- Efficient asymmetric synthesis of aryl difluoromethyl sulfoxides and their use to access enantiopure α-difluoromethyl alcohols
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The -CHF2 moiety has shown a growing interest in pharmaceutical and agrochemical applications over the last few years. Its introduction is therefore a current research topic for organic chemists. Several groups have reported the synthesis of di
- Batisse, Chloé,Céspedes Dávila, Maria F.,Castello, Marco,Messara, Amélia,Vivet, Bertrand,Marciniak, Gilbert,Panossian, Armen,Hanquet, Gilles,Leroux, Frédéric R.
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p. 3063 - 3079
(2019/05/07)
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- Visible light-promoted difluoromethylthiolation of aryldiazonium salts
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Difluoromethylthiolation of aryldiazonium salts under photocatalytic conditions with a shelf-stable, easily prepared and inexpensive reagent, PhSO2SCF2H was described. A variety of difluoromethylthioethers were obtained utilizing aryldiazonium salts containing different functional groups. Aryldiazonium salts with a heteroarene moiety were tolerated. Fluorescence quenching experiments indicated that both oxidative and reductive quenching cycles occurred during this process.
- Wang, Wengui,Zhang, Shuxiang,Zhao, Huaiqing,Wang, Shoufeng
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p. 8565 - 8568
(2018/11/27)
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- Radical Difluororomethylation of Thiols with Difluoromethylphosphonium Triflate under Photoredox Catalysis
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A convenient, visible light-induced radical difluoromethylation of aryl-, heteroaryl-, and alkylthiols with difluoromethyltriphenylphosphonium triflate was developed to afford various difluoromethyl thioethers in moderate to excellent yields. The key reaction features include the use of a readily available CF2H radical source, mild reaction conditions, and excellent chemoselective thiol-difluoromethylation.
- Ran, Yang,Lin, Qing-Yu,Xu, Xiu-Hua,Qing, Feng-Ling
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p. 7373 - 7378
(2017/07/26)
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- Difluoro methylation reagent, preparation method and application thereof (by machine translation)
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The present invention discloses a two-trifluoromethylation of the reagent, preparation method and application thereof. The invention [...] methylation reagent preparation process is simple, high yield; and the reagent can be a more moderate, high-efficiently the sulfonic acid, alcohol, carbonyl and on the α carbon atom of the difluoromethyl. (by machine translation)
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Paragraph 0128; 0129; 0130; 0140; 0141; 0142
(2017/10/23)
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- Difluoromethyl bioisostere: Examining the lipophilic hydrogen bond donor concept
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There is a growing interest in organic compounds containing the difluoromethyl group, as it is considered a lipophilic hydrogen bond donor that may act as a bioisostere of hydroxyl, thiol, or amine groups. A series of difluoromethyl anisoles and thioanisoles was prepared and their druglike properties, hydrogen bonding, and lipophilicity were studied. The hydrogen bond acidity parameters A (0.085-0.126) were determined using Abraham's solute 1H NMR analysis. It was found that the difluoromethyl group acts as a hydrogen bond donor on a scale similar to that of thiophenol, aniline, and amine groups but not as that of hydroxyl. Although difluoromethyl is considered a lipophilicity enhancing group, the range of the experimental Δlog P(water-octanol) values (log P(XCF2H) - log P(XCH3)) spanned from -0.1 to +0.4. For both parameters, a linear correlation was found between the measured values and Hammett σ constants. These results may aid in the rational design of drugs containing the difluoromethyl moiety.
- Zafrani, Yossi,Yeffet, Dina,Sod-Moriah, Gali,Berliner, Anat,Amir, Dafna,Marciano, Daniele,Gershonov, Eytan,Saphier, Sigal
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p. 797 - 804
(2017/02/05)
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- Visible-Light Photoredox Difluoromethylation of Phenols and Thiophenols with Commercially Available Difluorobromoacetic Acid
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A simple and efficient visible-light photoredox one-pot method for difluoromethylation of phenols and thiophenols has been developed. The protocol uses commercially available, inexpensive, and easy handling difluorobromoacetic acid as the difluoromethylating agent, and the diverse O- and S-difluoromethylated products were prepared in good yields with tolerance of many functional groups.
