Oxidative Coupling of Thiols to Disulfides

Abstract

Disulfide linkages play a unique role in both biological and synthetic chemistry. As well as being vital to the structure of proteins and peptides, disulfide compounds serve as key intermediates in the synthesis of pharmacologically relevant organic molecules. The oxidative coupling of thiols is a common method for the preparation of disulfides; however it is not without challenges. Currently, many procedures face issues of over-oxidation, poor selectivity, or harsh reaction conditions. We report a mild, selective synthesis of disulfides utilizing iron-rich synthetic clay. Our clay-oxidant, Fe-Non, is cheap to produce, nontoxic, and environmentally benign. Using Fe-Non, thiols are converted cleanly to disulfides without formation of unwanted side products. Additionally, the heterogeneous clay reagent is easily recovered by a simple filtration, facilitating workup procedures. We have demonstrated the oxidative coupling of thiols at ambient temperature without additives, using Fe-Non as the oxidant.

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Oxidative Coupling of Thiols to Disulfides

Disulfide linkages play a unique role in both biological and synthetic chemistry. As well as being vital to the structure of proteins and peptides, disulfide compounds serve as key intermediates in the synthesis of pharmacologically relevant organic molecules. The oxidative coupling of thiols is a common method for the preparation of disulfides; however it is not without challenges. Currently, many procedures face issues of over-oxidation, poor selectivity, or harsh reaction conditions. We report a mild, selective synthesis of disulfides utilizing iron-rich synthetic clay. Our clay-oxidant, Fe-Non, is cheap to produce, nontoxic, and environmentally benign. Using Fe-Non, thiols are converted cleanly to disulfides without formation of unwanted side products. Additionally, the heterogeneous clay reagent is easily recovered by a simple filtration, facilitating workup procedures. We have demonstrated the oxidative coupling of thiols at ambient temperature without additives, using Fe-Non as the oxidant.