Divergent Radical and Ionic Electroreductive Regulation for Disulfuration.

Area of Science:

• Organic Chemistry
• Electrochemistry
• Medicinal Chemistry

Background:

• Disulfides are crucial in various scientific fields but challenging to synthesize due to redox sensitivity.
• Existing methods for disulfide construction often face limitations in efficiency and scope.

Purpose of the Study:

• To develop a novel electroreductive disulfuration protocol for efficient disulfide synthesis.
• To control reaction pathways (radical vs. ionic) using electrochemical potential.
• To demonstrate the protocol's utility in accessing functionalized unsymmetric disulfides.

Main Methods:

• Electrochemical reduction of a tetrasulfide precursor to generate a radical anion.
• Utilizing electrophiles with varying reduction potentials to tune reaction pathways.
• Density functional theory (DFT) calculations to elucidate reaction mechanisms.
• Gram-scaled continuous flow synthesis for scalability assessment.

Main Results:

• A novel electroreductive disulfuration protocol was established, enabling divergent synthesis of disulfides.
• Tunable radical and ionic pathways were achieved by controlling electrophile reduction potentials.
• The protocol successfully synthesized unsymmetric disulfides incorporating pharmaceutical, agrochemical, and natural product scaffolds.
• Continuous flow synthesis demonstrated robustness and scalability.
• Antibacterial activity against Staphylococcus aureus was observed, highlighting therapeutic potential.

Conclusions:

• The electroreductive disulfuration protocol provides a versatile and efficient route to diverse disulfide compounds.
• The method's ability to control reaction pathways via electrochemical switching offers significant synthetic advantages.
• The protocol's scalability and the biological activity of synthesized compounds suggest broad applicability in drug discovery and materials science.