Diversification of Trifluoromethylthiolation of Aromatic Molecules with Derivatives of Trifluoromethanesulfenamide

Abstract

Trifluoromethylthiolation of aromatic compounds with different electrophilic reagents of the type ArNHSCF3 was studied in the presence of triflic acid as an activator. The effect of the reagent structure on the reactivity was studied with three different reagents: PhNHSCF3 (H/SCF3, 1a), 4‐ClC6H4NHSCF3 (Cl/SCF3, 1b) and C6F5NHSCF3 (F5/SCF3, 1c). p‐Chloro substituted reagent 1b was more stable than the unsubstituted 1a and was the most effective because it could not react by trifluoromethylthiolation of itself. This reaction was the most important side reaction of 1a. The pentafluoro derivative 1c was less reactive. Solvent played an important role in the transformation and, depending on the substrate, dichloromethane, hexane or trifluoroacetic acid gave the best yield of various trifluoromethylthiolated aromatic molecules (63–98 %).

One pot synthesis of trifluoromethyl aryl sulfoxides by trifluoromethylthiolation of arenes and subsequent oxidation with hydrogen peroxide

“…Due to limited commercial availability, a library of triuoromethyl suldes 1 was prepared from various activated and deactivated aromatic substrates using our method with p-ClPhNHSCF 3 . 35 The best conditions for the preparation of 2a (1.2 equiv. of 30% H 2 O 2 , 0 C, TFA) were applied.…”

“…Indole and benzothiophene were selectively transformed to the corresponding triuoromethylthiolated derivatives 1n and 1o, respectively. 35 Indole was selectively and quantitatively triuoromethylthiolated to give 3-((tri-uoromethyl)thio)-1H-indole 1n, which was oxidized under the standard reaction conditions to the desired triuoromethyl sulfoxide 2n and isolated in 33% yield (Scheme 3). A lower yield is attributed to the formation of a complex mixture of products.…”

“…The reaction conditions for the preparation of triuoromethyl suldes 1 were taken from the reported reaction conditions. 35 A solution of substrate 1 0 , reagent p-ClPhNHSCF 3 , activator TfOH and solvent was stirred for 20 h at room temperature. The choice of the solvent depended on the reactivity of the arene (DCM, hexane or TFA).…”

“…6,31,32 One of the most commonly and widely used reagent is the Billard reagent PhNHSCF 3 , 33,34 while reagent p-ClPhNHSCF 3 is suited for the use on wider range of arenes. 35 We present in this report effective, simple and highly selective method for the one-pot synthesis of various aryl triuoromethyl sulfoxides from different activated and deactivated aromatic molecules by triuoromethylthiolation with the stable and easy to use reagent p-ClPhNHSCF 3 , 35 followed by oxidation with H 2 O 2 in TFA (Scheme 2).…”

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

“…A similar trend was observed in our previous study on sulfonium intermediates. 17 Notably, in case the reagent VI is used instead of VII, such a spectral change was not observed upon treatment with TfOH. This is consistent with the result in Table 1 (entry 2 vs 5).…”