343957-95-9

Upstream product

• 1511-62-2 bromodifluoromethane 
• 17878-43-2 [4-(trimethylsilyl)phenyl]magnesium bromide 
• 65094-22-6 diethyl (bromodifluoromethyl)phosphonate 
• 17865-11-1 (4-(trimethylsilyl)phenyl)boronic acid 
• 2199-32-8 4-trimethylsilylbenzaldehyde 
• 1493-03-4 iododifluoromethane 
• 75-45-6 Chlorodifluoromethane 
• 667-27-6 Ethyl bromodifluoroacetate 

Relevant academic research and scientific papers

Controllable catalytic difluorocarbene transfer enables access to diversified fluoroalkylated arenes

Difluorocarbene has important applications in pharmaceuticals, agrochemicals and materials, but all these applications proceed using just a few types of reaction by taking advantage of its intrinsic electrophilicity. Here, we report a palladium-catalysed strategy that confers the formed palladium difluorocarbene (Pd=CF2) species with both nucleophilicity and electrophilicity by switching the valence state of the palladium centre (Pd(0) and Pd(ii), respectively). Controllable catalytic difluorocarbene transfer occurs between readily available arylboronic acids and the difluorocarbene precursor diethyl bromodifluoromethylphosphonate (BrCF2PO(OEt)2). From just this simple fluorine source, difluorocarbene transfer enables access to four types of product: difluoromethylated and tetrafluoroethylated arenes and their corresponding fluoroalkylated ketones. The transfer can also be applied to the modification of pharmaceuticals and agrochemicals as well as the one-pot diversified synthesis of fluorinated compounds. Mechanistic and computational studies consistently reveal that competition between nucleophilic and electrophilic palladium difluorocarbene ([Pd]=CF2) is the key factor controlling the catalytic difluorocarbene transfer.

A fluorine-containing methyl compounds and its preparation method (by machine translation)

The invention discloses a fluorine-containing methyl compounds and its preparation method. The invention provides a fluorine-containing shown as formula C methyl compounds, wherein R is aryl group containing, or, containing a hetero aryl group, and the aryl group or the heteroaryl on the aromatic carbon atom and CFm Hn Connected, m is 1 or 2, m + n=3. The compounds according to the prior art is difficult to make, the preparation method of the raw material and the catalyst are the ordinary industrial raw materials, cheap and easy to obtain, high reaction efficiency, high yield, after treatment is simple, low toxicity, environmental protection, functional group compatibility is good, broad-spectrum is strong, the production cost is low, it has very good market application prospect. (by machine translation)

Accessing Difluoromethylated and Trifluoromethylated cis-Cycloalkanes and Saturated Heterocycles: Preferential Hydrogen Addition to the Substitution Sites for Dearomatization

Reported here is a straightforward process in which a cyclic (alkyl)(amino)carbene/Rh catalyst system facilitates the preferential addition of hydrogen to the substitution sites of difluoromethylated and trifluoromethylated arenes and heteroarenes, leading to dearomative reduction. This strategy enables the diastereoselective synthesis of cis-difluoromethylated and cis-trifluoromethylated cycloalkanes and saturated heterocycles, and even allows formation of all-cis multi-trifluoromethylated cyclic products with a defined equatorial orientation of the di- and trifluoromethyl groups. Deuterium-labeling studies indicate that hydrogen preferentially attacks the substitution sites of planar arenes, resulting in dearomatization, possibly with heterogeneous Rh as the reactive species, followed by either reversible or irreversible hydrogen addition to the nonsubstitution sites.

Precatalyst Effects on Pd-Catalyzed Cross-Coupling Difluoromethylation of Aryl Boronic Acids

The Pd-catalyzed difluoromethylation of aryl boronic acids with difluoroiodomethane is shown to provide the difluoromethyl compounds in high to moderate yields by Pd(PPh3)2/DPEphos catalyst in H2O/toluene. Mechanistic studies show that the oxidative addition by Pd(PPh3)4 rather than Pd2(dba)3 precatalyst to difluoroiodomethane provides a square-planar trans-(PPh3)2Pd(II)(CF2H)I complex defined by X-ray crystallographic analysis. The trans-(PPh3)2Pd(CF2H)I complex is transformed to cis-(PPh3)2Pd(CF2H)Ph detected by low temperature NMR analysis, via transmetalation with phenylboronic acids. The reductive elimination occurs via ligand exchange to DPEphosPd(CF2H)Ph to give Ph-CF2H (t1/2 = 144.7 min at 20 °C) with formation of the Pd(0)(PPh3)2/DPEphos catalyst.

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)

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.

Method for preparing alpha-aryl/heteroaryl/alkenyl-alpha,alpha-difluoromethyl compounds

The invention discloses a method for preparing alpha-aryl/heteroaryl/alkenyl-alpha,alpha-difluoromethyl compounds. The preparation method for the alpha-aryl/heteroaryl/alkenyl-alpha,alpha-difluoromethyl compounds as shown in a formula C which is described

Nickel-Catalyzed Difluoromethylation of Arylboronic Acids with Bromodifluoromethane

Although bromodifluoromethane (BrCF2H) is a simple and readily available fluorine source, direct formation of difluoromethylated arenes with BrCF2H has not been reported. Herein, we describe an efficient method to access difluoromethylated arenes through a nickel-catalyzed difluoromethylation of arylboronic acids with BrCF2H. The reaction exhibits high efficiency, good functional group tolerance and broad substrate scope, thus providing an efficient route for applications in drug discovery and development. Preliminary mechanistic studies reveal that a difluoromethyl radical is involved in the reaction.

Chlorodifluoromethane-triggered formation of difluoromethylated arenes catalysed by palladium

Difluoromethylated aromatic compounds are of increasing importance in pharmaceuticals, agrochemicals and materials. Chlorodifluoromethane (ClCF2H), an inexpensive, abundant and widely used industrial raw material, represents the ideal and most straightforward difluoromethylating reagent, but introduction of the difluoromethyl group (CF2H) from ClCF2H into aromatics has not been reported. Here, we describe a direct palladium-catalysed difluoromethylation method for coupling ClCF2H with arylboronic acids and esters to generate difluoromethylated arenes with high efficiency. The reaction exhibits a remarkably broad substrate scope, including heteroarylboronic acids, and was used for difluoromethylation of a range of pharmaceuticals and biologically active compounds. Preliminary mechanistic studies revealed that a palladium difluorocarbene intermediate is involved in the reaction. Although numerous metal-difluorocarbene complexes have been prepared, the catalytic synthesis of difluoromethylated or difluoromethylenated compounds involving metal-difluorocarbene complexes has not received much attention. This new reaction therefore also opens the door to understand metal- difluorocarbene complex catalysed reactions.

Access to Difluoromethylated Arenes by Pd-Catalyzed Reaction of Arylboronic Acids with Bromodifluoroacetate

An unprecedented example of Pd-catalyzed difluoromethylation of aryl boronic acids with bromodifluoroacetate is described. The reaction proceeds under mild reaction conditions with hydroquinone and Fe(acac)3 as additives. Preliminary mechanistic studies reveal that a difluorocarbene pathway is involved in the reaction, which is unusual compared to the most traditional approaches. This reaction has advantages of high efficiency and excellent functional group compatibility, even toward bromide and hydroxy group, thus providing a useful protocol for drug discovery and development.