New Electrophilic Difluoromethylating Reagent

Prakash, G. K. Surya; Wéber, Csaba; Chacko, Sujith; Oláh, George A.

doi:10.1021/ol070195g

Cited by 133 publications

(61 citation statements)

References 18 publications

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“…In the case of triphenyl phosphine, only 15% conversion after 1 day of stirring at room temperature was observed. However, in the presence of at least 15% of diisopropylazodicarboxylate (DIAD), 100% conversion was achieved in 16 h. Other phosphines worked equally well under similar conditions (Scheme 32) [113].…”

Section: A-difluoromethyl Phosphinesmentioning

confidence: 93%

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New trends in the chemistry of α-fluorinated ethers, thioethers, amines and phosphines

Manteau

Pazenok

Vors

et al. 2010

Journal of Fluorine Chemistry

365

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Section: A-difluoromethyl Phosphinesmentioning

confidence: 93%

“…S-(Difluoromethyl)diarylsulfonium tetrafluoroborate was developed as a new electrophilic difluoromethylating agent (Scheme 31). However, this reagent cannot transfer the difluoromethyl group to phenols and secondary amines [113].…”

Section: A-difluoromethyl Aminesmentioning

confidence: 99%

New trends in the chemistry of α-fluorinated ethers, thioethers, amines and phosphines

Manteau

Pazenok

Vors

et al. 2010

Journal of Fluorine Chemistry

365

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“…For the synthesis of sulfur-containing heterocycles usually metal sulfides, thioesters, or thioethers are employed as starting materials, and first-or second-row transition-metal complexes serve as catalysts. To achieve C-C 9-12 or C-S [13][14][15][16][17][18][19][20] coupling involved in the ring closure process, activation of C-H, [9][10][11][12][13][14][15][16][17][18][19][20] C-X (X = Br or I) 15,18,20 or C-S 14,17 bonds is a prerequisite.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic aspects of the gas-phase coupling of thioanisole and chlorobenzene to dibenzothiophene catalyzed by atomic Ho⁺

Zhou

Schlangen

Schwarz

2015

Phys. Chem. Chem. Phys.

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Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Mechanistic aspects of the novel gas-phase generation of dibenzothiophene via coupling of thioanisole and chlorobenzene, employing atomic Ho+ as a catalyst, have been investigated using Fourier-transform ion cyclotron resonance mass spectrometry in conjunction with density functional theory (DFT) calculations.DFG, EXC 314, Unifying Concepts in Catalysi

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“…The difluoromethyl (CF 2 H) group is known to be isosteric and isopolar to a hydroxy (OH) and thiol (SH) unit. The CF 2 H group can also act as a more lipophilic hydrogen donor than OH and NH groups through hydrogen bonding [31][32][33][34]. Thus, the difluoromethylation of biologically active molecules is an effective strategy for the design new candidates of pharmaceuticals and agrochemicals [16].…”

Section: Introductionmentioning

confidence: 99%

Direct nucleophilic difluoromethylation of aromatic isoxazoles activated by electron-withdrawing groups using (difluoromethyl)trimethylsilane

Wang,

Tokunaga,

Shibata

2014

ScienceOpen Research

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The activation of aromatic diaryl isoxazoles with strong electron-withdrawing groups, such as the nitro, triflyl, and the phenylsulfonyl groups, at the 4-position has enabled the first regio-and diastereoselective difluoromethylation at the 5-position of isoxazoles by nucleophilic addition using (difluoromethyl) trimethylsilane, Me 3 SiCF 2 H, to provide difluoromethylated isoxazolines in good yields. Conjugated styryl-4-nitroisoxazoles were also nicely converted into the corresponding CF 2 H adducts with high regio-and excellent diastereoselectivities. Since the trifluoromethylated analogs of the corresponding diaryl-isoxazolines are effective ectoparasiticides, represented by fluralaner, should a series of difluoromethylated isoxazolines be obtained, they would be of great importance as promising drug candidates in this field.Heterocycles have an extensive history and are present in a wide variety of drugs, most vitamins, many natural products, biomolecules, and biologically active compounds [1][2][3][4]. Manmade fluorinated organic compounds have become a remarkable success in the pharmaceutical industry, despite their relatively young history [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. In this context, fluorinated heterocycles have gained attention as new drug candidates over the past few decades in medicine and agro-chemistry [21][22][23][24][25][26][27][28]. Fluorinated and trifluoromethylated compounds have been well targeted in this research area [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28], and difluoromethylated compounds are next [16,[21][22][23][24][25][26][27][28]. The difluoromethyl (CF 2 H) group is known to be isosteric and isopolar to a hydroxy (OH) and thiol (SH) unit. The CF 2 H group can also act as a more lipophilic hydrogen donor than OH and NH groups through hydrogen bonding [31][32][33][34]. Thus, the difluoromethylation of biologically active molecules is an effective strategy for the design new candidates of pharmaceuticals and agrochemicals [16]. BRAVECTO™ (fluralaner) is a highly potent insect and acarid RDL and GluCl inhibitor that was just recently approved in chewable tablets for dogs against fleas and ticks [35]. A systematically large number of research disclosed that 3,5-diaryl-5-(trifluoromethyl)-2-isoxazoline unit 1 is a key skeleton for its biological activity [36][37][38]. Since 2010, our group has also made contributions to this fascinating structure by the direct late-stage trifluoromethylation of aromatic isoxazoles with Ruppert-Prakash reagent (trifluoromethyl) trimethylsilane (Me 3 SiCF 3 ) [39][40]41], and a fluorinated building block strategy based on the use of inexpensive reagents under organocatalysis with an eye on industrial purposes [36][37][38]. We are now interested in the synthesis of difluoromethyl analogs of this key structure, i.e., 3,5-diaryl-5-(difluoromethyl)-2-isoxazolines 2. More than 27,000 isoxazolines 1 with a quaternary carbon bearing a CF 3 group at the 5-position have been s...

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New Electrophilic Difluoromethylating Reagent

Cited by 133 publications

References 18 publications

New trends in the chemistry of α-fluorinated ethers, thioethers, amines and phosphines

New trends in the chemistry of α-fluorinated ethers, thioethers, amines and phosphines

Mechanistic aspects of the gas-phase coupling of thioanisole and chlorobenzene to dibenzothiophene catalyzed by atomic Ho⁺

Direct nucleophilic difluoromethylation of aromatic isoxazoles activated by electron-withdrawing groups using (difluoromethyl)trimethylsilane

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New Electrophilic Difluoromethylating Reagent

Cited by 133 publications

References 18 publications

New trends in the chemistry of α-fluorinated ethers, thioethers, amines and phosphines

New trends in the chemistry of α-fluorinated ethers, thioethers, amines and phosphines

Mechanistic aspects of the gas-phase coupling of thioanisole and chlorobenzene to dibenzothiophene catalyzed by atomic Ho+

Direct nucleophilic difluoromethylation of aromatic isoxazoles activated by electron-withdrawing groups using (difluoromethyl)trimethylsilane

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Product

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Mechanistic aspects of the gas-phase coupling of thioanisole and chlorobenzene to dibenzothiophene catalyzed by atomic Ho⁺