776):86-89. doi: 10.1038/s41586-019-1589-1. Epub 2019 Oct 2.
Click chemistry is a concept in which modular synthesis is used to rapidly find new molecules with desirable properties. Copper(I)-catalysed azide-alkyne cycloaddition (CuAAC) triazole annulation and sulfur(VI) fluoride exchange (SuFEx) catalysis are widely regarded as click reactions, providing rapid access to their products in yields approaching 100% while being largely orthogonal to other reactions. However, in the case of CuAAC reactions, the availability of azide reagents is limited owing to their potential toxicity and the risk of explosion involved in their preparation. Here we report another reaction to add to the click reaction family: the formation of azides from primary amines, one of the most abundant functional groups. The reaction uses just one equivalent of a simple diazotizing species, fluorosulfuryl azide (FSON), and enables the preparation of over 1,200 azides on 96-well plates in a safe and practical manner. This reliable transformation is a powerful tool for the CuAAC triazole annulation, the most widely used click reaction at present. This method greatly expands the number of accessible azides and 1,2,3-triazoles and, given the ubiquity of the CuAAC reaction, it should find application in organic synthesis, medicinal chemistry, chemical biology and materials science.
点击化学是一种模块化合成的概念，用于快速发现具有理想性质的新分子。铜（I）催化的叠氮-炔环加成（CuAAC）三唑环化和硫（VI）氟化物交换（SuFEx）催化被广泛认为是点击反应，提供了快速获得产物的途径，产率接近 100%，同时与其他反应基本正交。然而，在 CuAAC 反应的情况下，由于叠氮试剂的潜在毒性和制备过程中的爆炸风险，其可用性受到限制。在这里，我们报告了另一种点击反应家族的反应：从伯胺形成叠氮化物，伯胺是最丰富的官能团之一。该反应仅使用一当量简单的重氮化合物氟磺酰叠氮（FSON），并且能够以安全实用的方式在 96 孔板上制备超过 1200 个叠氮化物。这种可靠的转化是 CuAAC 三唑环化的有力工具，CuAAC 三唑环化是目前最广泛使用的点击反应。该方法大大扩展了可获得的叠氮化物和 1,2,3-三唑的数量，并且鉴于 CuAAC 反应的普遍性，它应该在有机合成、药物化学、化学生物学和材料科学中得到应用。
