Difluoromethyl Thioethers Research Articles

Synthesis of (benzenesulfonyl)difluoromethyl thioethers from ((difluoromethyl)sulfonyl)benzene and organothiocyanates generated in situ

Easily available aryl and alkyl thiocyanates were converted into the corresponding (benzenesulfonyl)difluoromethyl thioethers via the direct nucleophilic substitution of ((difluoromethyl)-sulfonyl)benzene under transition metal free conditions. Combined with various thiocyanation methods, this reaction can allow late-stage (benzenesulfonyl)difluoromethylthiolation of alkyl halides and aryl diazonium salts.

Metal-free, oxidative decarboxylation of aryldifluoroacetic acid with the formation of the ArS-CF2 bond.

A metal-free, oxidative decarboxylative reaction of aryldifluoroacetic acids with diaryl disulfides or thiols under mild reaction conditions has been developed. This is an efficient and straightforward radical cross-coupling method for the synthesis of diverse aryldifluoromethylthio ethers in moderate to excellent yields.

Synthesis of difluoromethyl and deuterium-labeled difluoromethyl thioethers from aliphatic electrophiles.

A one-pot difluoromethylthiolation of alkyl electrophiles with thiourea and diethyl bromodifluoromethylphosphonate is described. The transition-metal-free approach, readily available reagents, and mild conditions provide a practical way for the synthesis of difluoromethyl thioethers. By changing the "H" source to the most commonly used "D" sources CD3OD and D2O, this strategy enables efficient synthesis of SCF2D-substituted molecules in good yields with high levels of D incorporation.

Copper‐Mediated Synthesis of (Diethylphosphono)difluoromethyl Thioethers from Diazonium Salts, NaSCN, and TMS‐CF2PO(OEt)2

AbstractAn expedient one‐pot synthesis of (diethylphosphono) difluoromethyl thioethers is described consisting of a Sandmeyer thiocyanation with in situ‐fluoroalkylation using TMS‐CF2PO(OEt)2 as the fluorine source. Both steps are mediated by copper(I) thiocyanate. The reaction is applicable to a wide range of functional groups, as demonstrated by 22 examples.

One-Pot Synthesis of Difluoromethyl Thioethers from Thiourea and Diethyl Bromodifluoromethylphosphonate.

A straightforward one-pot synthesis of difluoromethyl thioethers from thiourea and diethyl bromodifluoromethylphosphonate has been developed. Thiourea is a cheap and friendly sulfur reagent, while diethyl bromodifluoromethylphosphonate is a low-cost and stable difluorocarbene precursor. The strategy enabled the introduction of SCF2H moieties into indoles, pyrroles, and activated arenes and formed a number of difluoromethyl thioethers.

One-pot synthesis of (ethoxycarbonyl)difluoromethylthioethers from thiocyanate sodium and ethyl 2-(trimethylsilyl)-2,2-difluoroacetate (TMS-CF2CO2Et)

An efficient one-pot cascade methodology for the synthesis of (ethoxycarbonyl)difluoromethyl thioethers is described. Benzyl, allyl, alkyl halides or diazonium salts as the starting materials together with thiocyanate sodium and TMS-CF2CO2Et in the presence of CsF or NaOAc afford a variety of the fluoroalkylthiolated products in moderate to good yields.

Radical Difluororomethylation of Thiols with Difluoromethylphosphonium Triflate under Photoredox Catalysis.

A convenient, visible light-induced radical difluoromethylation of aryl-, heteroaryl-, and alkylthiols with difluoromethyltriphenylphosphonium triflate was developed to afford various difluoromethyl thioethers in moderate to excellent yields. The key reaction features include the use of a readily available CF2H radical source, mild reaction conditions, and excellent chemoselective thiol-difluoromethylation.

ChemInform Abstract: Synthesis of Aryl Tri‐ and Difluoromethyl Thioethers via a C—H‐Thiocyanation/Fluoroalkylation Cascade.

AbstractThe synthesis of aryl trifluoromethyl thioethers and aryl difluoromethyl thioethers proceed with remarkable regioselectivity for the most electron‐rich, sterically least hindered position of the arene.

Synthesis of aryl tri- and difluoromethyl thioethers via a C-H-thiocyanation/fluoroalkylation cascade.

An AlCl3 -catalyzed CH thiocyanation was discovered and combined with a Langlois-type trifluoromethylation to afford aryl trifluoromethyl thioethers directly from arenes, N-thiocyanatosuccinimide (NTS) and Ruppert-Prakash reagent. An analogous combination with a copper-mediated difluoromethylation gives access to aryl difluoromethyl thioethers. Both processes proceed with exceptional regioselectivity for the most electron-rich, sterically least hindered position of the arene. The sulfur and fluoroalkyl groups originate from different sources, so that the use of expensive, preformed fluoroalkylthiolation reagents is avoided.

ChemInform Abstract: Synthesis of Difluoromethyl Thioethers from Difluoromethyl Trimethylsilane and Organothiocyanates Generated in situ.

AbstractThe transformation of alkyl and (heteroaryl) thiocyanates to difluoromethyl thioethers is examined.

Synthesis of difluoromethyl thioethers from difluoromethyl trimethylsilane and organothiocyanates generated in situ.

A copper-CF2 H complex generated in situ from copper thiocyanate and TMSCF2 H smoothly converts organothiocyanates into valuable difluoromethyl thioethers. This reaction step can be combined with several thiocyanation methods to one-pot protocols, allowing late-stage difluoromethylthiolations of widely available alkyl halides and arenediazonium salts. This strategy enables the introduction of difluoromethylthio groups-a largely unexplored substituent with highly promising properties-into drug-like molecules.

Synthesis of Difluoromethyl Thioethers from Difluoromethyl Trimethylsilane and Organothiocyanates Generated In Situ

AbstractA copper‐CF2H complex generated in situ from copper thiocyanate and TMSCF2H smoothly converts organothiocyanates into valuable difluoromethyl thioethers. This reaction step can be combined with several thiocyanation methods to one‐pot protocols, allowing late‐stage difluoromethylthiolations of widely available alkyl halides and arenediazonium salts. This strategy enables the introduction of difluoromethylthio groups—a largely unexplored substituent with highly promising properties—into drug‐like molecules.