Transition-Metal-Free Difunctionalization of Sulfur Nucleophiles

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Developing efficient synthetic routes for functionalized organic molecules is crucial in chemistry.
• Iodo-substituted sulfides are valuable intermediates for further chemical transformations.
• Existing methods often require harsh conditions or lack functional group tolerance.

Purpose of the Study:

• To develop efficient, metal-free protocols for synthesizing iodo-substituted diaryl and aryl(vinyl) sulfides.
• To explore the late-stage functionalization capabilities of these new methods.
• To establish a novel S-difunctionalization pathway for aryl(vinyl) sulfides.

Main Methods:

• Utilizing iodonium salts as electrophilic arylation and vinylation reagents.
• Employing odorless and convenient sulfur reagents under transition-metal-free conditions.
• Investigating a one-pot strategy combining diarylation and reduction.

Main Results:

• Developed efficient protocols for iodo-substituted diaryl and aryl(vinyl) sulfides.
• Demonstrated tolerance of a wide variety of functional groups in S-diarylation.
• Discovered a novel, stereoselective S-difunctionalization pathway using vinyliodonium salts.
• Achieved facile synthesis of thioanilines and a drug candidate derivative via a one-pot strategy.

Conclusions:

• The developed methods provide versatile access to iodo-substituted sulfides under mild, metal-free conditions.
• The retained iodo group enables diverse subsequent synthetic modifications.
• Mechanistic studies, including DFT calculations, support the proposed reaction pathways.