- Yang, Jinyan,Jiang, Min,Jin, Yunhe,Yang, Haijun,Fu, Hua
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supporting information
p. 2758 - 2761
(2017/05/24)
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- Preparation of difluoromethylthioethers through difluoromethylation of disulfides using TMS-CF2H
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We report an operationally simple, metal-free approach for the late-stage introduction of the important lipophilic hydrogen-bond donor motif, SCF2H. This reaction converts diaryl- and dialkyl-disulfides into the corresponding aryl/alkyl-SCF2H through the nucleophilic transfer of a difluoromethyl group with good functional group tolerance. This method is notable for its use of commercially available TMSCF2H, and does not rely on the need for handling of sensitive metal complexes.
- Howard, Joseph L.,Schotten, Christiane,Alston, Stephen T.,Browne, Duncan L.
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supporting information
p. 8448 - 8451
(2016/07/07)
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- PhSO2SCF2H: A Shelf-Stable, Easily Scalable Reagent for Radical Difluoromethylthiolation
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A new shelf-stable and easily scalable difluoromethylthiolating reagent S-(difluoromethyl) benzenesulfonothioate (PhSO2SCF2H) was developed. PhSO2SCF2H is a powerful reagent for radical difluoromethylthiolation of aryl and alkyl boronic acids, decarboxylative difluoromethylthiolation of aliphatic acids, and a phenylsulfonyl-difluoromethylthio difunctionalization of alkenes under mild reaction conditions.
- Zhu, Dianhu,Shao, Xinxin,Hong, Xin,Lu, Long,Shen, Qilong
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supporting information
p. 15807 - 15811
(2016/12/16)
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- 18F-Labeling of Aryl-SCF3, -OCF3 and -OCHF2 with [18F]Fluoride
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We report that halogenophilic silver(I) triflate permits halogen exchange (halex) nucleophilic 18F-fluorination of aryl-OCHFCl, -OCF2Br and -SCF2Br precursors under mild conditions. This AgI-mediated process allows for the first time access to a range of 18F-labeled aryl-OCHF2, -OCF3 and -SCF3 derivatives, inclusive of [18F]riluzole. The 18F-labeling of these medicinally important motifs expands the radiochemical space available for PET applications. A halogen exchange (halex) 18F-fluorination process offers access for the first time to 18F-labeled arylOCF3, arylOCHF2 and arylSCF3, three motifs of established medicinal importance in PET radiotracers. The use of silver(I) triflate is critical to permit 18F-labeling under mild conditions.
- Khotavivattana, Tanatorn,Verhoog, Stefan,Tredwell, Matthew,Pfeifer, Lukas,Calderwood, Samuel,Wheelhouse, Katherine,Leecollier, Thomas,Gouverneur, Vronique
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supporting information
p. 9991 - 9995
(2015/08/19)
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- Direct S-difluoromethylation of thiols using the Ruppert-Prakash reagent Dedicated to Prof. Veronique Gouverneur on the occasion of receiving the ACS Award for Creative Work in Fluorine Chemistry.
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Direct S-difluoromethylation of aryl and aliphatic thiols using the Ruppert-Prakash reagent is demonstrated. The reaction produces trimethylsilyldifluoromethyl sulfides, which upon cleavage with fluoride produces the difluoromethyl sulfides. The key reaction features are the use of relatively inexpensive and commercially available starting materials, shorter reaction times, ambient temperatures, easy reaction procedure, and selective S-difluoromethylation in the presence of -OH, -NH2 and -CO2H functional groups. Furthermore, one-pot arylthiodifluoromethyl transfer to PhCHO is also demonstrated.
