Triazines: Syntheses and Inverse Electron-demand Diels-Alder Reactions

Triazines are an important class of six-membered aromatic heterocycles possessing three nitrogen atoms, resulting in three types of regio-isomers: 1,2,4-triazines (alpha-triazines), 1,2,3-triazines (v-triazines), and 1,3,5-triazines (s-triazines). Notably, the application of triazines as cyclic aza-dienes in inverse electron-demand Diels-Alder (IEDDA) cycloaddition reactions has been established as a unique and powerful method in N heterocycle synthesis, natural product preparation, and bioorthogonal chemistry. In this review, we comprehensively summarize the advances in the construction of these triazines via annulation and ring-expansion reactions, especially emphasizing recent developments and challenges. The synthetic transformations of triazines are focused on IEDDA cycloaddition reactions, which have allowed access to a wide scope of heterocycles, including pyridines, carbolines, azepines, pyridazines, pyrazines, and pyrimidines. The utilization of triazine IEDDA reactions as key steps in natural product synthesis is also discussed. More importantly, a particular attention is paid on the bioorthogonal application of triazines in fast click ligation with various strained alkenes and alkynes, which opens a new opportunity for studying biomolecules in chemical biology.

Automated summary

This review highlights the importance and applications of triazines, a class of six-membered aromatic heterocycles, in the synthesis of N heterocycles, natural product preparation, and bioorthogonal chemistry. It discusses the construction of triazines through annulation and ring-expansion reactions, emphasizing their role in IEDDA cycloaddition reactions for accessing a wide scope of heterocycles. Furthermore, it explores the bioorthogonal application of triazines in fast click ligation with strained alkenes and alkynes, providing a new opportunity for studying biomolecules in chemical biology.