The reaction of thiocarbonyl fluoride, generated from difluorocarbene, with various amines under mild conditions is described. Secondary amines, primary amines, and o‐phenylenediamines are converted ...to thiocarbamoyl fluorides, isothiocyanates, and difluoromethylthiolated heterocycles, respectively. Thiocarbamoyl fluorides were further transformed into trifluoromethylated amines by using a one‐pot process. Thiocarbonyl fluoride is generated in situ and is rapidly fully converted in one pot under mild conditions; therefore, no special safety precautions are needed.
Stay safe: The reaction of thiocarbonyl fluoride, generated from difluorocarbene, with various amines proceeded smoothly under mild conditions to give thiocarbamoyl fluorides, isothiocyanates, and difluoromethylthiolated heterocycles. Thiocarbonyl fluoride is generated in situ and no special safety precautions are needed.
Difluoromethylation is a straightforward and widely applied strategy used to incorporate HCF2 into organic molecules. In contrast, cyanation reagents are typically volatile or highly toxic, or they ...require harsh reaction conditions. Incorporation of both CN and HCF2 into organic molecules, such as alkenes, is a worthwhile but challenging task. A method for photocatalyzed cyanodifluoromethylation of alkenes has been developed, which employs a Ph3P+CF2CO2−/NaNH2 (or NH3) reagent system. Ph3P+CF2CO2− functions as both the HCF2 and CN carbon source. A cyanide anion is generated in situ under mild conditions, thereby avoiding the use of toxic cyanation reagents. The photocatalytic method permits cyanodifluoromethylation of a range of alkenes under mild room temperature conditions. The CN group within the products may be further derivatized by standard methods.
Photocatalyzed cyanodifluoromethylation of alkenes with a Ph3P+CF2CO2−/NaNH2 (or NH3) system is described. The use of toxic cyanation reagents can be avoided because Ph3P+CF2CO2− functions as both the HCF2 and CN carbon source to generate a range of HCF2‐ and CN‐containing products under mild conditions, which may be further derivatized.
The first trifluoromethylthiolation and 18Ftrifluoromethylthiolation 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 18FCF3S‐labeled molecules from most commonly used 18Ffluoride ions. The rapid radiochemical reaction time (≤1 min) and high functional‐group tolerance allow access to a variety of aliphatic 18FCF3S compounds in high yields.
18F label: An efficient, fast, and transition‐metal‐free protocol for trifluoromethylthiolation of alkyl electrophiles with in situ generated difluorocarbene in the presence of elemental sulfur and external fluoride ions is described. This strategy was applied to 18Ftrifluoromethylthiolation of alkyl electrophiles, which represents the first example of this type. Ts=4‐toluenesulfonyl.
The interconversion between difluoromethylene ylide and difluorocarbene is described. The difluoromethylene ylide precursor, Ph3P+CF2CO2−, could be turned into an efficient difluorocarbene reagent, ...whereas the classical difluorocarbene reagents, HCF2Cl and FSO2CF2CO2TMS, could generate highly reactive difluoromethylene ylide. Thus the Wittig difluoro‐olefination and difluorocyclopropanation could be selectively realized by using the same reagent. In addition, the ylides obtained from different carbene sources showed different reactivity in Wittig reactions.
Book of ylide: Difluoromethylene phosphonium ylide, generated from Ph3P+CF2CO2−, was turned into an efficient difluorocarbene reagent, whereas the classical difluorocarbene reagents, HCF2Cl and FSO2CF2CO2TMS, generated the highly reactive difluoromethylene ylide. Interestingly, it was found that the ylides obtained from different carbene sources showed different reactivity in Wittig reactions (see scheme; TMS=trimethylsilyl).
Trifluoromethyl substitution is notably popular in pharmaceuticals and agrochemicals; however, trifluoromethylated compounds normally rely on the use of cost-prohibitive or gaseous ...trifluoromethylating reagents, which diminishes the general applicability of these methods. Herein an efficient trifluoromethylation reagent trifluoromethylsulfonyl–pyridinium salt (TFSP) was reported, which can be readily prepared from cheap and easily available bulk industrial feedstocks. TFSP can generate a trifluoromethyl radical under photocatalysis and realize the effective azido- or cyano-trifluoromethylation reactions of alkenes.
As a versatile intermediate, difluorocarbene is an electron-deficient transient species, meaning that its oxidation would be challenging. Herein we show that the oxidation of difluorocarbene could ...occur smoothly to generate carbonyl fluoride. The oxidation process is confirmed by successful trifluoromethoxylation,
O-trifluoromethoxylation, the observation of AgOCF
species, and DFT calculations.
Depending on the nature of the attached functional moiety, the sulfonyl radical can either undergo an automatic SO2 liberation or react directly as the thermodynamically favored sulfonyl radical. ...Taking advantage of this unique property, we envisioned that through rational reaction design, the in situ release and re‐insertion of SO2, i. e., the shuttle of SO2, can be realized. Herein we report our recent progress in copper metallaphotoredox co‐catalyzed trifluoromethyl‐fluorosulfonylation of alkenes with TFSP as both the CF3 and SO2 source. Valuable functional groups are added across the double bonds. Besides, A wide array of synthetically useful moieties featuring distinct electronic patterns and various nitrogenous heterocycles are well tolerated by this strategy.
Organic phosphonium salts have served as important intermediates in synthetic chemistry. But the use of a substituent on the positive phosphorus as a nucleophile to construct C-C bond remains a ...significant challenge. Here we report an efficient transition-metal-free protocol for the direct nucleophilic arylation of carbonyls and imines with tetraarylphosphonium salts in the presence of caesium carbonate. The aryl nucleophile generated from phosphonium salt shows low basicity and good nucleophilicity, as evidenced by the successful conversion of enolizable aldehydes and ketones. The reaction is not particularly sensitive to water, shows wide substrate scope, and is compatible with a variety of functional groups including cyano and ester groups. Compared with the arylmetallic reagents that are usually moisture sensitive, the phosphonium salts are shelf-stable and can be easily handled.
A key intermediate, difluoromethylene phosphobetaine, in the Wittig reaction of ClCF2CO2Na-Ph3P with aldehydes was synthesized and characterized, which confirmed the reaction mechanism. The ...decarboxylation of this stable intermediate was a convenient approach for Wittig difluroolefination. Its reactivity could be adjusted by the modification of the substituent on the phosphorus.
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