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The difluoromethylation of N-arylsulfonyl hydrazones with difluorocarbene generated from difluoromethylene phosphobetaine (Ph3P+CF2CO2−) to give various difluoromethyl aryl sulfones is described.

Phosphonium salt ([Ph3P(+)CF2H] Br(-), DFPB) was found to be an efficient nucleophilic difluoromethylation reagent. Although DFPB is known as a phosphonium ylide precursor, its reaction with carbonyl compounds under traditional "Wittig reaction conditions" did not give the expected Wittig difluoroolefinated products, but afforded the nucleophilic difluoromethylation products, α-CF2H alcohols. Mechanistic investigation reveals that the unexpected transformation proceeded via the direct transfer of the CF2H group, which resulted from the high P-O affinity.

The hydroperfluoroalkylation of electron-deficient olefins with perfluoroalkyl iodides promoted by a zinc/viologen system is described. Interestingly, no iodoperfluoroalkylation product was observed without the presence of radical H-donor.

DBU-promoted trifluoromethylation of aryl iodides with difluoromethyltriphenylphosphonium bromide (DFPB) in the presence of copper source is described. In this transformation, DBU not only acts as base to deprotonate the difluoromethyl group in DFPB to generate difluoromethylene phosphonium ylide Ph3P+CF2−, but also converts the difluorocarbene generated from ylide Ph3P+CF2− into trifluoromethyl anion, finally resulting in the trifluoromethylation of aryl iodides. The reactions proceeded smoothly to afford expected products in moderate to good yields.

The trifluoromethylcarbene (:CHCF3) was found to be conveniently generated from (2,2,2-trifluoroethyl)diphenyl-sulfonium triflate (Ph2S+CH2CF3 –OTf), which was successfully applied in Fe-catalyzed cyclopropanation of olefins, giving the corresponding trifluoromethylated cyclopropanes in high yields.

The O-difluoromethylation of 1,3-diones with S-difluoromethyl sulfonium salt is described. The sulfonium salt was previously believed to be a direct difluoromethylation reagent, but our mechanistic investigation reveals that the O-difluoromethylation reaction proceeds not only via the direct transfer of the CF2H group, but also via a difluorocarbene process. This work represents the first protocol for mild O-difluoromethylation of acyclic 1,3-diones.

Cross-coupling between difluorocarbene and carbene-derived intermediates generated from diazocompounds was developed to give gem-difluoroolefins, which constitutes a fast practical pathway to achieve hindered gem-difluoroolefins. The cross-coupling between difluorocarbene and aryl diazoacetates proceeded smoothly in the presence of a copper source, whereas its coupling with diaryl diazomethanes occurred well under metal-free conditions. A mechanism involving a copper–difluorocarbene complex was proposed.

(2,2,2-Trifluoroethyl)diphenylsulfonium triflate was found to be an efficient ylide reagent for the Johnson–Corey–Chaykovsky reaction to afford trifluoromethyl epoxides, cyclopropanes and aziridines. Interestingly, excellent but different diastereoselectivity was observed for these transformations. Both trifluoromethyl epoxides and cyclopropanes were obtained with trans-selectivity, whereas aziridines were obtained with cis-selectivity.

Difluoromethylene phosphobetaine (PDFA, II) is found to be an efficient difluorocarbene precursor in the difluoromethylation of the activated X—H bonds (X = N, O, S), aliphatic thiols (IV), and gem-difluorocyclopropenation of alkynes.

AuI/CuI-co-catalyzed tandem 1,3-acyloxy migration/trifluoromethylation reaction of propargyl esters to give α-trifluoromethyl enones in moderate yields and with excellent stereoselectivity is described. It is proposed that the reaction proceeds through the 1,3-acyloxy migration of the propargyl esters catalyzed by AuI to produce an allenic intermediate, followed by its trifluoromethylation to give the final product.

