Recent Progress on Trifluoromethylthiolation of (Hetero)Aryl C–H Bonds with Electrophilic Trifluoromethylthiolating Reagents

Abstract

The incorporation of trifluoromethylthio group (−SCF 3 ) into small molecules has attracted considerable attention recently, because of its unique properties, which are beneficial for drug discovery. The preparation of trifluoromethylthiolated (hetero)arenes, a leading class of trifluoromethylthiolated compounds, is one of the hot topics in organic chemistry frontiers, and much effort have been exerted to access them. In this review, special attention is given to the preparation of (hetero)aryl C−H bonds by Friedel−Crafts-type trifluoromethylthiolation and transition-metal-catalyzed aromatic C− H bond activation/trifluoromethylthiolation with electrophilic trifluoromethylthiolating reagents.

β-Trifluorosulfinylesters: tuneable reagents for switchable trifluoromethylsulfinylation and C–H trifluoromethylthiolation

“…Replacing DMSO as a single solvent with a mixed solvent system of DMSO and CH 2 Cl 2 (1 : 1) led to a high yield of trifluoromethyl sulfide 3a, which was used directly in the next step. 16 Finally, methyl 3-((trifluoromethyl)sulfinyl)propanoate 4a was obtained in an acceptable yield via the oxidation of the corresponding sulfide in the presence of m-CPBA (for more details, see the ESI †). It is worth noting that the β-trifluorosulfinylester 4a could be simply purified by vacuum distillation, demonstrating the potential in large scale synthesis.…”

Copper‐Catalyzed Aryne Insertion into the Carbon‐Iodine Bond of Heteroaryl Iodides

“…In toluene at 90 °C, we identified L7 as the suitable ligand (entry 13), and further increasing the molar concentration of the reaction solution led to an improved yield of the desired product (entry 14). Additionally, benzene or p-xylene, with lower polarity, served as superior solvents for our reaction by ensuring the gradual and controlled formation of aryne intermediates (entries [17][18].…”

“…For instance, a C2-selective deuterated product 4 a and a novel N,P-ligand 4 b were prepared efficiently. The trifluoromethylthiolated molecule 4 c, which could be valuable for drug discovery, [18] was effortlessly generated via the direct reaction of 3 v with an air stable copper reagent. [19] Mild oxidation under acidic conditions allowed for the smooth production of pseudocyclic N-heterocycle-stabilized iodanes, [20] such as 4 d. Introduction of carboxyl (4 e), formyl [21] (4 f), vinyl (4 g), alkynyl (4 h) and heteroaryl groups (4 i, 4 j) into our products was easily achieved through cross-coupling reactions enabled by palladium catalysts.…”

Visible-light-induced dehydrogenative β-trifluoromethylthiolation of tertiary amines and direct β-trifluoromethylthiolation of enamides

“…Importantly, the visible-light-induced reaction system avoids the formation of any aromatic electrophilic substitution products. 14…”