Cu(II)-Mediated C–S/N–S Bond Formation via C–H Activation: Access to Benzoisothiazolones Using Elemental Sulfur

Abstract

A copper-mediated C-S/N-S bond-forming reaction via C-H activation that uses elemental sulfur has been developed. The addition of TBAI was found to be crucial for the success of this transformation. The method is scalable, shows excellent functional group tolerance, and is compatible with heterocycle substrates, providing efficient and practical access to benzoisothiazolones. The direct diversification of the benzoisothiazolone products into a variety of sulfur-containing compounds is also demonstrated.

A Stable Anionic Dithiolene Radical

“…40 Notably, elemental sulfur has been utilized in copper-mediated C–S bond forming reactions via C–H activation. 41 While the mechanism of the transformation of 3 to 4 • remains unclear, our study reveals that this reaction requires two equivalents of elemental sulfur (Scheme 1). The corresponding 1:1 reaction only affords a mixture containing 4 • and unreacted 3 .…”

α,α-Dimethyl-2-pyridinemethanamine

“…5 It has been proposed that the gemdimethyl substitution may increase the rate of cyclization and the stability of the resulting metallacycles due to the Thorpe-Ingold effect. 5, 6 The PIP auxiliary has been widely used for the cleavage of C-H bonds and the formation of C-O, 7-9 C-C, 1b,2,10-15 C-N, 1b C-S, [16][17][18][19] and C-X 20,21 bonds. Various transition metals, such as palladium, copper, and nickel, have been used for these transformations.…”

“…Basic conditions: PIP auxiliary can be removed from benzamides by treatment with KOH and CuCl 2 in ethanol (eq 24) 16. Acidic conditions: The PIP auxiliary can also be removed under strong acidic conditions (eq 25).…”

Heterogeneously Catalyzed Direct CH Thiolation of Heteroarenes

“…[6] Pioneering work by the group of Inamoto in 2008 utilized palladium to synthesize heterocycles through homogeneous C À Ht hiolation in an intramolecular fashion. [5t] Nevertheless, ad irecting group free [8] general method for the direct CÀH functionalization of electron-rich heteroarenes,s uch as thiophene,b enzo[b]thiophene,o rb enzofuran, remains elusive. [5t] Nevertheless, ad irecting group free [8] general method for the direct CÀH functionalization of electron-rich heteroarenes,s uch as thiophene,b enzo[b]thiophene,o rb enzofuran, remains elusive.…”