2251-82-3

Upstream product

• 402-43-7 p-trifluoromethylphenyl bromide 
• 214360-65-3 4-trifluoromethylphenylboronic acid pinacol ester 
• 56228-54-7 2-((difluoromethyl)sulfonyl)-4,6-dimethylpyrimidine 
• 2925-22-6 2,2-difluoroacetyl fluoride 
• 501374-30-7 5,5-dimethyl-2-(4-trifluoromethyl-phenyl)-[1,3,2]dioxaborinane 
• 73789-96-5 ethyl α,α-difluoro-4-(trifluoromethyl)benzeneacetate 
• 1493-03-4 iododifluoromethane 
• 402-51-7 4-(trifluoromethyl)phenylmagnesium bromide 
• 65864-64-4 trimethyl(difluoromethyl)silane 
• 98-56-6 4-chlorobenzotrifluoride 
• 1511-62-2 bromodifluoromethane 
• 75-10-5 Difluoromethane 
• 115262-01-6 [bromo(difluoro)methyl]-trimethyl-silane 
• 858344-44-2 bis[4-(trifluoromethyl)phenyl]zinc 

Downstream Products

• 433-19-2 1,4-bis(trifluoromethyl)benzene 
• 114467-78-6 1-(Difluoro-phenylsulfanyl-methyl)-4-trifluoromethyl-benzene 
• 114467-82-2 1-(Difluoro-phenoxy-methyl)-4-trifluoromethyl-benzene 
• 114467-87-7 1-(Azido-difluoro-methyl)-4-trifluoromethyl-benzene 
• 2251-60-7 1-(bromodifluoromethyl)-4-(trifluoromethyl)benzene 

Relevant academic research and scientific papers

Decarbonylative Fluoroalkylation at Palladium(II): From Fundamental Organometallic Studies to Catalysis

This Article describes the development of a decarbonylative Pd-catalyzed aryl-fluoroalkyl bond-forming reaction that couples fluoroalkylcarboxylic acid-derived electrophiles [RFC(O)X] with aryl organometallics (Ar-M′). This reaction was optimized by interrogating the individual steps of the catalytic cycle (oxidative addition, carbonyl de-insertion, transmetalation, and reductive elimination) to identify a compatible pair of coupling partners and an appropriate Pd catalyst. These stoichiometric organometallic studies revealed several critical elements for reaction design. First, uncatalyzed background reactions between RFC(O)X and Ar-M′ can be avoided by using M′ = boronate ester. Second, carbonyl de-insertion and Ar-RF reductive elimination are the two slowest steps of the catalytic cycle when RF = CF3. Both steps are dramatically accelerated upon changing to RF = CHF2. Computational studies reveal that a favorable F2C-H - -X interaction contributes to accelerating carbonyl de-insertion in this system. Finally, transmetalation is slow with X = difluoroacetate but fast with X = F. Ultimately, these studies enabled the development of an (SPhos)Pd-catalyzed decarbonylative difluoromethylation of aryl neopentylglycol boronate esters with difluoroacetyl fluoride.

Iron-Catalyzed Fluoroalkylation of Arylborates with Sulfone Reagents: Beyond the Limitation of Reduction Potential

The iron-catalyzed alkyl–aryl coupling reaction between sulfones and arylboron compounds has remained a challenge. We report the first iron-catalyzed radical difluoroalkylation of arylborates with N-heteroaryl sulfones. The coordination between the iron catalyst and the nitrogen atom of N-heteroaryl sulfones was identified to be important in overcoming the reduction potential limitation of sulfones in the intermolecular single-electron-transfer process, which enables both fluoroalkyl N-heteroaryl sulfones (with relatively high reduction potentials) and nonfluorinated alkyl N-heteroaryl sulfones (with low reduction potentials) to serve as powerful alkylation reagents.

Controlling the cleavage of carbon-carbon bonds to generate α,α-difluorobenzyl carbanions for the construction of difluoromethylbenzenes

Controlling the cleavage of carbon-carbon bonds during a chemical reaction is a substantial challenge; however, synthetic methods that accomplish this objective produce valuable and often unexplored reactivity. We have designed a mild process to generate α,α-difluorobenzyl carbanions in the presence of potassium carbonate by exploiting the cleavage of C-C bonds during the release of trifluoroacetate. The initiating reagent is potassium carbonate, which represents an improvement over existing protocols that require a strong base. Fragmentation studies across substituted arenes and heteroarenes were conducted along with computational analyses to elucidate reactivity trends. Furthermore, the mildly generated α,α-difluorobenzyl carbanions from electron-deficient aromatics and heteroaromatic rings can react with aldehydes to create derivatives of difluoromethylbenzenes, which are valuable synthetic targets.

