361182-15-2

Upstream product

• 1190766-10-9 S-phenetyl 2,2,2-trifluoroethanedithioate 
• 81290-20-2 (trifluoromethyl)trimethylsilane 
• 1190766-12-1 S-phenetyl 2,2,3,3,3-pentafluoropropanedithioate 
• 66476-44-6 N-methyl-N-phenyl-S-(trifluoromethyl)thiohydroxylamine 
• 90878-19-6 phenethylmagnesium chloride 
• 103-63-9 1-phenyl-2-bromoethane 
• 622-24-2 2-phenylethyl chloride 
• 17376-04-4 2-phenethyl iodide 
• 4410-99-5 2-mercaptophenylethane 
• 2314-97-8 iodotrifluoromethane 
• 34420-17-2 (2-phenylethyl)boronic acid 
• 1584705-82-7 (((2-(2-iodophenyl)propan-2-yl)oxy)(trifluoromethyl)sulfane) 
• 1640084-14-5 (((2-phenylpropan-2-yl)oxy)(trifluoromethyl)sulfane) 
• 4455-09-8 2-phenylethyl tosylate 

Relevant academic research and scientific papers

Perfluoroalkylation of Thiosulfonates: Synthesis of Perfluoroalkyl Sulfides

A practical synthesis of perfluoroalkyl sulfides is described. The method employs stable and readily accessible thiosulfonates as new electrophiles with commercial nucleophilic perfluoroalkylating reagents. The mild reaction conditions allow access to a wide variety of both aryl- and alkyl-substituted perfluoroalkyl sulfides amenable to pharmaceutical development. Furthermore, the reaction operation is straightforward, odorless, does not produce toxic wastes, and, therefore should appeal to practitioners in industrial-scale productions.

Approach to Comparing the Functional Group Tolerance of Reactions

Herein, we describe an approach to quantifying and comparing functional group (FG) tolerance of synthetic reactions. Additive-based reaction screening is utilized as a tool for the objective comparison of reaction conditions as demonstrated in four case studies. This contributes to an understanding of factors limiting a reaction's FG tolerance and the identification of truly mild reactions.

Oxidative decarboxylative radical trifluoromethylthiolation of alkyl carboxylic acids with silver(i) trifluoromethanethiolate and selectfluor

A straightforward silver-mediated oxidative decarboxylative radical trifluoromethylthiolation reaction of aliphatic carboxylic acid is described. This reaction operates under mild conditions and allows the synthesis of various valuable alkyltrifluoromethylthioethers from abundant alkyl carboxylic acids and convenient nucleophilic AgSCF3 reagent. It provides a practical and efficient approach for the preparation of alkyltrifluoromethylthioethers.

Metal-Free Trifluoromethylthiolation of Alkyl Electrophiles via a Cascade of Thiocyanation and Nucleophilic Cyanide-CF3 Substitution

A straightforward synthesis of alkyl trifluoromethyl thioethers was developed that starts from widely available alkyl halides or mesylates and the inexpensive reagents sodium thiocyanate and trimethyl(trifluoromethyl)silane. The alkyl electrophiles are converted in situ into the corresponding thiocyanates, which react with the nucleophilic Ruppert-Prakash reagent to give the corresponding trifluoromethyl thioethers via a Langlois-type CN-CF3 substitution. This process enables the efficient introduction of the pharmaceutically meaningful trifluoromethylthio groups into functionalized molecules without the need of metal catalysts or expensive preformed trifluoromethylthiolating agents.

Structure-reactivity relationship of trifluoromethanesulfenates: Discovery of an electrophilic trifluoromethylthiolating reagent

A family of electrophilic trifluoromethanesulfenates was prepared. Structure-reactivity relationship studies showed that the substituted groups on the aryl ring of the trifluoromethylthiolating reagent did not have an obvious influence on their reactivities. A simplified electrophilic trifluoromethylthiolating reagent 1c was then identified that can react with a wide range of nucleophiles such as Grignard reagents, arylboronic acids, alkynes, indoles, β-ketoesters, oxindoles, and sodium sulfinates under mild reaction conditions. A variety of functional groups were tolerated under these conditions.

