Thiyl chemistry: cysteine-catalyzed maleate isomerization via aqueous thiyl radical processes†

Abstract

Enzymatic systems efficiently catalyze the E/Z isomerization of CC double bonds by thiol-based cysteine residues, while artificial reactions utilizing thiol-based molecules have remained stoichiometric, not catalytic. Herein, we report a catalytic isomerization of maleate to fumarate under mild temperatures using molecular catalysts based on cysteine and its analogs, activated via chemical or photochemical radical processes. Kinetic analysis and density functional theory (DFT) study support an aqueous thiyl radical-catalyzed reaction. The reaction exhibits first-order dependence on the reactant concentration, zeroth-order dependence on the thiol molecule concentration, and first-order with respect to the radical initiator concentration. The catalytic turnover number of 2500 and initial catalytic turnover frequency of 1.1 s⁻¹ have been achieved on a small scale in the presence of thiyl radicals, while the gram-scale synthesis is also achieved by the aqueous thiyl catalysis. Chemical “mutational” studies reveal the importance of both the thiol unit and the intramolecular adjacent groups for efficient catalysis.