Origins of halogen effects in bioorthogonal sydnone cycloadditions

Chem Commun (Camb). 2018 May 15;54(40):5082-5085. doi: 10.1039/c8cc02128g.

Abstract

Halogen substituents increase sydnone cycloaddition reactivities substantially. Fluoro-sydnones are superior to bromo- and chloro-sydnones, and can achieve extremely high second-order rate constants with strained alkynes. Computational studies have revealed the fluorine substituent increases the reactivity of sydnone mainly by lowering its distortion energy.