Synthesis of 2,2-Difluoro-3-hydroxy-1,4-diketones via an HFIP-Catalyzed Mukaiyama Aldol Reaction of Glyoxal Monohydrates with Difluoroenoxysilanes

Yang, Jianguo; Liu, Saimei; Peng, Hong; Li, Jin‐Shan; Wang, Zhiming; Ren, Jing

doi:10.1021/acs.joc.1c02504

Cited by 19 publications

(7 citation statements)

References 46 publications

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“…To our delight, the reaction under neat conditions using 2.0 equiv. of 2a at room temperature (Table 1, entry 1) led to the direct formation of gem-difluorinated 2-hydroxy-1,4-dicarbonyl adduct 3a in 91% yield, smoothly, after only 4 h. The reaction time was greatly reduced in comparison with our previous experiment results, using HFIP as the catalyst and DCM as solvent [26]. Then, a reduced amount of difluoroenoxysilane 2a (1.0 equiv, entry 2) was investigated to obtain a higher reaction utilization.…”

Section: Resultsmentioning

confidence: 57%

Solvent- and Catalyst-Free Synthesis of gem-Difluorinated and Polyfluoroarylated Compounds with Nucleophilic or Electrophilic Fluorine-Containing Reaction Partners, Respectively

Li,

2024

Molecules

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A novel, efficient and environmentally friendly solvent-free and catalyst-free approach for the synthesis of structurally diverse gem-difluorinated and polyfluoroarylated derivatives with readily available nucleophilic and electrophilic fluorine-containing reaction partners, difluoroenoxysilane and pentafluorobenzaldehyde, is described. This neat protocol is induced by the direct hydrogen-bond interactions between fluorinated and non-fluorinated reactants without the use of heavy metal catalysts or volatile organic solvents and with no need for column chromatographic separation for most cases.

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Section: Resultsmentioning

confidence: 57%

Solvent- and Catalyst-Free Synthesis of gem-Difluorinated and Polyfluoroarylated Compounds with Nucleophilic or Electrophilic Fluorine-Containing Reaction Partners, Respectively

Li,

2024

Molecules

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“…图式 5 二氟烯醇硅醚参与的高效"水上"无催化亲核加成反应 Scheme 5 Highly efficient "on water" catalyst-free nucleophilic addition reactions using fluorinated silyl enol ethers [20] 苯酞结构单元存在于许多天然产物、生物活性化合物和药物分子中 [21] . 2022 年, 任君课题组 [22] 报道了一例以对甲苯磺酸…”

Section: -10unclassified

Difluorinated Silyl Enol Ethers as Fluorine-Containing Building Blocks for the Synthesis of Organofluorine Compounds

Guo¹,

Yu²,

Chen³

et al. 2022

Chinese Journal of Organic Chemistry

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Organofluorine compounds have been widely applied in various fields ranging from drug discovery, clinical medicines, agrochemistry, and materials science to organic synthesis, due to their special chemical and physical properties when compared with nonfluorinated analogs. In the past decades, significant progress has been made in the development of selective fluorination and fluoroalkylation for the synthesis of structurally diverse fluorine-containing molecules. Among them, the α-fluoroalkylated carbonyl group represents an important class of scaffold components in biologically active and druglike compounds. In this context, based on the use of difluorinated silyl enol ether (DFSEE) as a unique fluoroaklylating reagent, a variety of methods for the incorporation of gem-difluoroalkylated carbonyl moiety have been achieved, including aldol, Mannich, arylation, allylation, protonation, halogenation, conjugate addition, and olefination reactions. On the other hand, DFSEEs could also merge with new types of reactions such as radical-type difluoroalkylation and cascade reaction by virtue of their incredible reactive flexibility. In addition, the O-site selective addition of DFSEEs was also reported, enabling the construction of versatile gem-difluoroalkenes. Given the importance of organofluorine compounds and the synthetic potential of these avenues, herein, we highlight the recent advances in the functionalization of gem-difluorinated silyl enol ethers, which serve as key fluorine-containing building blocks for the synthesis of organofluorine compounds.

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“…On the basis of related references and our studies, a plausible mechanism for HFIP-promoted selective hydroxyalkylation of aniline derivatives with arylglyoxal hydrates was proposed as shown in Scheme . First, the arylglyoxal hydrates 1 have a tendency to remove the water to form dehydrated ketoaldehydes 1′ in the presence of HFIP.…”

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confidence: 91%

HFIP-Promoted Selective Hydroxyalkylation of Aniline Derivatives with Arylglyoxal Hydrates

et al. 2022

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A HFIP-promoted highly selective hydroxyalkylation of aniline derivatives with arylglyoxal hydrates has been realized. The reaction produces various N,N-dialkylanilines and their derivatives with α-hydroxy carbonyl units in good to excellent yields under mild conditions. Furthermore, the synthetic potential of this method has been demonstrated by the facile synthesis of several structurally interesting molecules such as benzil, 1,2,4-triazine, quinoxaline, hydantoin, and 2-thiohydantoin with aromatic amine units.

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Synthesis of 2,2-Difluoro-3-hydroxy-1,4-diketones via an HFIP-Catalyzed Mukaiyama Aldol Reaction of Glyoxal Monohydrates with Difluoroenoxysilanes

Cited by 19 publications

References 46 publications

Solvent- and Catalyst-Free Synthesis of gem-Difluorinated and Polyfluoroarylated Compounds with Nucleophilic or Electrophilic Fluorine-Containing Reaction Partners, Respectively

Solvent- and Catalyst-Free Synthesis of gem-Difluorinated and Polyfluoroarylated Compounds with Nucleophilic or Electrophilic Fluorine-Containing Reaction Partners, Respectively

Difluorinated Silyl Enol Ethers as Fluorine-Containing Building Blocks for the Synthesis of Organofluorine Compounds

HFIP-Promoted Selective Hydroxyalkylation of Aniline Derivatives with Arylglyoxal Hydrates

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