Selectfluor-Mediated C(sp³)-H Phenoxylation/Cyclization toward Seven-Membered S,O-Heterocycles

Area of Science:

• Organic Chemistry
• Heterocyclic Chemistry
• Synthetic Methodology Development

Background:

• Thioethers are versatile building blocks in organic synthesis.
• Developing efficient methods for constructing S,O-heterocycles is crucial for medicinal chemistry and materials science.
• Existing methods for α-C(sp3)-H functionalization of thioethers often require harsh conditions or lack functional group tolerance.

Purpose of the Study:

• To develop a novel intramolecular α-C(sp3)-H phenoxylative cyclization of thioethers.
• To establish a mild and efficient method for constructing seven-membered S,O-heterocyclic scaffolds.
• To expand the synthetic toolbox for functionalizing thioethers with oxidation-sensitive nucleophiles.

Main Methods:

• Intramolecular cyclization of thioethers using phenols as nucleophiles.
• Employing Selectfluor as a mild oxidant for the phenoxy-Pummerer transformation.
• Optimization of reaction conditions to achieve high efficiency and functional group tolerance.

Main Results:

• Successfully synthesized seven-membered S,O-heterocyclic scaffolds with high yields.
• Demonstrated excellent functional group tolerance under the developed reaction conditions.
• Established a new phenoxy-Pummerer transformation for α-C(sp3)-H functionalization of thioethers.

Conclusions:

• The developed method provides an efficient and mild route to valuable S,O-heterocyclic compounds.
• This work expands the scope of α-C(sp3)-H functionalization of thioethers.
• The new synthetic paradigm enables the incorporation of oxidation-sensitive nucleophiles under mild conditions.