Decarboxylative Triazolation Enables Direct Construction of Triazoles from Carboxylic Acids.
Decarboxylative Triazolation Enables Direct Construction of Triazoles from Carboxylic Acids.
复制标题
DOI：
10.1021/jacsau.2c00606
复制
发表时间：
2023-03-27
期刊：
影响因子：
8
通讯作者：
Larionov, Oleg V
中科院分区：
文献类型：
--
作者：
Dang, Hang T;Nguyen, Viet D;Haug, Graham C;Arman, Hadi D;Larionov, Oleg V
三唑在化学、医学和材料科学中具有重要作用，作为重要的杂环基序和酰胺、羧酸和其他羰基的生物电子等排替代物，以及点击化学中最广泛使用的一些连接体。然而，三唑的化学空间和分子多样性仍然受到合成上具有挑战性的有机叠氮化物的可及性的限制，从而需要预先安装叠氮化物前体并限制三唑的应用。我们在此报告的光催化，三组分脱羧三唑化反应，第一次能够直接转换的羧酸三唑在一个单一的步骤，三重催化耦合与炔和一个简单的叠氮试剂。对脱羧三唑化反应的可及化学空间的数据引导查询表明，该转化可以改善三唑的结构多样性和分子复杂性。实验研究证明了广泛的合成方法，包括各种羧酸，聚合物和肽底物。当在不存在炔的情况下进行时，该反应也可以用于获得有机叠氮化物，从而避免预活化和专门的叠氮化物试剂，并为C-N键形成脱羧官能团相互转化提供了一种双管齐下的方法。
Triazoles have major roles in chemistry, medicine, and materials science, as centrally important heterocyclic motifs and bioisosteric replacements for amides, carboxylic acids, and other carbonyl groups, as well as some of the most widely used linkers in click chemistry. Yet, the chemical space and molecular diversity of triazoles remains limited by the accessibility of synthetically challenging organoazides, thereby requiring preinstallation of the azide precursors and restricting triazole applications. We report herein a photocatalytic, tricomponent decarboxylative triazolation reaction that for the first time enables direct conversion of carboxylic acids to triazoles in a single-step, triple catalytic coupling with alkynes and a simple azide reagent. Data-guided inquiry of the accessible chemical space of decarboxylative triazolation indicates that the transformation can improve access to the structural diversity and molecular complexity of triazoles. Experimental studies demonstrate a broad scope of the synthetic method that includes a variety of carboxylic acid, polymer, and peptide substrates. When performed in the absence of alkynes, the reaction can also be used to access organoazides, thereby obviating preactivation and specialized azide reagents and providing a two-pronged approach to C–N bond-forming decarboxylative functional group interconversions.