Alkenes and azides have been proven to be significant synthons in organic chemistry for the preparation of diverse medicinally valued nitrogen-containing heterocycles. The ene-azide cycloaddition reaction appears as an alternative to azide-alkyne cycloaddition for the synthesis of 1,2,3-triazole building blocks. This review surveys 1,2,3-triazole/triazoline synthesis, focusing on non-click techniques, and explores ene-azide cycloaddition reactions, detailing alkene structure/electronic effects and challenges associated with triazoline instability. Strategies for stable triazoline/triazole synthesis using activated/strained alkenes, effects of reaction conditions, and inter/intramolecular reactions are examined. Alternative triazole routes are also explored. Mechanistic aspects including triazoline transformations are discussed with illustrative examples. Metal-catalyzed/free methods including applications of carbohydrate chemistry are presented. This review discloses various approaches for the functionalization and conjugation of diverse natural products, medicinally significant scaffolds, and other organic molecules, bearing olefinic functional groups with the required scaffolds. This review could guide synthetic and medicinal chemists to design and develop novel and efficient drug candidates using ene-azide chemistry.

烯烃和叠氮化物已被证明是有机化学中制备具有药物价值的含氮杂环的重要合成子。烯-叠氮加成反应作为一种替代方法，用于通过合成1,2,3-三唑构建块来代替叠氮-炔烃环加成反应。本文综述了1,2,3-三唑/三唑啉的合成，并重点介绍了非点击技术以及烯-叠氮加成反应，详细讨论了烯烃结构/电子效应和与三唑啉不稳定相关的挑战。文中还探讨了使用活化/应变烯烃进行稳定三唑啉/三唑合成的策略、反应条件的影响以及间/内分子反应。此外，本文还探索了一些替代的三唑合成途径，并通过具体示例讨论了包括三唑啉转化在内的机理方面。文中介绍了金属催化/自由方法的应用，其中包括糖化学的应用。这篇综述披露了各种用于功能化和连接具有所需骨架的不同天然产物、药物重要支架和其他有机分子的方法，这些方法基于带有烯烃官能团的底物。本文可以指导合成化学家和药学化学家利用烯-叠氮化学设计和发展新的高效候选药物。