Backstage Tour in the Development of Click Chemistry based on the Two-faced Copper

Abstract

To conjugate two azide molecules easily, I recently developed a transient protection method of cyclooctynes from cycloaddition with an azide via 1 : 1 complexation with a cationic copper(I) salt. Protection of a cyclooctyne bearing a terminal alkyne with a copper salt enabled the selective copper-catalyzed click conjugation with an azide at the terminal alkyne moiety, facilitating easy preparation of cyclooctyne derivatives.