Metal-free reductive desulfurization of C-sp³-substituted thiols using phosphite catalysis

Area of Science:

• Organic Chemistry
• Synthetic Methodology
• Radical Chemistry

Background:

• Phosphorus(III) compounds like phosphines and phosphites are vital for non-metal desulfurization due to the strong phosphorus-sulfur bond.
• Existing desulfurization methods typically require stoichiometric or excess amounts of phosphorus(III) reagents, limiting their efficiency and atom economy.
• A catalytic approach for phosphine/phosphite-mediated desulfurization has remained an elusive goal in synthetic chemistry for decades.

Purpose of the Study:

• To develop a novel desulfurization methodology that operates catalytically with phosphites.
• To integrate thermal radical processes for efficient thiol desulfurization and phosphorus(V) sulfide reduction.
• To establish a practical and versatile method for the synthesis of organic sulfur compounds.

Main Methods:

• A combined thermal radical process involving catalytic trimethyl phosphite and azo-bis(cyclohexyl)nitrile.
• Utilized tris(trimethylsilyl)silane as both a stoichiometric reductant and a sulfur atom scavenger.
• Applied the method to the desulfurization of both activated and unactivated alkyl thiols.

Main Results:

• Successfully achieved catalytic desulfurization of alkyl thiols using catalytic trimethyl phosphite.
• Demonstrated the reduction of phosphorus(V) sulfide to phosphorus(III) via a silyl radical intermediate.
• Obtained good to excellent yields of desulfurized products, with tolerance for common organic functional groups.

Conclusions:

• This study reports the first catalytic phosphine/phosphite-mediated desulfurization process.
• The developed method merges two thermal radical processes, offering an efficient synthetic route.
• The catalytic approach represents a significant advancement in desulfurization methodologies, enhancing sustainability in organic synthesis.