Dang Hang T, Nguyen Viet D, Haug Graham C, Arman Hadi D, Larionov Oleg V
Department of Chemistry, The University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249, United States.
JACS Au. 2023 Feb 16;3(3):813-822. doi: 10.1021/jacsau.2c00606. eCollection 2023 Mar 27.
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.
三唑在化学、医学和材料科学中发挥着重要作用，是极为重要的杂环基序，也是酰胺、羧酸和其他羰基的生物电子等排体替代物，同时还是点击化学中一些使用最广泛的连接基。然而，三唑的化学空间和分子多样性仍然受到合成难度较大的有机叠氮化物可及性的限制，因此需要预先安装叠氮化物前体并限制了三唑的应用。我们在此报告了一种光催化的三组分脱羧三唑化反应，该反应首次实现了羧酸在与炔烃和一种简单叠氮化物试剂的一步三催化偶联中直接转化为三唑。对脱羧三唑化可及化学空间的数据导向探究表明，这种转化可以改善对三唑结构多样性和分子复杂性的获取。实验研究证明了该合成方法具有广泛的适用范围，适用于多种羧酸、聚合物和肽底物。当在没有炔烃的情况下进行时，该反应还可用于制备有机叠氮化物，从而避免了预活化和特殊的叠氮化物试剂，并提供了一种双管齐下的方法来进行形成C-N键的脱羧官能团相互转化。
