Direct Trifluoromethylthiolation of Unactivated C(sp³)H Using Silver(I) Trifluoromethanethiolate and Potassium Persulfate

Abstract

A practical and efficient method for the direct trifluoromethylthiolation of unactivated C(sp(3) )H bonds by AgSCF3 /K2 S2 O8 under mild conditions is described. The reaction has a good functional-group tolerance and good selectivity. Initial mechanistic investigations indicate that the reaction may involve a radical process in which K2 S2 O8 plays key roles in both the activation of the C(sp(3) )H bond and the oxidation of AgSCF3 .

C–H Xanthylation: A Synthetic Platform for Alkane Functionalization

“…23 Recent reports of aliphatic C–H trifluoromethylthiolation using AgSCF 3 and persulfate oxidants have emerged, but are generally selective for tertiary C–H bonds and often require excess substrate to obtain synthetically useful yields. 24 We have developed simple conditions to introduce the trifluoromethylthiol group from alkyl xanthates using an easily accessible reagent developed by Shen, as shown in the preparation of 32 . 25 This provides a general approach to formal aliphatic C–H trifluoromethylthiolation using substrate as limiting reagent, appropriate for late-stage functionalizations of complex substrates.…”

Silver-Mediated Direct sp3 C–H Bond Functionalization

“…It is important to note that more complex natural products were successfully applied in this trifluoromethylthiolation, exhibiting the potential of this method in medicinal chemistry. Almost at the same time, Chen and coworkers also reported the similar direct trifluoromethylthiolation of sp 3 C-H bonds by AgSCF 3 /K 2 S 2 O 8 [46]. They also used AgSCF 3 as trifluoromethylthiolation reagent, but K 2 S 2 O 8 as the oxidant.…”

“…Very recently, both Tang and Chen groups have reported direct sp 3 C-H trifluoromethylthiolation using silver (І) trifluoromethanethiolate and persulfate [45,46]. These developed methods were applied for the late-stage trifluoromethylthiolation of pharmaceutical and agrochemical compounds.…”

Visible‐Light‐Promoted Trifluoromethylthiolation of Styrenes by Dual Photoredox/Halide Catalysis

“…One contributing factor to this discrepancy is the relative lack of reliable methods to access the SCF 3 radical. The most common approach, which has been recently employed in many impressive transformations, involves the in situ oxidation of the nucleophilic trifluoromethylthiolating reagent AgSCF 3 ,,. However, this method requires super‐stoichiometric amounts of a strong oxidant.…”