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

Abstract

A practical and efficient protocol toward fully substituted isothiazolones through Selectfluor-mediated intramolecular oxidative annulation of α-carbamoyl ketene dithioacetals has been developed in the presence of H 2 O and metal-free conditions. Notably, the experimental results reveal that H 2 O 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.

Transition-metal-free C–S bond cleavage and transformation of organosulfur compounds

“…Recently, the Li and Song group used Selectfluor to realize the intramolecular oxidative annulation of α-carbamoyl ketene dithioacetals 144 in the presence of H 2 O (Scheme 26c). 66 In this process, H 2 O is a crucial reagent for the preparation of multifunctionalized isothiazolones 145 . Furthermore, Selectfluor provides F + to activate the sulfur atom, generating the cyclic sulfonium salt 22E .…”