Selectfluor-Promoted Intramolecular N-S Bond Formation of α-Carbamoyl Ketene Dithioacetals in the Presence of Water: Synthesis of Multifunctionalized Isothiazolones

A practical and efficient protocol toward fully substituted isothiazolones through Selectfluor-mediated intra-molecular oxidative annulation of alpha-carbamoyl ketene dithioacetals has been developed in the presence of H2O and metal-free conditions. Notably, the experimental results reveal that H2O was crucial to the formation of new N-S bonds and the elimination of alkyl group from the sulfur atom. This protocol provides readily prepared substrates and possesses good functional group tolerance, mild reaction conditions, and operational simplicity, which provides potential access to applications in the pharmaceutical chemistry.

Automated summary

A new synthetic method was developed for the synthesis of fully substituted isothiazolones using water-mediated reaction conditions, which showed good functional group tolerance, mild reaction conditions, and operational simplicity, providing a potential pathway for applications in pharmaceutical chemistry.