Anionic Olefin Metathesis Catalysts Enable Modification of Unprotected Biomolecules in Water.

Stability problems have limited the uptake of cationic olefin metathesis catalysts in chemical biology. Described herein are anionic catalysts that improve water-solubility, robustness, and compatibility with biomolecules such as DNA. A sulfonate tag is installed on the cyclic (alkyl)(amino) carbene (CAAC) ligand platform, chosen for resistance to degradation by nucleophiles, base, water, and ß-elimination. Hoveyda-Grubbs catalysts bearing the sulfonated CAAC ligands deliver record productivity in metathesis of unprotected carbohydrates and nucleosides at neutral pH. Decomposed catalyst has negligible impact on metathesis selectivity, whereas N-heterocyclic carbene (NHC) catalysts degrade rapidly in water and cause extensive C=C migration.