Synthesis of Diaryl Tellurides with Sodium Aryltellurites under Mild Conditions.

A highly efficient new protocol has been developed for the formation of C-Te bonds, leading to both symmetrical and unsymmetrical diaryl tellurides. This protocol utilizes sodium aryltellurites (4), which can be easily prepared from low-cost aryltelluride trichlorides and NaOH. The synthesis involves the use of 4 and arylazo sulfones as starting materials in the presence of (MeO)2P(O)H. A variety of diaryl tellurides are obtained in moderate to good yields using this method. Importantly, this innovative protocol eliminates the need for traditional, highly toxic aryltellurolating reagents such as diaryl ditellurides and elemental tellurium. This study will bring new vitality to the synthesis of tellurides.

Synthesis of N-Difluoromethyl Carbonyl Compounds from N-Difluoromethylcarbamoyl Fluorides.

Fluorinated small molecules are commonly used in functional small-molecule chemistry, and N-difluoromethyl (N-CF2H) compounds are particularly intriguing due to their unique and unexplored physiochemical properties. However, despite limited progress, a general methodological approach to the synthesis of N-CF2H compounds remains elusive. Here, guided by computation, we present a simple and practical protocol to access N-CF2H amides and related carbonyl derivatives. The protocol involves a one-pot conversion of thioformamides through desulfurization-fluorination and acylation, providing N-difluoromethylcarbamoyl fluoride building blocks that can be further diversified to a variety of unexplored N-CF2H carbonyl compounds with rich functionality. Additionally, preliminary studies on their properties and stability showcased their potential application in pharmaceuticals and agrochemicals.

Synergistic Effect of Squaric Acid in Bromine-Catalyzed Deoxygenation of Sulfonyl Derivatives: Mechanistic Investigations and Synthetic Applications in Electrophilic (Fluoroalkyl)sulfenylation.

A method for electrophilic (fluoroalkyl)sulfenylation of nucleophiles by collaborative CTAB- and squaric acid-promoted deoxygenation of sulfonyl derivatives is reported. Mechanistic studies indicate that squaric acid dramatically decreased the energy barrier in the first step of deoxygenation. The mild deoxygenation process enables the reduction of a wide range of functionalized sulfonyl chlorides as well as sulfonic anhydrides. The novel method represents an operationally simple protocol using readily available reagents and exhibits broad functional group tolerance.

Synthesis of Thiocarbamoyl Fluorides and Isothiocyanates Using Amines with CF3SO2Cl.

A practical and efficient method to synthesize thiocarbamyl fluorides and isothiocyanates from amines with trifluoromethanesulfonyl chloride was developed. In the presence of the reducing agent triphenylphosphine and sodium iodide, thiocarbamyl fluorides and isothiocyanates were synthesized from secondary/primary amine in moderate to excellent yields, respectively. A broad scope of substrates and good functional group compatibility were observed.

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.

Fluoromethoxymethylation of Nitrogen Heterocyclic Compounds with Fluoromethyl Iodide.

The fluoromethoxymethylation of nitrogen heterocyclic compounds with fluoromethyl iodide has been reported for the first time. In this reaction, a number of unexplored fluoromethoxymethylated nitrogen heterocyclic compounds including indoles, carbazoles, and 1H-indazoles were efficiently formed. Mechanistic studies indicated that this transformation consists of electrophilic monofluoromethylation, rapid hydrolysis, and another electrophilic monofluoromethylation. This method makes it possible to synthesize complex bioactive molecules containing a CH2OCH2F group, which have the potential to be a new series of fluorine-containing chemical entities for medicinal chemists.

Regioselective Chlorothiolation of Alkenes with Sulfonyl Chlorides.

Newly developed sulfonyl chloride-based regioselective chlorothiolation of alkenes has been disclosed; the reaction is compatible with a variety of functional groups and can be scaled up to the gram scale with no loss in yield. The employment of readily available reactants, mild reaction conditions, and high regioselectivity makes this process very practical. Mechanistic studies revealed a possible free radical reaction pathway.

One-pot synthesis of trifluoromethyl amines and perfluoroalkyl amines with CF3SO2Na and RfSO2Na.

