Iodine‐Catalyzed Regioselective Sulfenylation of Indoles with Sodium Sulfinates

Abstract

An iodine‐catalyzed sulfenylation of free indoles with sodium sulfinates is described. The reaction selectively afforded 3‐arylthioindoles in good to high yields in anisole under metal‐free conditions. Functional groups such as halogens were well tolerated under the optimized reaction conditions.

Direct Trifluoromethylthiolation and Perfluoroalkylthiolation of C(sp2)H Bonds with CF3SO2Na and RfSO2Na

“…During the 12 hour reaction process,f ive fluorine peaks, including those for the reagent 2b (d = À84.46 ppm), three intermediates (8 at d = À78.58 ppm, 9 at d = À62.14 ppm, and 10 at d = À45.48 ppm), and product 4a (d = À44.50 ppm) were observed (Figure 2). TheC F 3 SO 2 Na peak disappeared after 2hours.The amount of 4a increased steadily during the reaction process.T he structure of 10 was confirmed to be CF 3 SSCF 3 by its 19 FNMR data. [15b,c] To gain more information for the intermediates,weperformed four control reactions in …”

“…[5m] Development of as ystem for efficient conversion of CF 3 SO 2 Na into CF 3 SSCF 3 was the key for this project. We first examined the CF 3 SO 2 Na reaction of indole [17] in the presence of hypophosphite, [18] phosphite ester, [19] and iodotrimethylsilane [20] since they are known reducing agents for sulfonate,s ulfonate,a nd sulfoxide ( Table 1, entries 1-3). A reaction of 2equivalents of (EtO) 2 P(O)H and CF 3 SO 2 Na at 110 8 8Cw ithout using any oxidant gave the trifluoromethyl- thiolation product 4a in 32 %y ield (entry 2).…”

“…The reaction with DMSO afforded at race amount of 4a.M etal salts are able to catalyze trifluoromethylthiolation with 2b, [15] while I 2 is able to promote sulfenylation of sodium sulfinates. [19] After testing copper and silver salts,aswell as I 2 for the CF 3 SO 2 Na reactions (entries 7-13), we found that the reaction with CuCl (0.5 equiv) together with DMSO afforded ag ood amount of 4a (55 %; entry 13). Optimization of the reaction conditions (entries 10-17) revealed that using (EtO) 2 P(O)H (2.0 equiv), DMSO (3.0 equiv), and CuCl (1.0 equiv) in toluene at 110 8 8Cf or 12 hours could increase the product yield to 94 %(entry 14).…”

“…To understand the mechanism of CF 3 SO 2 Na-based direct trifluoromethylthiolation, ar eaction of indole under the optimized reaction conditions was closely monitored by 19 FNMR spectroscopy using PhCF 3 as an internal standard. During the 12 hour reaction process,f ive fluorine peaks, including those for the reagent 2b (d = À84.46 ppm), three intermediates (8 at d = À78.58 ppm, 9 at d = À62.14 ppm, and 10 at d = À45.48 ppm), and product 4a (d = À44.50 ppm) were observed (Figure 2).…”

I2-Catalyzed sulfenylation of indoles and pyrroles using triethylammonium thiolates as sulfenylating agents

“…6 Over the past years, substantial efforts have been made on developing significant and reliable methods toward 3-sulfenylindoles through C-S bond-forming reactions. A variety of sulfenylating reagents, such as sulfonium salts, 7 quinone mono-O,S-acetals, 8 sulfonyl hydrazides, 9 sulfinates, 10 disulfides, 11 sulfenyl halides, 12 N -thioimides, 13 thiols, 14 arylsulfonyl chlorides, 15 and sulfinic acids, 16 have been developed as reaction partners for coupling with indoles. However, some of those sulfenylating agents are foul-smelling and volatile, or complicated and expensive, or air- and water-sensitive.…”