The trifluoromethylthio group(-SCF3) has attracted escalating interest as a potentially-significant functional group from both academia and pharmaceutical and argochemical industries, due to its high lipophilicity and strong electron-withdrawing effect. Incorporation of the trifluoromethylthio group into leading drug candidates, e.g. replacement of popular CF3 moiety, has become an indispensible strategy for drug design to control bioavailability and cell-membrane permeability of original compounds. There are four representative examples of trifluoromethylthiolated compounds,such asthe coccidiostatic Toltrazuril, the parenteral cephalosporin Cefazaflur, the Dopamine antagonists, and the inhibitor of ubiquitin-activating enzyme for the treatment of cell proliferation disorders TAK-243.
Many methods to obtain SCF3-substituted compounds have been developped and reported in the past decades. Their strategies can be basically divided into the following three approches:
1.Indirect Trifluoromethylthiolation. A number of synthetic methods exist to accomplish this transformation, e.g. the nucleophilic, electrophilic and radical trifluoromethylation of disulfides,thipocyanates,thiols and thiolates with a trifluoromethylating reagents. However, these synthetic tools to access this moiety are fairly limtied by their need for the preparation of sulfur precursors, a narrow substrate scope and often a requirement of hgih temperature.
2. Direct Nucleophilic Trifluoromethylthiolation. Some methods for direct formation of SCF3 group have been developed, such as copper(I) trifluoromethanethiolate (CuSCF3,kumi3F20) , a good nucleophilic trifluoromethylthiolating reagents in earier times and (bpy)CuSCF3(kumi3F21) developed more recently, an air-stable copper reagent with high efficience in this direct transformation for various aryl halides into the corresponding trifluoromethylthiolated compound in modest to good yields. To be noted, the direct nucleophilic methods with CF3S- anion often require the use of stoichiometric amount of metals to stabilize this quite unstable anion.
3. Direct Electrophilic Trifluoromethylthiolation. The first and simplest electronic trifluoromethylthiolating reagent was trifluoromethylsulfenyl chloride(CF3SCl). Although it can react with a varity of nucleophiles, the gaseous and toxic nature of this reagent restricts its further untilzation. Afterwards, Some electrophilic trifluoromethylthilating reagents, safer to use and easier to handle, have been developped as a potentially valuable replacement to CF3Cl. One representative example is N-trifluoromethylthiosaccharin reagent (kumi3F03) developed by Shen and his group recently. This new reagent has been proved to be a versatile electrophilic trifluoromethylthiolation toolbox by converting a broad range of substrates,e.g. alcohols,aldehydes, ketones,eletron-rich arenes and alkynes into the target trifluromethylthiolated products in good yields under mild conditions.
Kumidas preferably provide you with these shelf-stable,versatile,readliy available and easy-to-handle reagents for the purpose of straightforward trifluoromethylthiolation.
Trifluoromethylthiolating Reagents Overview
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You can either buy our trifluoromethylthiolating reagents and then introduce trifluoromethylthio group into your own desired compounds, or you can simply order the building blocks pre-loaded with the -SCF3 subsitituent.
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