A newly developed CF3SO2Na-based trifluoromethylation of secondary amines has been disclosed, and the method has been successfully extended to the configuration of perfluoroalkyl amines using RfSO2Na, complementing the established synthesis strategy of trifluoromethyl amines. Advantages of the method include good functional group tolerance, mild conditions, and inexpensive or easy-to-handle materials. Mechanistic probes indicate that the thiocarbonyl fluoride formed in situ is the key intermediate in the reaction.

Highly Carbon-Selective Monofluoromethylation of ß-Ketoesters with Fluoromethyl Iodide.

A highly carbon-selective monofluoromethylation of a broad range of ß-ketoesters with fluoromethyl iodide under mild conditions is described. The uses of lithium tert-butoxide as the base and diglyme as the solvent made great contributions to the high C/O regioselectivity.

Copper-Catalyzed Vicinal Chloro-thiolation of Alkynes with Sulfonyl Chlorides.

A copper-catalyzed vicinal chloro-thiolation of alkynes with inexpensive and diversified sulfonyl chlorides RSO2Cl (R = aryl, alkyl) has been developed. This practical and scalable reaction could be used for the construction of a number of unexplored bioactive chlorothiolated alkenes. Internal alkynes could also undergo the chloro-thiolation to provide tetrasubstituted alkynes. Preliminary mechanistic investigations revealed a plausible radical process involving a sulfur-centered radical intermediate via copper-mediated homolysis of the S-Cl bond.

Trifluoromethanesulfinyl Chloride for Electrophilic Trifluoromethythiolation and Bifunctional Chlorotrifluoromethythiolation.

Trifluoromethanesulfinyl chloride (CF3 SOCl) has been introduced as a new reagent for C-H trifluoromethylthiolation of indoles, thiophenes, and ketones under catalyst-free conditions and in the absence of reductant. The disproportionation of CF3 SOCl to CF3 SO2 Cl and CF3 SCl provides two pathways for the trifluoromethylthiolation. Direct trifluoromethylthiolation with CF3 SCl or trifluoromethylsulfoxidation with CF3 SOCl is followed by reduction with CF3 SOCl. This reagent can be used to functionalize benzothiophenes, benzofurans, and indenes under the promotion of Ag2 CO3 . It can also be used for trifluoromethylthiolation of thiols and benzeneselenols, and 1,2-bifunctional chlorotrifluoromethylthiolation of indoles, styrenes, and alkyenes. The method can also be extended for difluorometylthiolation reactions using CF2 HSOCl.

Bunte Salt CH2FSSO3Na: An Efficient and Odorless Reagent for Monofluoromethylthiolation.

A practical and efficient monofluoromethylthiolation that employs the typical Bunte salt, sodium S-(fluoromethyl) sulfurothioate, as the sulfur source is described. This reagent reacts readily with a variety of aryl amines and aryl thiols. The high tolerance of functional groups demonstrates the potential of this reaction. In addition, this method is suitable for the late-stage monofluoromethylthiolation of complex bioactive molecules.

Metal-Free Electrophilic Trifluoroethylthiolation with NaSO2CH2CF3.

Metal-free trifluoroethylthiolation with fluorinated sulfinate salt NaSO2CH2CF3 under reductive conditions has been developed. The strategy enables the installation of the SCH2CF3 moiety efficiently to form a number of unexplored stable trifluoroethylthiolated heterocycles, arenes, and thiols, which have the potential to be a new series of fluorine-containing chemical entities for medicinal chemists.

Fluoroalkylsulfonyl Chlorides Promoted Vicinal Chloro-fluoroalkylthiolation of Alkenes and Alkynes.

The unprecedented use of CF3SO2Cl for direct bifunctional chloro-trifluoromethylthiolation of alkenes and alkynes is reported. CF3SCl, which is generated by the reduction of PPh3, undergoes electrophilic addition and then chlorination to give the bifunctionalized products without using an additional chlorine source. The method is also applicable for chloro-difluoromethylthiolation using CF2HSO2Cl.

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.

Direct Trifluoromethylthiolation and Perfluoroalkylthiolation of C(sp(2))-H Bonds with CF3SO2Na and RfSO2Na.

A new method for CF3SO2Na-based direct trifluoromethylthiolation of C(sp(2))-H bonds has been developed. CF3SSCF3 is generated in situ from cheap and easy-to-handle CF3SO2Na, and in the presence of CuCl can be used for electrophilic trifluoromethylthiolation of indoles, pyrroles, and enamines. The method has been extended to perfluoroalkylthiolation reactions using RfSO2Na.