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Updated: Jan 19, 2026

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
Published on: July 28, 2022
Relative Rates of Metal-Free Azide-Alkyne Cycloadditions: Tunability over 3 Orders of Magnitude
Patrick W Skelly1, Jirapon Sae-Jew1, Ana Paula Kitos Vasconcelos1
1Department Chemistry and Biochemistry , University of California, Santa Cruz , 1156 High Street , Santa Cruz , California 95064 , United States.
Abstract:
The thermal (3 + 2) dipolar azide-alkyne cycloaddition, proceeding without copper or strained alkynes, is an underutilized ligation with potential applications in materials, bioorganic, and synthetic chemistry. Herein, we investigate the effects of alkyne substitution on the rate of this reaction, both experimentally and computationally. Electron-withdrawing groups accelerate the reaction, providing a range of relative rates from 1.0 to 2100 between the slowest and fastest alkynes studied. Unexpectedly, aryl groups conjugated to the alkyne significantly retard the reaction rate. In contrast, a sulfonyl, ester-substituted alkyne is reactive enough that it couples with an azide at room temperature in a few hours. This reactivity scale should provide a guide to those who wish to use this ligation under mild conditions.
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