Radical Conjugated Addition: Addition of Dialkyl Phosphonodifluoromethyl Radical onto Unsaturated Ketones

Addition reactions of perfluoroalkyl radicals to ordinary or polyfluorinated alkenes have been frequently used to synthesize perfluoroalkylated organic compounds. Here ethyl/methyl 2-bromo-2,2-difluoroacetate, diethyl (bromodifluoromethyl)phosphonate, [(bromodifluoromethyl)sulfonyl]benzene, and ethyl 2-bromo-2-fluoroacetate were involved in Na2S2O4-mediated radical additions to vinyl ethers in the presence of alcohols to give difluoro or monofluoroacetyl-substituted acetals or corresponding difluoromethylphosphonate- and (difluoromethylphenyl)sulfonyl-substituted alkyl acetals. This methodology has also been applied as a key step in the synthesis of hitherto unknown 3,3-difluoro-GABA, completing the series of isomeric difluoro GABAs. Comparison of the pKa values of 3-fluoro- and 3,3-difluoro-GABA with that of the fluorine free parent compound showed that introduction of each fluorine lead to acidification of both the amino and the carboxyl functions by approximately one unit.

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Synthesis of C₂-Symmetric gem-Difluoromethylenated Angular Triquinanes

Thaharn

Soorukram

Kuhakarn

et al. 2017

J. Org. Chem.

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A synthesis of symmetrical gem-difluoromethylenated angular triquinanes is described. The synthetic strategy involved sequential fluoride-catalyzed nucleophilic addition of PhSCFSiMe (1) to 2,2-diallylated or 2,2-dipropargylated indane-1,3-diones 2 followed by stereoselective radical cyclization of the resulting adducts 3 to provide the cyclized gem-difluoromethylenated diquinanes 4 as a mixture of stereoisomers. Repeated addition of 1 to 4 followed by cyclization resulted in the stereoselective synthesis of the desired C-symmetric gem-difluoromethylenated angular triquinanes 6 in good yields with high stereoselectivity.

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Radical Conjugated Addition: Addition of Dialkyl Phosphonodifluoromethyl Radical onto Unsaturated Ketones

Abstract: The free radical addition of phosphonodifluoromethyl radical is reported from iodophosphonate and sodium dithionite, triethylborane, or dilauroyl peroxide as initiator. Triethylborane promoted the radical conjugated addition onto enones.

Cited by 4 publications

References 9 publications

Halogenation of Alkenes and Dienes

Halogenation of Alkenes and Dienes

Radical Reactions of Alkyl 2-Bromo-2,2-difluoroacetates with Vinyl Ethers: “Omitted” Examples and Application for the Synthesis of 3,3-Difluoro-GABA

Synthesis of C₂-Symmetric gem-Difluoromethylenated Angular Triquinanes

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Radical Conjugated Addition: Addition of Dialkyl Phosphonodifluoromethyl Radical onto Unsaturated Ketones

Abstract: The free radical addition of phosphonodifluoromethyl radical is reported from iodophosphonate and sodium dithionite, triethylborane, or dilauroyl peroxide as initiator. Triethylborane promoted the radical conjugated addition onto enones.

Cited by 4 publications

References 9 publications

Halogenation of Alkenes and Dienes

Halogenation of Alkenes and Dienes

Radical Reactions of Alkyl 2-Bromo-2,2-difluoroacetates with Vinyl Ethers: “Omitted” Examples and Application for the Synthesis of 3,3-Difluoro-GABA

Synthesis of C2-Symmetric gem-Difluoromethylenated Angular Triquinanes

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Synthesis of C₂-Symmetric gem-Difluoromethylenated Angular Triquinanes