N-Sulfenylation of β-Lactams: Radical Reaction of N -Bromo-azetidinones by TEMPO Catalysis.

Azetidinones with a sulfenyl group on the β-lactam nitrogen atom show interesting biological activities as antimicrobial agents and enzyme inhibitors. We report in the present study a versatile synthesis of N -sulfenylated azetidinones starting from the corresponding N -bromo derivatives by means of the (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) radical as the catalyst and disulfides. Preparation of N -halo-azetidinones was studied and optimized. The reactivity of N -bromo-azetidinone 2a as a model compound in the presence of TEMPO radical was investigated by NMR and electron paramagnetic resonance (EPR) spectroscopy studies. Optimization of the reaction conditions allowed the access of N -alkylthio- or N -arylthio-azetidinones from 55 to 92% yields, and the method exhibited a good substrate scope.