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Ligand coupling on hypervalent main group elements has emerged as a pivotal methodology for the synthesis of functionalized N‐heteroaromatic compounds in recent years due to the avoidance of transition metals and the mildness of the reaction conditions. In this direction, the reaction of N‐heteroaryl sulfur(IV) and N‐heteroaryl phosphorus(V) compounds has been well studied. However, the ligand coupling of sulfur(VI) is still underdeveloped and the reaction of alkyl N‐heteroarylsulfones is still elusive, which does not match the high status of sulfones as the chemical chameleons in organic synthesis. Here we present a ligand coupling‐enabled formal SO2 extrusion of fluoroalkyl 2‐azaheteroarylsulfones under the promotion of Grignard reagents, which not only enriches the chemistry of sulfones, but also provides a novel and practical synthetic tool towards N‐heteroaromatic fluoroalkylation. [ABSTRACT FROM AUTHOR]

Radical fluoroalkylation of alkenes has been developed by electrochemical reduction of fluoroalkyl sulfones. A series of electron-deficient alkenes readily undergo hydrofluoroalkylation in good to excellent yields. This chemistry represents the first example of electrochemical generation of fluoroalkyl radicals from sulfones, which are used for practical radical fluoroalkylation of organic compounds. [ABSTRACT FROM AUTHOR]

A general method for the efficient difluoromethylation of alcohols using commercially available TMSCF2Br (TMS=trimethylsilyl) as a unique and practical difluorocarbene source is developed. This method allows primary, secondary, and even tertiary alkyl difluoromethyl ethers to be synthesized under weakly basic or acidic conditions. The reaction mainly proceeds through the direct interaction between a neutral alcohol and difluorocarbene, which is different from the difluoromethylation of phenols. Moreover, alcohols containing other moieties that are also reactive toward difluorocarbene can be transformed divergently by using TMSCF2Br. This research not only solves the synthetic problem of difluorocarbene-mediated difluoromethylation of alcohols, it also provides new insights into the different reaction mechanisms of alcohol difluoromethylation and phenol difluoromethylation with difluorocarbene species. [ABSTRACT FROM AUTHOR]

(Sulfonimidoyl)cyclopropanes have become the subject of special interest since they combine the advantages of two chemical leads (cyclopropane and sulfoximine). However, their synthesis is limited, and the stereoselective synthesis of optically enriched (sulfonimidoyl)cyclopropanes still remains an unsolved task. Here we report the first stereoselective (sulfonimidoyl)cyclopropanation reaction using α,β-unsaturated Weinreb amides and ( R)-PhSO(NTs)CH2Cl [( R)- 1]. This reaction possesses a broad substrate scope, and the products can be easily transformed into other useful cyclopropyl-containing and/or sulfonimidoyl-containing compounds. The Weinreb amide group and the counter cation of the base were found to be important for the selective C-Cl bond cleavage. [ABSTRACT FROM AUTHOR]

A AgF-mediated fluorination with a concomitant cross-coupling between a gem-difluoroolefin and a non-fluorinated olefin is reported. This highly efficient method provides facile access to both α-CF3 alkenes and β-CF3 ketones, which otherwise remain challenging to be directly prepared. The application of this method is further demonstrated by the synthesis of bioactive isoxazoline derivatives. This approach represents a conceptually novel route to trifluoromethylated compounds that combines the in situ generation of the CF3 moiety and a CH functionalization in a single reaction system. [ABSTRACT FROM AUTHOR]

Although many methods are available for the synthesis of optically enriched monofluoromethyl secondary alcohols, synthesizing optically enriched monofluoromethyl tertiary alcohols remains a challenge. An efficient and easy-to-handle nucleophilic fluoromethylation protocol was developed. The current monofluoromethylation showed much higher facial selectivity than the corresponding difluoromethylation and proceeded via a different type of transition state. Excellent stereoselective control at the fluorinated carbon chiral center was found, an effect believed to be facilitated by the dynamic kinetic resolution of the chiral α-fluoro carbanions. [ABSTRACT FROM AUTHOR]

Abstract: A new nucleophilic difluoromethylation chemistry using fluoride-induced (phenylsulfonyl)difluoromethylation with TMSCF2SO2Ph followed by the magnesium-metal-mediated desulfonylation has been achieved. This methodology is compatible with both enolizable and non-enolizable aldehydes and ketones and has special advantage in the case of enolizable aldehydes. The new efficient desulfonylation method is considered to be environmentally benign due to the absence of mercury. [Copyright &y& Elsevier]

Abstract: CH2ClF has been found to be a useful electrophilic monofluoromethylating agent for a variety of O-, S-, and N-nucleophiles. The reaction is not sensitive to the radical scavenger such as nitrobenzene, which strongly supports an SN2 mechanism rather than an SET mechanism. Although most of these products (fluoromethyl ethers, sulfides, and amines) can be isolated with good purity, some of these compounds do intend to decompose (via defluorination) during storage. The electrophilic monofluoromethylation of carbon-nucleophiles was attempted with CH2ClF, CH2FI, or FCH2OTs as monofluoromethylating agents, but with no success. [Copyright &y& Elsevier]

