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The unprecedented use of CFSOCl for direct bifunctional chloro-trifluoromethylthiolation of alkenes and alkynes is reported. CFSCl, which is generated by the reduction of PPh, 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 CFHSOCl.

Trifluoromethanesulfinyl chloride (CF3SOCl) 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 CF3SOCl to CF3SO2Cl and CF3SCl provides two pathways for the trifluoromethylthiolation. Direct trifluoromethylthiolation with CF3SCl or trifluoromethylsulfoxidation with CF3SOCl is followed by reduction with CF3SOCl. This reagent can be used to functionalize benzothiophenes, benzofurans, and indenes under the promotion of Ag2CO3. 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 CF2HSOCl.

A highly carbon-selective monofluoromethylation of a broad range of β-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.Letter pubs.acs.org/OrgLett

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 SCFH moieties into indoles, pyrroles, and activated arenes and formed a number of difluoromethyl thioethers.

A one-pot difluoromethylthiolation of alkyl electrophiles with thiourea and diethyl bromodifluoromethylphosphonate is described. By changing the “H” source to most commonly used “D” source CD3OD and D2O, this strategy enables efficient synthesis of SCF2D-substituted molecules in good yields with high levels of D incorporation.

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.

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