posted on 2002-04-02, 00:00authored byChristian W. Tornøe, Caspar Christensen, Morten Meldal
The cycloaddition of azides to alkynes is one of the most important synthetic routes to 1H-[1,2,3]-triazoles. Here a novel regiospecific copper(I)-catalyzed 1,3-dipolar cycloaddition of terminal alkynes
to azides on solid-phase is reported. Primary, secondary, and tertiary alkyl azides, aryl azides, and
an azido sugar were used successfully in the copper(I)-catalyzed cycloaddition producing diversely
1,4-substituted [1,2,3]-triazoles in peptide backbones or side chains. The reaction conditions were
fully compatible with solid-phase peptide synthesis on polar supports. The copper(I) catalysis is
mild and efficient (>95% conversion and purity in most cases) and furthermore, the X-ray structure
of 2-azido-2-methylpropanoic acid has been solved, to yield structural information on the 1,3-dipoles
entering the reaction. Novel Fmoc-protected amino azides derived from Fmoc-amino alcohols were
prepared by the Mitsunobu reaction.