Difluoromethylene phosphobetaine (Ph3P+CF2CO2−, PDFA), a known difluorocarbene reagent, was found to be able to efficiently trifluoromethylate terminal alkynes in the presence of Cu(I) and potassium fluoride. The transformation proceeded smoothly to afford the corresponding trifluoromethylated acetylenes in moderate yields.

The past decade has witnessed the significant advances of asymmetric organocatalytic fluorination, monofluoroalkylation, gem-difluoroalkylation, and trifluoromethylation. This digest summarizes the latest progress of these reactions. In the research area of asymmetric organocatalytic fluorination, a new catalysis concept, chiral anion phase-transfer catalysis strategy, has emerged and has proved to be highly efficient. Asymmetric organocatalytic monofluoroalkylation and gem-difluoroalkylation have been much less explored and the Lewis base/acid catalysis has been the most used strategy. Compared with electrophilic trifluoromethylation, nucleophilic trifluoromethylation has been intensively studied in the research field of asymmetric organocatalytic trifluoromethylation. (C) 2014 Published by Elsevier Ltd.

A copper-mediated trifluoromethylation of propargyl acetates with S-(trifluoromethyl)diphenylsulfonium triflate leading to trifluoromethylated allenes in moderate to excellent yields is described.

The decarboxylation of potassium 2-pyridinyl sulfonyldifluoroacetate and its subsequent reaction with aldehydes was found to be an efficient approach for the Julia–Kocienski reaction under mild conditions to give gem-difluoro olefins in moderate to excellent yields. Owing to its high stability in the pure state and its easy decarboxylation in polar solvents, potassium 2-pyridinyl sulfonyldifluoroacetate is expected to be an efficient gem-difluoro-olefination reagent.

We have developed an efficient method to achieve N-gem-difluorocyclopropylation of N-heterocycles with the use of gem-difluorocyclopropyl tosylate as a building block under mild conditions. gem-Difluorocyclopropyl tosylates could be easily prepared on a large scale and exhibit great stability.

The presented strategy offers a straightforward access to beta-halodifluoromethyl substituted ketones which are difficult to prepare using other methods.

The conversion of the difluoromethylene ylide precursor (II) to difluorocarbene is studied to enable the synthesis of difluorocyclopropenes (III) or the difluoromethyl substituted compounds (V), (VII) and (IX).

The CF3SO3H-promoted ring opening of gem-difluorocyclopropyl ketones prefers to undergo proximal bond cleavage and the subsequent cyclization with nitriles occurred smoothly to give 2-fluoropyrroles.

S-(Trifluoromethyl)diarylsulfonium triflate is described as reagent for the Cu-mediated reaction with terminal alkynes to give trifluoromethylated alkynes (III) generally in good yields

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.

CF3- or –CF2-containing tetrahydroquinolines have been asymmetrically synthesized from the reaction of fluorinated N-arylimines with benzyl N-vinylcarbamate in the presence of a chiral phosphoric acid.

Title reaction proceeds with excellent regioselectivity at the C(sp2) atom adjacent to the fluoroalkyl group.

Water was found to be a suitable reaction medium for the direct asymmetric aldol reaction of various cyclic ketones with aryl aldehydes catalyzed by a primary-tertiary diamine-Bronsted acid.

A series of pyrrolidinium-based salts with new fluorine-containing anions were synthesized. Different melting points could be obtained by changing the length of the fluoroalkyl chain of the anions. The pyrrolidinium 1,1,2,2-tetrafluoro-2-(1,1,2,2-tetrafluoroethoxy)ethanesulfonate ([C 4 H 8 NH 2 ][H(CF 2 ) 4 O(CF 2 ) 2 SO 3 ]) is highly fluid even below room temperature. It can be used both as a recyclable solvent and as an efficient catalyst for Friedel–Crafts alkylations of indoles with nitroalkenes.

An efficient method was developed for the synthesis of pentafluoroiodoethane from chloropentafluoroethane. Sulfinatodechlorination of CF3CF2Cl was carefully investigated. Subsequent iodination can be conducted in one pot without further purification, giving the corresponding CF3CF2I in practically acceptable yield.