Iron-Catalyzed Decarboxylation of Trifluoroacetate and Its Application to the Synthesis of Trifluoromethyl Thioethers

Nucleophilic CF3 has been generated by decarboxylation of potassium trifluoroacetate, arguably the most easy-to-handle, inexpensive, and sustainable source of trifluoromethyl groups. Simple iron(II) chloride catalyzes the decarboxylation as well as a subsequent trifluoromethylation of organothiocyanates, resulting in a straightforward synthesis of trifluoromethyl thioethers. The KCN byproduct is absorbed by iron(II) with formation of nontoxic potassium hexacyanoferrate. An analogous trifluoromethylation of aldehydes with trifluoroacetate underlines the synthetic potential of such iron-catalyzed decarboxylative trifluoromethylations.

Difluorocarbene-Derived Trifluoromethylthiolation and [18F]Trifluoromethylthiolation of Aliphatic Electrophiles

The first trifluoromethylthiolation and [18F]trifluoromethylthiolation of alkyl electrophiles with in situ generated difluorocarbene in the presence of elemental sulfur and external (radioactive) fluoride ion is described. This transition-metal-free approach is high yielding, compatible with a variety of functional groups, and operated under mild reaction conditions. The conceptual advantage of this exogenous-fluoride-mediated transformation enables unprecedented syntheses of [18F]CF3S-labeled molecules from most commonly used [18F]fluoride ions. The rapid radiochemical reaction time (≤1 min) and high functional-group tolerance allow access to a variety of aliphatic [18F]CF3S compounds in high yields.

Copper-catalyzed synthesis of aryl and alkyl trifluoromethyl sulfides using CF3SiMe3and Na2S2O3as -SCF3source

A universal and efficient Cu(I)-catalyzed synthesis of aryl and alkyl trifluoromethyl sulfides has been developed. In this catalytic system, S-aryl or S-alkyl sulfothioate (I or II) proved to be the key intermediate. Substrates bearing groups of I, Br, Cl, OTs, and OMs on the aryl carbon and no matter electron-withdrawing and electron-donating substitutions on the aromatic ring could afford good to excellent yields.

A mild and fast photocatalytic trifluoromethylation of thiols in batch and continuous-flow

S-CF3 bonds are important structural motifs in various pharmaceutical and agrochemical compounds. However, their preparation remains a major challenge in synthetic organic chemistry. Here, we report the development of a mild and fast photocatalytic trifluoromethylation of thiols. The combination of commercially available Ru(bpy)3Cl2, visible light and inexpensive CF3I gas proved to be an efficient method for the direct trifluoromethylation of thiols. The protocol is demonstrated on a wide range of aromatic, hetero-aromatic and aliphatic substrates in both batch and continuous microflow (32 examples, 52-98% yield). Process intensification through continuous microflow application resulted in a 15-fold increase in production rate (0.25 mmol min-1) due to improved gas-liquid mass transfer, enhanced irradiation as well as convenient handling of the gaseous CF3 source. Furthermore, the efficiency of the flow process allowed to reduce the amount of CF3I (1.1 equivalent) to reach full conversion. This journal is

Efficient C(sp3alkyl)-SCF3 bond formations via copper-mediated trifluoromethylthiolation of alkyl halides

A general and convenient copper-mediated trifluoromethylthiolation of primary and secondary alkyl halides was described. Variation of the solvent, additives and time allowed optimization of the reaction. A wide range of alkyl halides were explored to give a set of alkyl trifluoromethyl thioethers in moderate to excellent yields. A variety of functional groups, including ethers, thioether, esters, nitriles, amides, and ketal groups, were well tolerated in the electrophilic partner. This journal is the Partner Organisations 2014.