Metal‐Free Difluoromethylthiolation, Trifluoromethylthiolation, and Perfluoroalkylthiolation with Sodium Difluoromethane‐ sulfinate, Sodium Trifluoromethanesulfinate or Sodium Perfluoro‐ alkanesulfinate

Abstract

Am ethod for direct difluoromethylthiolation of Ar À Hb onds is introduced. Thes tablea nd easy-to-handleH CF 2 SO 2 Na is reduced with (EtO) 2 P(O)H in the presence of TMSCl to generate HCF 2 S + + for the regioselective difluoromethylthiolation of aromatic compoundsi ncluding indoles, pyrroles,and activatedbenzenes. This method is also applicable for the trifluoromethylthiolationw ith CF 3 SO 2 Na and the perfluoroalkylthiolation with R f SO 2 Na of arenesa nd heteroarenes.R eaction mechanisms associated with the metal-free electrophilic fluoroalkylthiolation reactions are also discussed.

Selective Trifluoromethylthiolation and Trifluoromethylsulfinylation of Indoles with Sodium Trifluoromethanesulfinate Promoted by Phosphorus Reagents

“…On the basis of the experimental results above and previous reports, [11][12][13][14][15]22] it can be deduced that CF 3 SCl and CF 3 SOCl are formed as key intermediates in the reaction and undergo subsequent trifluoromethylthiolation and trifluoromethylsulfinylation, respectively, with 1. It can be inferred that the formation of 2a versus 3a is a competitive process.…”

“…[12] Sodium trifluoromethanesulfinate (CF 3 SO 2 Na), also known as Langlois reagent, and other sodium perfluoroalkanesulfinates are inexpensive and readily available commercial chemicals. [15] Meanwhile, Cai and co-workers reported a transition-metal-free trifluoromethylthiolation reaction of indole and its derivatives by using a CF 3 SO 2 Na/PPh 3 system and found that an additional X + source such as N-chloro-or N-bromophthalimide was essential for the reaction. [13] In 2015, Zhang et al reported a CuCl-catalyzed trifluoromethylthiolation reaction of indoles by using a CF 3 SO 2 Na/ (EtO) 2 P(O)H system.…”

“…[14] A metal-free electrophilic fluoroalkylthiolation with a similar reagent system was also achieved very recently. [15] Meanwhile, Cai and co-workers reported a transition-metal-free trifluoromethylthiolation reaction of indole and its derivatives by using a CF 3 SO 2 Na/PPh 3 system and found that an additional X + source such as N-chloro-or N-bromophthalimide was essential for the reaction. [16] Trifluoromethyl sulfides can be oxidized to give the corresponding trifluoromethyl sulfoxides.…”

POCl3‐Promoted Trifluoromethylthiolation‐Based Vicinal Bifunctionalization of Indoles with CF3SO2Na

“…of phosphorus oxychloride in N,N-dimethyl formide (DMF) at room temperature in 0.5 hour, 19 F NMR monitoring indicated that trifluoromethylsulfinylation product (3a) was obtained in 89 % yield along with trace amount of trifluoromethylthiolated compound (2a) ( Table 1, entry 1). Other solvents, such as acetonitrile, tetrahydrofuran (THF), 1,4-dioxane, toluene, dimethyl sulfoxide (DMSO) and dimethylamide (DMA), were not suitable for this reaction (entries [14][15][16][17][18][19]. Inspired by this result, we commenced searching for a suitable condition to improve the yield of bifunctionalization product (4a).…”

“…[15] As we all know, sodium trifluoromethanesulfinate (CF 3 SO 2 Na, Langlois reagent) is a cheap and easily available commercial chemical. [17] Meanwhile, Cai and co-workers also developed a direct trifluoromethylthiolation of indole derivatives with CF 3 SO 2 Na/PPh 3 system, but an additional X + source such as N-chlorophthalimide was essential for this reaction. [16] And transition-metal-free fluoroalkylthiolation reaction was achieved using a similar reagent system very recently.…”