Decarboxylative Triazolation Enables Direct Construction of Triazoles from Carboxylic Acids

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（Triazoles）在化学、医学与材料科学领域具有核心作用，作为一类至关重要的杂环骨架，可作为酰胺、羧酸及其他羰基基团的生物等排体替代物，同时也是点击化学（click chemistry）中应用最广泛的连接基团之一。然而，三唑类化合物的化学空间与分子多样性仍受限于合成难度较高的有机叠氮化物的可及性，该问题要求预先安装叠氮前驱体，进而限制了三唑的应用范围。本文报道了一种光催化三组分脱羧三唑化反应，该反应首次实现了羧酸与炔烃及简单叠氮试剂的单步三重催化偶联，可直接将羧酸转化为三唑。通过对脱羧三唑化反应可及化学空间的数据导向性探索，结果表明该转化策略可提升三唑类化合物结构多样性与分子复杂度的可及性。实验研究证实该合成方法具有宽泛的底物适用范围，可兼容各类羧酸、聚合物及肽类底物。当不添加炔烃时，该反应还可用于制备有机叠氮化物，从而无需预先活化步骤与专用叠氮试剂，为C-N键形成的脱羧官能团相互转化提供了一种双路径策略。