Abstract: 1,1-Difluoroethysilanes (R3SiCF2CH3, R=Me or Et) were synthesized from 1,1-difluoroethyl phenyl sulfone and chlorosilanes using magnesium metal via reductive 1,1-difluoroethylation. It was confirmed that 1,1-difluoroethylsilanes were effective 1,1-difluoroethylating reagents for carbonyl compounds. [Copyright &y& Elsevier]

Abstract: 1-Aryl-2,2-difluoro enol benzoates 4 has been prepared from α-(phenylsulfonyl)-difluoromethylated benzoates 3, which can be readily obtained from the reactions between simple aldehydes and PhSO2CF2H (or TMSCF2SO2Ph). 2,2-Difluoro enol esters 4 are relatively more stable compounds than 2,2-difluoro enol sily ethers, and they promise to act as interesting fluorinated building blocks for further elaborations. [Copyright &y& Elsevier]

Abstract: Tetrakis(dimethylamino)ethylene (TDAE) was found to be an effective electron-transfer agent that promoted the reactions of bromodifluoromethyl phenyl sulfone with aldehydes to give structurally diverse (benzenesulfonyl)difluoromethylated alcohols in good yield, which can be further transformed into difluoromethyl alcohols and 1,1-difluoro-1-alkenes via reductive desulfonylation and Julia olefination, respectively. [Copyright &y& Elsevier]

Cesium carbonate (Cs 2 CO 3 )-mediated decarboxylative fluorination of β -ketoacids using NFSI in the MeCN/H 2 O mixed solvent system affords α-fluoroketones with a broad scope. Both electron-rich and electron-deficient α-non-substituted β -ketoacids are amenable to this protocol. The mechanistic study indicates that the reaction proceeds through electrophilic fluorination followed by decarboxylation, which is different from the decarboxylative fluorination of normal carboxylic acids. [ABSTRACT FROM AUTHOR]

Abstract: A facile synthesis of anti-α-(difluoromethyl)-β-amino alcohols was accomplished by using a nucleophilic difluoromethylation strategy with Me3SiCF2SO2Ph reagent. Good to excellent chemical yields as well as modest to good diastereoselectivity were achieved in these reactions. We found that the solvent played a crucial role in controlling the diastereoselectivity of the reaction, and an apolar solvent such as toluene helps to improve the diastereoselectivity of the reaction. The anti-α-(difluoromethyl)-β-amino alcohol 3a was demonstrated to be a useful synthetic intermediate to synthesize difluoromethylated oxazolidinone 9. [Copyright &y& Elsevier]

Abstract: We have successfully achieved nucleophilic (phenylsulfinyl)difluoromethylation of both enolizable and non-enolizable aldehydes and ketones by using difluoromethyl phenyl sulfone (1) as the fluoroalkylating agent. Although the chemical yields of the reactions are good to excellent, the observed diastereoselectivity is poor (dr=1:1.04–2.03). The present synthetic methodology provides a convenient alternative for the preparation of α-(phenylsulfinyl)difluoromethylated carbinols that were previously synthesized via a two-step procedure. [Copyright &y& Elsevier]

Abstract: A new solid acid/superacid catalyzed microwave assisted synthesis of trifluoromethyl-imines is described. Various α,α,α-trifluoromethylketones react readily with primary amines to produce the corresponding imines. Two different strategies have been employed; one is the application of microwave irradiation coupled with solvent-free solid acid catalysis. The other method, for highly deactivated substrates includes the use of a pressure vessel at 175°C temperature, with solid superacid catalysis. Using the solid acid K-10 montmorillonite or the superacidic perfluorinated resinsulfonic acid Nafion-H, a wide variety of trifluoromethylated imines have been synthesized using the above methods. The products have been isolated in good to excellent yields and high selectivities. This new environmentally friendly synthetic methodology provides significantly higher yields than traditional methods during relatively short reaction times for the preparation of the target compounds. [Copyright &y& Elsevier]

Abstract: Both secondary and tertiary difluoromethylated carbinols were found to readily react with acetonitrile under the catalysis of concentrated sulfuric acid to give the corresponding difluoromethylated acetamides in good yields, which is remarkably more efficient than the previously reported Ritter reactions with corresponding trifluoromethylated carbinols. Similarly, monofluoromethylated and (benzenesulfonyl)difluoromethylated carbinols have shown good reactivity in the Ritter reactions. Since the acetamides can be mildly deacetylated to give amines, the present methodology provides a convenient way for the synthesis of both difluoromethyl- and monofluoromethyl-containing amines starting from simple carbonyl compounds. [Copyright &y& Elsevier]

A novel Cu-catalyzed gem-difluoroolefination of diazo compounds is described. [ABSTRACT FROM AUTHOR]