Direct Access to SCF₃-Substituted 2H-Thiopyrans Via a [4 + 2] Annulation with 1,3-Dienes, AgSCF₃, and KI

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Trifluoromethylthio (CF3S) groups are important functional groups in medicinal chemistry and materials science.
• Developing efficient methods for introducing CF3S groups is crucial for synthetic chemists.

Purpose of the Study:

• To establish a novel [4 + 2] annulation reaction for synthesizing CF3S-substituted 2H-thiopyrans.
• To explore the scope and efficiency of this new synthetic methodology.

Main Methods:

• A [4 + 2] annulation reaction involving 1,3-dienes, silver trifluoromethanethiolate (AgSCF3), and potassium iodide (KI).
• In situ generation of the key intermediate bis(trifluoromethylthio)methanedithione ((CF3S)2C=S) from AgSCF3 and KI under mild conditions.

Main Results:

• Successfully synthesized a variety of CF3S-substituted 2H-thiopyrans.
• Achieved high chemo- and regioselectivities in the annulation reaction.
• Demonstrated the reaction's advantages: readily available starting materials, broad substrate scope, operational simplicity, and high atom economy.

Conclusions:

• The developed [4 + 2] annulation provides an effective route to CF3S-substituted 2H-thiopyrans.
• This method offers a practical and atom-economical approach for incorporating the CF3S moiety into organic molecules.