PPh₃-Promoted Sulfa-Michael Addition-Driven Cyclization: A Divergent Route to Access Spirothiochromanone Derivatives

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Spirocyclic compounds are important scaffolds in medicinal chemistry.
• Efficient synthesis of sulfur-containing heterocycles remains a challenge.

Purpose of the Study:

• To develop a novel, efficient synthetic route for spirothiochromanone derivatives.
• To utilize a new sulfur surrogate for cascade reactions.

Main Methods:

• Triphenylphosphine-mediated sulfa-Michael addition-triggered cascade reaction.
• Utilized 3H-benzo[c][1,2]dithiol-3-one as a sulfur surrogate.
• Reductive S-S bond cleavage initiated the reaction.

Main Results:

• Successfully synthesized diverse spiro-1,3-dimethylbarbiturate-thiochromanones and spiro-1,3-indanedione-thiochromanones.
• Achieved good to excellent conversions under mild conditions.
• Demonstrated operational simplicity, scalability, and functional group compatibility.

Conclusions:

• Developed a valuable strategy for constructing complex sulfur-containing spirocyclic scaffolds.
• The protocol obviates the need for column chromatography, simplifying purification.
• Highlights the utility of the novel cascade reaction for synthesizing spirothiochromanones.