A Chemoselective and Copper-Catalyzed Azide–Alkyne Cycloaddition (CuAAC)/Ring-Cleavage/Cyclization Reaction Sequence Leading to Pyrimidin-4-imines
Abstract
The privileged pyrimidin-4-imine scaffold is of interest in both chemical and pharmacological research. Herein, we detail the development of a chemoselective, copper-catalyzed azide-alkyne cycloaddition (CuAAC)/ring-cleavage/cyclization strategy for the synthesis of various pyrimidin-4-imine derivatives. At higher temperatures (80 °C), the copper(I)-catalyzed, three-component reaction of ynones, sulfonyl azides, and amidines selectively affords a cycloaddition/fragmentation product. In contrast, at room temperature (rt, ca. 25 °C), in water-miscible solvents, and in a remarkably chemoselective process, the formation of pyrimidin-4-imines is now favored.
Fields of Study & Subjects
Click Chemistry and Applications
Catalytic Alkyne Reactions
Multicomponent Synthesis of Heterocycles
Publication details
- Journal / source
- The Journal of Organic Chemistry
- Volume
- 91
- Issue
- 4
- Pages
- 1869–1874
- Publication date
- 15 January 2026
- Language
- EN