Pd‐Catalyzed Synthesis of ArSCF₃ Compounds under Mild Conditions

Abstract

Good to excellent yields of aryl trifluoromethyl sulfides, which are an important class of compounds in both the pharmaceutical and agrochemical areas, can be achieved under mild conditions by the Pd‐catalyzed reaction of aryl bromides with a trifluoromethylthiolate nucleophile (see scheme).

Cp*CoIII-catalyzed directed C–H trifluoromethylthiolation of 2-phenylpyridines and 6-arylpurines

“…Recent studies enabled a general and direct introduction of an SCF 3 group to aryl halides using trifluoromethylthiolate anion equivalents, such as AgSCF 3 , CuSCF 3 , and NR 4 SCF 3 , under transition metal-catalyzed crosscoupling conditions. [3][4][5] On the other hand, recent advances in transition metalcatalyzed directed C-H bond activation/functionalization provide an attractive strategy to site-selectively introduce various functional groups without the preparation of aryl halides or organometallic reagents. 6 In this context, several C-H trifluoromethylthiolation reactions were reported using electrophilic trifluoromethylthiolating reagents 7,8 or oxidative conditions.…”

Synthesis of 1,2-Bis(trifluoromethylthio)arenes via Aryne Intermediates

“…4 Recently, however, efficient methods utilizing milder protocols have been developed for trifluoromethylthiolation of aryl halides, boronic acids, and sp 2 C–H bonds under transition metal catalysis. 5–7 Synthesis of 1,2-bis(trifluoromethylthio)arenes has been reported in a very limited number of publications, and the reactions appear to lack generality. 8 For example, electrophilic aromatic substitution affords low yields of 1,2-bis(trifluoromethylthio)benzene.…”

Silver-Mediated Trifluoromethylation of Arenes Using TMSCF3

“…We were attracted to Ag based on the fact that it is readily available, is directly below Cu on the periodic table (suggesting the potential for similar reactivity), and has recently proven a useful promotor for other organometallic reactions. 8 There are also a number of reports describing the synthesis of AgCF 3 complexes. 9,10 However, the reactivity of these species has not been explored extensively, 9,10 thereby suggesting opportunities for new reaction discovery.…”