24933-63-9Relevant academic research and scientific papers
Radical Difluoromethylation of Thiols with (Difluoromethyl)triphenylphosphonium Bromide
Heine, Niklas B.,Studer, Armido
, p. 4150 - 4153 (2017)
A method for facile difluoromethylation of various thiols using (difluoromethyl)triphenylphosphonium bromide under mild reaction conditions is presented. The transformation proceeds in the absence of any transition metal using a bench-stable and readily accessible phosphonium salt. Deuterium labeling experiments and cyclic voltammetry measurements reveal that the difluoromethylation occurs via a SRN1-type mechanism. Substrate scope is broad, and various functional groups are tolerated (OH, NH2, amide, ester).
Difluoromethylation of Phenols and Thiophenols with the S-(Difluo-romethyl)sulfonium Salt: Reaction, Scope, and Mechanistic Study
Liu, Guo-Kai,Qin, Wen-Bing,Li, Xin,Lin, Li-Ting,Wong, Henry N. C.
, p. 15948 - 15957 (2019/11/16)
A facile and practical approach for the difluoromethylation of phenols and thiophenols was described. Making use of the recently developed bench-stable S-(difluoromethyl)sulfonium salt as the difluorocarbene precursor, a wide variety of diversely functionalized phenols and thiophenols were readily converted to their corresponding aryl difluoromethyl ethers in good to excellent yields in the presence of lithium hydroxide. Chemoselectivity of various O,S-nucleophiles toward difluorocarbene was systematically studied, suggesting the reactivity order ArS- > RS-, ArO- > ROH > RO-, ArSH, ArOH, RSH.
Difluoromethyl bioisostere: Examining the lipophilic hydrogen bond donor concept
Zafrani, Yossi,Yeffet, Dina,Sod-Moriah, Gali,Berliner, Anat,Amir, Dafna,Marciano, Daniele,Gershonov, Eytan,Saphier, Sigal
, p. 797 - 804 (2017/02/05)
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.
Radical Difluororomethylation of Thiols with Difluoromethylphosphonium Triflate under Photoredox Catalysis
Ran, Yang,Lin, Qing-Yu,Xu, Xiu-Hua,Qing, Feng-Ling
, p. 7373 - 7378 (2017/07/26)
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.
PhSO2SCF2H: A Shelf-Stable, Easily Scalable Reagent for Radical Difluoromethylthiolation
Zhu, Dianhu,Shao, Xinxin,Hong, Xin,Lu, Long,Shen, Qilong
supporting information, p. 15807 - 15811 (2016/12/16)
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.
A Route to α-Fluoroalkyl Sulfides from α-Fluorodiaroylmethanes
Lin, Ya-Mei,Yi, Wen-Bin,Shen, Wan-Zhao,Lu, Guo-Ping
supporting information, p. 592 - 595 (2016/02/18)
α,α-Difluorodiaroylmethane can be used as a nucleophilic difluoromethylation reagent for generating α-thioaryl-α,α-difluoroacetophenones (Ar1COCF2SAr) and difluoromethylthiolated arenes (ArSCF2H) under transition-metal-free conditions. The reaction selectivity is mainly dependent on temperature. The method has also been extended to the synthesis of α-thioaryl-α-monofluoroacetophenones using α-monofluorodibenzoylmethane. Moreover, the benzoyl cation derived from α,α-difluorodibenzoylmethane can react with nucleophiles to afford the desired products in a one-pot process.
Difluoromethylthiolation reagent, and preparation method and application thereof
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Paragraph 0128; 0129; 0130; 0131, (2017/07/22)
The invention discloses a difluoromethylthiolation reagent 1, and a preparation method and application thereof. The invention provides application of the difluoromethylthiolation reagent 1 to preparation of a compound containing a difluoromethylthio group. A method 1 or method 2 is adopted for the application. The method 1 comprises a step of subjecting a compound as shown in a formula 2 which is described in the specification and the difluoromethylthiolation reagent 1 to a nucleophilic substitution reaction in an organic solvent in the presence of protective gas, alkali, copper salt and ligand, wherein the alkali is one or more selected from a group consisting of sodium carbonate, lithium carbonate, potassium fluoride, potassium phosphorate and lithium hydroxide monohydrate. The method 1 comprises a step of subjecting a compound as shown in a formula 3 which is described in the specification and the difluoromethylthiolation reagent 1 to a nucleophilic substitution reaction in an organic solvent in the presence of protective gas. The methods provided by the invention can introduce a difluoromethylthio group through a one-step reaction and have the advantages of a wide scope of applicable substrates, mild reaction conditions, a high reaction conversion rate, high yield, high product purity and good industrial production prospects.
N-Difluoromethylthiophthalimide: A Shelf-Stable, Electrophilic Reagent for Difluoromethylthiolation
Zhu, Dianhu,Gu, Yang,Lu, Long,Shen, Qilong
supporting information, p. 10547 - 10553 (2015/09/28)
A new, electrophilic difluoromethylthiolating reagent N-difluoromethylthiophthalimide 3 was developed. Reagent 3 can be readily synthesized in four steps from easily available starting materials phthalimide and TMSCF2H. N-difluoromethylthiophthalimide 3 is a powerful electrophilic difluoromethylthiolating reagent that allows the difluoromethylthiolation of a wide range of nucleophiles including aryl/vinyl boronic acids, alkynes, amines, thiols, β-ketoesters, and oxindoles and electron-rich heteroarenes such as indole, pyrrole, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,2-a]pyridine, aminothiazole, isoxazole, and pyrazole under mild conditions.
Copper-promoted sandmeyer difluoromethylthiolation of aryl and heteroaryl diazonium salts
Wu, Jiang,Gu, Yang,Leng, Xuebing,Shen, Qilong
supporting information, p. 7648 - 7652 (2015/06/25)
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.
Synthesis of difluoromethyl thioethers from difluoromethyl trimethylsilane and organothiocyanates generated in situ
Bayarmagnai, Bilguun,Matheis, Christian,Jouvin, Kvin,Goossen, Lukas J.
, p. 5753 - 5756 (2015/06/10)
A copper-CF2H complex generated in situ from copper thiocyanate and TMS-CF2H smoothly converts organothiocyanates into valuable difluoromethyl thioethers. This reaction step can be combined with several thiocyanation methods to one-pot protocols, allowing late-stage difluoromethylthiolations of widely available alkyl halides and arenediazonium salts. This strategy enables the introduction of difluoromethylthio groups - a largely unexplored substituent with highly promising properties - into drug-like molecules. A copper-CF2H complex generated in situ from copper thiocyanate and TMS-CF2H smoothly converts organothiocyanates into valuable difluoromethyl thioethers. This reaction step can be combined with several thiocyanation methods to one-pot protocols, allowing late-stage difluoromethylthiolations of widely available alkyl halides and arenediazonium salts.
