Efficient preparation of unsymmetrical disulfides by nickel-catalyzed reductive coupling strategy

The preparation of disulfides mainly relies on oxidative couplings of two sulfur-containing compounds, a strategy which has side reactions and other shortcomings. In this work, the authors present a reductive nickel-catalyzed cross-electrophile coupling of unactivated alkyl bromides with symmetrical tetrasulfides to form unsymmetrical disulfides, proceeding via trisulfide intermediates. Disulfides are widely found in natural products and find a wide range of applications in life sciences, materials chemistry and other fields. The preparation of disulfides mainly rely on oxidative couplings of two sulfur containing compounds. This strategy has many side reactions and other shortcomings. Herein, we describe the reductive nickel-catalyzed cross-electrophile coupling of unactivated alkyl bromides with symmetrical alkyl- and aryltetrasulfides to form alkyl-alkyl and aryl-alkyl unsymmetrical disulfides. This approach for disulfide synthesis is practical, relies on easily available, unfunctionalized substrates, and is scalable. We investigated the mechanism of this transformation and found that the tetrasulfide compound does not selectively break the central S-S bond, but regio-selectively generates trisulfide intermediates.

Automated summary

In this work, the authors present a new method for the synthesis of disulfides through a reductive nickel-catalyzed cross-electrophile coupling of unactivated alkyl bromides with symmetrical tetrasulfides, forming unsymmetrical disulfide intermediates. This approach offers practicality and scalability for disulfide synthesis.