Ene-Azide Chemistry in the Synthesis of 1,2,3-Triazoline/Triazole and Mechanistic Aspects

Abstract

Alkenes and azides have been proven to be significant synthon in organic chemistry for the preparation of diverse medicinally valued nitrogen-containing heterocycles. The ene-azide cycloaddition reaction appears as an alternative to the 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. It explores ene-azide cycloaddition reactions, detailing alkene structure/electronics effect and triazoline instability challenges. Strategies for stable triazoline/triazole synthesis using activated/strained alkenes, reaction condition impacts, and inter/intramolecular reactions are examined. Alternative triazole routes are explored. Mechanistic aspects, including triazoline transformations, are discussed with illustrative examples. Metal-catalyzed/free methods, including carbohydrate chemistry applications, are presented. The present review discloses the way for functionalization and conjugation of diverse natural products, medicinal significant scaffold, and other organic molecules, bearing olefinic functional group with required significant scaffolds. The article will be relevant to synthetic and medicinal chemist to design and develop the novel and efficient drug candidates using ene-azide chemistry.