Silver-Catalyzed Enantioselective Sulfimidation Mediated by Hydrogen Bonding Interactions

Area of Science:

• Organic Chemistry
• Catalysis
• Asymmetric Synthesis

Background:

• Sulfimidation reactions are crucial for synthesizing sulfur-containing compounds.
• Developing enantioselective methods for sulfimidation is challenging.
• Heterocyclic lactams, such as quinolones and pyridones, are important scaffolds in medicinal chemistry.

Purpose of the Study:

• To develop a novel enantioselective sulfimidation of 3-thiosubstituted 2-quinolones and 2-pyridones.
• To investigate the key factors influencing enantioselectivity in this transformation.
• To explore the application of this method in kinetic resolution of chiral sulfoxides.

Main Methods:

• Utilized a silver-based catalyst system with a stoichiometric nitrene source (PhI=NNs).
• Employed a chiral phenanthroline ligand featuring a hydrogen bonding site.
• Analyzed reaction outcomes using enantiomeric excess (ee) measurements, ESI mass spectrometry, DFT calculations, and Hammett analysis.

Main Results:

• Achieved enantioselective sulfimidation of 3-thiosubstituted 2-quinolones and 2-pyridones.
• Synthesized 21 chiral sulfimides in high yields (44-99%) and high enantiomeric excess (70-99% ee).
• Demonstrated that enantioselectivity is governed by the binding properties of the lactams, not substituent size.

Conclusions:

• The developed silver-catalyzed system enables efficient and highly enantioselective sulfimidation.
• The reaction proceeds with high site-selectivity and can be used for kinetic resolution.
• Mechanistic studies suggest the involvement of a heteroleptic silver complex.