- Ph2S/selectfluor-promoted deoxydifluorination of aldehydes
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The installation of a HCF2 group is a research area that has received increasing attention, and deoxydifluorination of aldehydes have served as an attractive protocol due to the wide availability of aldehydes. Herein we describe a Ph2/sub
- He, Guowen,Xiao, Xuan,Jin, Han-Zhou,Lin, Jin-Hong,Zhong, Tongsheng,Zheng, Xing,Xiao, Ji-Chang
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- Nickel-Catalyzed Difluoromethylation of Arylboronic Acids with Bromodifluoromethane
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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.
- Fu, Xia-Ping,Xiao, Yu-Lan,Zhang, Xingang
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supporting information
p. 143 - 146
(2018/01/05)
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- Method for preparing alpha-aryl/heteroaryl/alkenyl-alpha,alpha-difluoromethyl compounds
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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
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Paragraph 0141; 0142; 0143; 0150; 0151; 0152; 0159; 0160
(2018/09/08)
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- Containing fluoromethyl compound and its preparation method
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The invention discloses a compound containing difluromethylation and a preparation method therefor. The invention provides a preparation method of a compound RCF2H containing the difluromethylation. The preparation method comprises the following steps of: under the protection of inert gas, performing a coupling reaction on a compound RX and trimethyl difluromethylation silicon in an organic solvent under the existing conditions of a palladium catalyst, a ligand and alkali so as to obtain the compound RCF2H containing the difluromethylation. Through the adoption of the difluromethylation reaction of the compound disclosed by the invention, the difluromethylation of the compound with various aryl halogen compounds such as aryl iodide, aryl bromide and natural products (such as estrone or vitamin E) can be realized, the conditions of the type of reactions are mild, raw materials are cheap and easy to obtain, the conversion rate of the reaction is high, the compatibility of base groups is good, and the compound has a good market application prospect. RX+TMSCF2H -> RCF2H
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Paragraph 0073; 0121-0124
(2017/10/05)
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- Chlorodifluoromethane-triggered formation of difluoromethylated arenes catalysed by palladium
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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.
- Feng, Zhang,Min, Qiao-Qiao,Fu, Xia-Ping,An, Lun,Zhang, Xingang
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p. 918 - 923
(2017/09/01)
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- CF2H, a Hydrogen Bond Donor
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The CF2H group, a potential surrogate for the OH group, can act as an unusual hydrogen bond donor, as confirmed by crystallographic, spectroscopic, and computational methods. Here, we demonstrate the bioisosterism of the OH and CF2H
- Sessler, Chanan D.,Rahm, Martin,Becker, Sabine,Goldberg, Jacob M.,Wang, Fang,Lippard, Stephen J.
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supporting information
p. 9325 - 9332
(2017/07/22)
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- Pd-Catalyzed Transfer of Difluorocarbene
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The study of transition-metal difluorocarbene complex has long been a subject of active investigation, but the transition-metal-catalyzed transfer of difluorocarbene remains a significant challenge. The Pd-catalyzed transfer of difluorocarbene is described to realize the coupling reaction of boronic acids with difluorocarbene to give (difluoromethyl)arenes and -olefins. Mechanistic investigations reveal that the Pd? -CF2 complex is an important intermediate for this transformation. This complex is prone to trimerization without the presence of starting materials.
- Deng, Xiao-Yun,Lin, Jin-Hong,Xiao, Ji-Chang
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supporting information
p. 4384 - 4387
(2016/11/01)
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- Access to Difluoromethylated Arenes by Pd-Catalyzed Reaction of Arylboronic Acids with Bromodifluoroacetate
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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.
- Feng, Zhang,Min, Qiao-Qiao,Zhang, Xingang
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supporting information
p. 44 - 47
(2016/01/15)
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- DIFLUOROMETHYL ZINC COMPOUND
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PROBLEM TO BE SOLVED: To provide a production method of difluoromethyl group-containing aromatic compounds which are useful as synthetic intermediates. SOLUTION: A difluoromethyl zinc-TALED complex compound is derived from a bis(trifluoromethyl)zinc-DMPU complex compound (DMPU represents N,N'-dimethylpropylene urea) and represented by formula (1). A production method of a difluoromethyl group-containing aromatic compound has a step to conduct a difluoromethylation reaction by using the difluoromethyl zinc-TALED complex compound. CHF2-Zn.TALED(1)(TALED is a tetraalkylethylenediamine). SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0047-0049
(2017/04/03)
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- Minimal Self-Immolative Probe for Multimodal Fluoride Detection
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Two single-molecule, self-immolative fluoride probes, namely tert-butyldimethylsilyl-protected 2- and 4-difluoromethylphenol, are described. Compared to similar systems previously described, the probes are characterized by a simpler structure and straightforward, two-step preparation. Nevertheless, they allow the detection of fluoride ions at micromolar concentration by the naked eye, UV-vis absorption, and fluorescence. A detailed investigation of the self-immolative reaction reveals that the rate-limiting step is the release of the first fluoride ion from the difluoromethylphenolate intermediate. Moreover, the mutual position of the difluoromethyl- and tert-butyldimethylsilyl-protected residues has a relevant effect on the reactivity. Likely, a CF2H-O hydrogen bond in the 2-isomer increases the reactivity of the silyl ether toward hydrolytic cleavage but also stabilizes the phenolate intermediate, slowing the release of fluoride ions.
- Gabrielli, Luca,Mancin, Fabrizio
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p. 10715 - 10720
(2016/11/29)
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- DIFLUOROMETHYLATION OF ARYL AND VINYL IODIDES
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Selectively fluorinated molecules are important as materials, pharmaceuticals, and agrochemicals, but their synthesis by simple, mild, laboratory methods is challenging. We report a straightforward method for the cross-coupling of a difluoromethyl group w
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Paragraph 0075; 0077
(2013/09/26)
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- Copper-mediated difluoromethylation of aryl and vinyl iodides
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Selectively fluorinated molecules are important as materials, pharmaceuticals, and agrochemicals, but their synthesis by simple, mild, laboratory methods is challenging. We report a straightforward method for the cross-coupling of aryl and vinyl iodides with a difluoromethyl group generated from readily available reagents to form difluoromethylarenes and difluoromethyl-substituted alkenes. The reaction of electron-neutral, electron-rich, and sterically hindered aryl and vinyl iodides with the combination of CuI, CsF and TMSCF2H leads to the formation of difluoromethyl-substituted products in high yield with good functional group compatibility. This transformation is surprising, in part, because of the prior observation of the instability of CuCF2H.
- Fier, Patrick S.,Hartwig, John F.
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supporting information; experimental part
p. 5524 - 5527
(2012/05/20)
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- Synthesis and evaluation of general mechanism-based inhibitors of sulfatases based on (difluoro)methyl phenyl sulfate and cyclic phenyl sulfamate motifs
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Several model mechanism-based inhibitors (MbIs) were designed and evaluated for their ability to inhibit sulfatases. The MbI motifs were based on simple aromatic sulfates, which are known to be commonly accepted substrates across this highly conserved enzyme class, so that they might be generally useful for sulfatase labeling studies. (Difluoro)methyl phenol sulfate analogs, constructed to release a reactive quinone methide trap, were not capable of irreversibly inactivating the sulfatase active site. On the other hand, the cyclic sulfamates (CySAs) demonstrated inhibition profiles consistent with an active site-directed mode of action. These molecules represent a novel scaffold for labeling sulfatases and for probing their catalytic mechanism.
- Hanson, Sarah R.,Whalen, Lisa J.,Wong, Chi-Huey
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p. 8386 - 8395
(2008/02/05)
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