To demonstrate the efficacy of the radical reactions, gramscale synthesis and isolation of the reaction products were then investigated (Fig. and Table ). Owing to the higher solubility of the radical initiator, cysteine derivatives, and unreacted maleate in aqueous solutions, the gram-scale synthesis with 0.25 M of maleic acid afforded fumaric acid in 78.1 ± 1.2% yield (1.81 ± 0.03 g) as a white solid, with a melting point of 289-293 ℃ (literature m.p.: 286-287 ℃) . By considering the ideal recovery (~90% yield) of fumaric acid from the aqueous solution, a good isolated yield was realized in the gram-scale synthesis. The conventional molecular catalyst of thiourea showed almost no reaction under identical neutral conditions (Fig. ). The combination of electron-deficient maleate and thiyl radicals will lead to an efficient release of the adduct intermediates, leading to a fast and sustained catalysis for cis-trans isomerization. As in the case of acid-catalyzed isomerization, almost no reaction (maximum 2% conversion and yield depending on the pH) was observed when starting from fumaric acid instead of maleic acid (Fig. ), which indicates that the reaction is controlled by the equilibrium of the regioisomers (thermodynamic control). When the reaction was started with angelic acid instead of maleic acid, the isomerization also proceeded, but a reversible reaction was also observed. The addition of thiyl radicals to alkenes and alkynes is well known and utilized in organic synthesis, while the corresponding isomerization reactions definitely require the subsequent elimination of thiyl units from the adduct. Some combinations of substrates with well-designed molecular catalysts having steric bulkiness can achieve the elimination reaction, leading to the catalytic cycle being closed. However, efficient catalytic isomerization requires a kinetically and thermodynamically feasible reaction pathway for the overall catalytic process to proceed with a reasonable economy. This work is, to our knowledge, the first example of efficient catalytic isomerization under mild conditions using thiols as molecular catalysts with a catalytic TON of >2,500 and TOF of 1.1 s -1 under the limiting conditions. The reactions were initiated either by thermal radical activation or photoinduced electron transfer. To unveil the enigma of the difference in reactivity, we carried out a DFT study to clarify the role of thiyl radicals.