Metal-Free Direct Trifluoromethylthiolation of Aromatic Compounds Using Triptycenyl Sulfide Catalyst

Abstract

Herein we report an efficient synthetic method for the electrophilic trifluoromethylthiolation of aromatic compounds. The key is to use triptycenyl sulfide (Trip-SMe) and TfOH to enhance the electrophilicity of SCF3 fragment through the formation of sulfonium intermediates. This method enables direct installation of an SCF3 group onto unactivated aromatics at room temperature, adopting a commercially available saccharin-based reagent. Preliminary DFT calculation was carried out to investigate the substitution effect on the catalytic activity.

Recent Progress on Trifluoromethylthiolation of (Hetero)Aryl C–H Bonds with Electrophilic Trifluoromethylthiolating Reagents

“…Very recently, Miura, Nishii, and co-workers reported an efficient synthetic method for the electrophilic trifluoromethylthiolation of aromatic compounds by combined utilization of triptycenyl sulfide (Trip-SMe, 49 ) and TfOH (Scheme ). It is proposed that a more reactive species [Trip-S­(Me)­SCF 3 ] + is formed during the reaction. Moreover, charge-separated character of the species could contribute the significantly high catalytic activity.…”

Chiral Iodotriptycenes: Synthesis and Catalytic Applications

“…Very recently, triptycenyl methyl sulfide has been explored for electrophilic aromatic halogenations with N ‐halosuccinimides through the formation of sulfonium salt 1 as the active species (Figure 1a) [11] . Metal‐free trifluoromethylthiolation of aromatic compounds has also been investigated [12] . Mainly achiral triptycenes were explored in different areas of chemicals and material science, although the first synthesis of chiral triptycenes was reported in 1962 [13] .…”

“…[11] Metal-free trifluoromethylthiolation of aromatic compounds has also been investigated. [12] Mainly achiral triptycenes were explored in different areas of chemicals and material science, although the first synthesis of chiral triptycenes was reported in 1962. [13] Very recently, reviews have been published on chiral triptycenes.…”

Three-Component Friedel–Crafts Transformations: Synthesis of Alkyl and Alkenyl Trifluoromethyl Sulfides and Alkenyl Iodides

“…No reaction occurred when mesitylene and cyclohexylacetylene were mixed in HFIP without the electrophilic coupling partner (Figure a). Reaction of the aromatic substrate and (PhSO 2 ) 2 NSCF 3 without an alkyne provided modest conversion to trifluoromethylthiolated product 4 by an electrophilic aromatic substitution (Figure b). , This side reaction does not occur under the three-component conditions due to a more rapid reaction of the alkyne with the electrophilic reagent. When cyclohexylacetylene and the (PhSO 2 ) 2 NSCF 3 were reacted without an aromatic substrate, product 5 was obtained in 31% yield (Figure c).…”