Thiosulfate-involved Radical Sulfuration And Sulfoxidation

The organic sulfur-containing compounds almost exist in every live body. They play important roles in tranmitting life informations and expressing physiological functions. Meanwhile, they have been widely used in the areas of pharmarceuticals, materials, flavors, and dyes. Beyond the wide existence and broad application, they also possess diversified structures which caused by the multifarious valents. Sulfides and sulfoxides are two typical organic sulfur-containing compounds. However, the traditional sulfides synthesis mainly rely on the easliy-oxidized, foul, expensive thiols and thiophenols. The corresponding reactions are usually conducted under relative harsh conditions. Strong bases are always needed under non-catalytic conditions, except the ones with electron-deficient alkenes. The metalic catalytic procedures generally need high tempature and anhydrous conditions. The sulfoxides are commonly synthesized from sulfides with peroxidants or strong oxidants. It is potential dangerous and not atom-economic. The applicative importance and synthetic limitation indicate the need of greener and milder methods, which aim to realize the late-stage sulfuration and sulfoxidation in complex systems.During my doctorate studies. I focused on developing radical sulfuration and sulfoxidation with thiosulfates as sulfurating reagents and amines, amines derivatives, diphenyliodonium salts as starting materials.Part one:The radical sulfidation reactions based on amines and related derivatives.1. The sulfur atom transferred reactions involving amines. A highly efficient Cu-catalyzed dual C-S bonds formation reaction, proceeding in alcohol and water under air. is reported, in which inodorous stable Na2S2O3 is used as a sulfurating reagent. This powerful strategy provides a practical and efficient approach to construct thioethers. using readily available aromatic amines and alkyl halides as starting materials. Sensitive and synthetic useful functional groups could be tolerated. Furthermore, pharmaceuticals, glucose, an amino acid, and a chiral ligand are successfully furnished by this late-stage sulfuration strategy. The gram-scale reaction could be completed in excellent yield.2. The sulfur atom transferred reactions in aqueous conditions involving 1-aryltriazenes. We report here an efficient and mild method for constructing C-S bonds. The reactions were carried out with Na2S2O3 as a sulfurating reagent, CUSO4 as a catalyst, and water as solvent without any surfactant. The products were achieved in moderate to excellent yields at room temperature under air. Notably, this reaction is compatible with various biomolecules including amino acids, oligosaccharides, nucleosides, proteins, and cell lysates. This strategy could realize both ordinary sulfide synthesis and late-stage sulfuration of pharmaceutical in gram-scale.3. The photocatalyzed sulfuration reactions involving phenyl diazonium salts. This study presents thioether construction involving alkyl/aryl thiosulfates and diazonium salt. Electron paramagnetic resonance studies helped to demonstrate the special property of thiosulfate in this system. Transient absorption spectra, EPR experiments, and radical trapping studies helped to confirmed the electron-transfer process between [Ru(bpy)3Cl2] and 4-MeO-phenyl diazonium salt, which occurred with a rate constant of 1.69*10-9 M-1S-1. Both aryl and heteroaryl diazonium salts with various electronic properties were investigated for synthetic compatibility. Both alkyl-and aryl-substituted thiosulfates could be used as substrates. Notably, pharmaceutical derivatives afforded late-stage sulfuration smoothly under mild conditions.Part 2:Controllable photocatalyzed sulfoxidation and sulfidation from organic thiosulfate salts and diphenyliodonium salts. The sulfidation and sulfoxidation are important transformations in organic and medicinal chemistry. However, the controllable synthetic protocols for completing both processes through altering simple conditions is still a challenge. Herein, switchable sulfidation and sulfoxidation were achieved under photocatalyzed conditions by simply changing the atmosphere, which utilized the stable, non-poisonous, and odorless thiosulfate salts as sulfur sources. For the step-economical sulfoxidation, air or O2 was implied as a green oxidant. This system efficiently avoid the self-dimerization of phenyl and sulfur radical, the oxidation of phenyl radical, and the competition between oxidative and reductive quenching processes. Various sensible functional groups were tolerated in both conversions. The late stage sulfoxidation of pharmaceuticals and sugars derivatives were accomplished. Gram-scale reactions for both conversions could be succeeded.