Synthesis of Benzo-Fused Sulfonimidate Heterocycles

Area of Science:

• Organic Chemistry
• Heterocyclic Chemistry

Background:

• Sulfonimidate heterocycles are valuable scaffolds in medicinal chemistry.
• Efficient synthetic routes to novel heterocyclic systems are in high demand.

Purpose of the Study:

• To develop a novel, efficient two-step synthesis for benzo-fused sulfonimidate heterocycles, specifically Benzo[e][1,2,3]oxathiazin-4-one-2-oxides.
• To demonstrate the synthesis of both enantiomers of these heterocycles and confirm the stereochemical outcome.
• To explore the synthetic utility and practicality of the developed method.

Main Methods:

• Two-step synthesis involving sulfonimidate ester formation from tert-butyl N-sulfinyl carbamate and methyl salicylate.
• Acid-catalyzed cyclization of sulfonimidate esters to form the benzo-fused heterocycles.
• Synthesis of enantiomerically pure compounds using enantiomerically pure sulfinyl carbamates, confirmed by X-ray crystallography.

Main Results:

• Efficient synthesis of novel Benzo[e][1,2,3]oxathiazin-4-one-2-oxides reported.
• Successful synthesis of both enantiomers with inversion of configuration at the sulfur center.
• Gram-scale synthesis and mechanochemical methods confirmed practicality; late-stage functionalization demonstrated.

Conclusions:

• A robust and efficient synthetic strategy for Benzo[e][1,2,3]oxathiazin-4-one-2-oxides has been established.
• The method allows for stereoselective synthesis of chiral sulfonimidate heterocycles.
• The developed protocol offers broad synthetic utility and potential for further derivatization.