Copper-catalyzed intramolecular N-S bond formation by oxidative dehydrogenative cyclization

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Intramolecular cyclization reactions are crucial for constructing heterocyclic compounds.
• The formation of nitrogen-sulfur (N-S) bonds is a key step in synthesizing various biologically active molecules.
• Developing efficient and scalable synthetic methodologies for complex heterocycles remains an active area of research.

Purpose of the Study:

• To develop a novel copper-catalyzed protocol for the synthesis of benzo[d]isothiazol-3(2H)-ones and N-acyl-benzothiazetidines.
• To investigate the formation of a new nitrogen-sulfur (N-S) bond through intramolecular dehydrogenative cyclization.
• To demonstrate the utility of this method for synthesizing drug intermediates.

Main Methods:

• Copper-catalyzed intramolecular dehydrogenative cyclization reaction.
• Utilizing N-H and S-H coupling for new N-S bond formation.
• Gram-scale synthesis and functional group tolerance studies.

Main Results:

• Successful synthesis of benzo[d]isothiazol-3(2H)-ones and N-acyl-benzothiazetidines.
• Efficient formation of the nitrogen-sulfur (N-S) bond via N-H/S-H coupling.
• Demonstrated high functional group tolerance and scalability (gram scale).
• Facilitated double cyclization for drug intermediate synthesis.

Conclusions:

• A novel and efficient copper-catalyzed method for synthesizing valuable N-S containing heterocycles has been established.
• The developed protocol offers high functional group tolerance and scalability, making it suitable for practical applications.
• This methodology provides a new route for the synthesis of important drug intermediates.