Difluoromethyl-substituted compound (by machine translation)

[Problem] to provide a, simple and inexpensive manufacturing method is difluoromethyl substituted compounds using a reagent. [Solution] a method for producing a compound using a catalyst [...] difluoromethyl-substituted,(I) the catalyst, a nickel compound and nitrogen in the bidentate ligand, raw Ar a-Z " in the formula, the Ar, substituted or unsubstituted aryl group or a substituted or unsubstituted 5 - 10 membered heteroaryl group C6 a-14, Z is, (OR) B2 Or a group represented by a is represented MgX. " Compound represented, difluoromethyl-substituted compounds, Ar e CF2 A method for producing a compound represented by H, or(II) catalyst, a palladium compound and a diphosphine ligand, raw material is Q-a B (OR1 )2 " In the formula, Q is, substituted or unsubstituted aryl C6 a-10, 5 - 10 membered heteroaryl or substituted or unsubstituted, or Ar1 A group represented by - CH=CH - shown. R1 Is, a hydrogen atom or an alkyl group C1 a-6. " Compounds, a compound represented by Q-a Zn-to-Q or, difluoromethyl-substituted compounds, Q-to-CF2 A method for producing a compound represented by H. [Drawing] no (by machine translation)

Ligand-Less Iron-Catalyzed Aromatic Cross-Coupling Difluoromethylation of Grignard Reagents with Difluoroiodomethane

Iron-catalyzed cross-coupling difluoromethylations of the Grignard reagents with difluoroiodomethane provide various aromatic difluoromethyl products in good yields, not employing sterically demanding ligands. Difluoromethylations proceed within 30 min at -20 °C with 2.0 equiv of the Grignard reagents and FeCl3 or Fe(acac)3 (2.5 mol %). Mechanistic investigations clarify difluoromethyl radical intervention; Fe(0) ate is initially generated. Single-electron transfer from Fe(0) ate to difluoroiodomethane takes place. Recombination with aryl groups gives Ar-CF2Hs. The catalyst can be regenerated by the Grignard reagents.

Palladium-Catalyzed Difluoromethylation of Aryl Chlorides and Bromides with TMSCF2H

A palladium-catalyzed cross-coupling of aryl chlorides/bromides with TMSCF2H is described. Two different catalysts, Pd(dba)2/BrettPhos and Pd(PtBu3)2, are demonstrated and provide a variety of difluoromethylated arenes in good yields.

Metallaphotoredox Difluoromethylation of Aryl Bromides

Herein, we report a convenient and broadly applicable strategy for the difluoromethylation of aryl bromides by metallaphotoredox catalysis. Bromodifluoromethane, a simple and commercially available alkyl halide, is harnessed as an effective source of difluoromethyl radical by silyl-radical-mediated halogen abstraction. The merger of this fluoroalkyl electrophile activation pathway with a dual nickel/photoredox catalytic platform enables the difluoromethylation of a diverse array of aryl and heteroaryl bromides under mild conditions. The utility of this procedure is showcased in the late-stage functionalization of several drug analogues.

Nickel-Catalyzed Aromatic Cross-Coupling Difluoromethylation of Grignard Reagents with Difluoroiodomethane

The nickel-catalyzed cross-coupling difluoromethylation of the Grignard reagents with difluoroiodomethane is shown to provide the corresponding aromatic difluoromethyl products in excellent to moderate yields. The difluoromethylation proceeds smoothly within 1 h at room temperature with 1.5 equiv of the Grignard reagents in the presence of Ni(cod)2/TMEDA (2.5-0.5 mol %). Mechanistic studies clarify that the oxidative addition of the Ni(0) catalyst to difluoroiodomethane provides the TMEDA-Ni(II)(CF2H)I complex. This intermediate is transformed to TMEDA-Ni(II)(CF2H)Ph via transmetalation with PhMgBr. The reductive elimination takes place to give the aromatic cross-coupling difluoromethylation product along with regeneration of the TMEDA-Ni(0) catalyst. Electron paramagnetic resonance (EPR) and radical clock analyses of the nickel-catalyzed reaction provide no EPR active Ni(I) and Ni(III) species at around g = 2 and only a trace amount of the cyclization product.

Bulky Diamine Ligand Promotes Cross-Coupling of Difluoroalkyl Bromides by Iron Catalysis

Although iron-catalyzed cross-coupling of Grignard reagents with alkyl halides has been well established, the adoption of the reaction for fluoroalkylations has not been reported because traditional catalytic systems often lead to defluorination reactions. Described herein is the investigation of an iron-catalyzed cross-coupling between arylmagnesium bromides and difluoroalkyl bromides with modified N,N,N′,N′-tetramethyl-ethane-1,2-diamine (TMEDA) as a ligand. The use of this bulky diamine, in which a butylene is substituted at one carbon atom of the ethylene backbone in TMEDA, enables the iron-catalyzed difluoroalkylation under mild reaction conditions with a wide range of difluoroalkyl bromides, including vulnerable bromodifluoromethane, thus providing a general and cost-efficient route for applications in medicinal chemistry.

Iron-Catalyzed Difluoromethylation of Arylzincs with Difluoromethyl 2-Pyridyl Sulfone

We report the first iron-catalyzed difluoromethylation of arylzincs with difluoromethyl 2-pyridyl sulfone via selective C-S bond cleavage. This method employs the readily available, bench-stable fluoroalkyl sulfone reagent and inexpensive iron catalyst, allowing facile access to structurally diverse difluoromethylated arenes at low temperatures. The experiment employing a radical clock indicates the involvement of radical species in this iron-catalyzed difluoromethylation process.