- Prakash, G.K. Surya,Krishnamoorthy, Sankarganesh,Kar, Sayan,Olah, George A.
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p. 186 - 191
(2015/10/28)
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- Copper-promoted sandmeyer difluoromethylthiolation of aryl and heteroaryl diazonium salts
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An efficient copper-promoted difluoromethylthiolation of aryl and heteroaryl diazonium salts is described. The reaction is conducted under mild reaction conditions and various functional groups were compatible. In addition, reactions of heteroaryl diazonium salts such as pyridyl, quinolinyl, benzothiazolyl, thiophenyl, carbazolyl, and pyrazolyl diazonium salts occurred smoothly to afford the medicinally important difluoromethylthiolated heteroarenes. Furthermore, a more practical one-pot direct diazotization and difluoromethylthiolation protocol was developed, and it converts the aniline derivatives into difluoromethylthiolated arenes. The utility of the method is demonstrated by difluoromethylthiolation of a number of natural products and drug molecules. A dose of salt: The title reaction is conducted under mild reaction conditions and various functional groups are compatible. (Hetero)aryl diazonium salts reacted smoothly to afford the medicinally important difluoromethylthiolated (hetero)arenes. A practical one-pot direct diazotization and difluoromethylthiolation protocol was developed for aniline derivatives to generate difluoromethylthiolated arenes.
- Wu, Jiang,Gu, Yang,Leng, Xuebing,Shen, Qilong
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supporting information
p. 7648 - 7652
(2015/06/25)
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- S-, N-, and Se-difluoromethylation using sodium chlorodifluoroacetate
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A simple protocol for the difluoromethylation of thiols is reported using chlorodifluoroacetate as the difluoromethylating agent. This cheap reagent undergoes smooth decarboxylation at 95 C to afford difluorocarbene, which can be trapped with a variety of aromatic and heteroaromatic thiols. The reaction is also effective for the difluoromethylation of heterocyclic nitrogen compounds and phenylselenol.
- Mehta, Vaibhav P.,Greaney, Michael F.
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supporting information
p. 5036 - 5039
(2013/10/22)
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- Diethyl bromodifluoromethylphosphonate: a highly efficient and environmentally benign difluorocarbene precursor
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A convenient method for the difluoromethylation of phenols and thiophenols, using diethyl bromodifluoromethylphosphonate (1) as a difluorocarbene precursor, is described. This commercially available phosphonate was found to undergo an extremely facile P-C
- Zafrani, Yossi,Sod-Moriah, Gali,Segall, Yoffi
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experimental part
p. 5278 - 5283
(2009/11/30)
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- The reactions of difluorodiiodomethane with nucleophiles
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Treatment of difluorodiiodomethane with phenoxides (ArO-) in DMF at room temperature gives ArOCF2I in 7-15%, the carbonates (ArOCO2Ar) being the major products, while with thiophenoxides affords difluoromethylene derivativ
- Guo, Yong,Chen, Qing-Yun
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p. 105 - 109
(2007/10/03)
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- IMPROVEMENT OF THE SYNTHESIS OF ARYL DIFLUOROMETHYL ETHERS AND THIOEHTERS BY USING A SOLID-LIQUID PHASE-TRANSFER TECHNIQUE
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A new solid-liquid phase-transfer technique has been used to synthesize aryl difluoromethyl ehters and thioethers.Phenols (or thiophenols) and chlorodifuoromethane, dissolved in a cheap aprotic solvent of low polarity, are contacted with solid sodium hydroxide in the presence of a catalytic amount of tris-(3,6-dioxaheptyl)amine.The work-up of the reaction mixtures is very simple.Although yields are similar in both homogeneous and heterogeneous procedures using phenols, improved yields are obtained for thiophenols when using phase-transfer conditions.
- Langlois, Bernard R.
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p. 247 - 262
(2007/10/02)
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