Phenyl trifluorovinyl sulfide: a radical acceptor for preparation of gem-difluoromethylene compounds

Okano, Takashi; Chokai, Masayuki; Hiraishi, Makiko; Yoshizawa, Michito; Kusukawa, Takahiro; Fujita, Makoto

doi:10.1016/j.tet.2004.03.020

Cited by 17 publications

(16 citation statements)

References 24 publications

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“…However, these accounts also reveal that despite considerable effort, this species has remained elusive. Early on, Feiring 52 had attempted to synthesize this compound, but observed that unwanted hydrofluorination of the fluorovinyl compound yielded β,β,β-trifluoroethyl phenyl sulfone. In later studies, Percy was able to synthesize chlorodifluoroethyl phenyl sulfone from chlorodifluoroethanol 53 using a modified protocol previously reported by Kotsuki.…”

Section: Resultsmentioning

confidence: 99%

“…β,β-Difluorovinyl phenyl sulfone was pursued as an attractive candidate (Figure ). To be sure, there is keen interest in electrophilic, fluorinated α,β-unsaturated sulfones, particularly as dienophiles for [4π+2 π] cycloadditions and as reactive electrophiles in conjugate addition reactions. , Indeed, a careful examination of the literature uncovers previous attempts to synthesize β,β-difluorovinyl phenyl sulfone as a potential Diels–Alder dienophile. However, these accounts also reveal that, despite considerable effort, this species has remained elusive.…”

Section: Results and Discussionmentioning

confidence: 99%

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Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators

et al. 2017

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Developing specific chemical functionalities to deploy in biological environments for targeted enzyme inactivation lies at the heart of mechanism-based inhibitor (MBI) development, but also is central to other protein-tagging methods in modern chemical biology including activity-based protein profiling (ABPP) and proteolysis-targeting chimeras (PROTACS). We describe here a previously unknown class of potential PLP enzyme inactivators; namely, a family of quaternary, α-(1′fluoro)vinyl amino acids, bearing the side chains of the cognate amino acids. These are obtained by the capture of suitably protected amino acid enolates with β,β-difluorovinyl phenyl sulfone, a new 1′-fluorovinyl cation equivalent, and an electrophile that previously eluded synthesis, capture and characterization. A significant variety of biologically relevant AA-side chains are tolerated including those for alanine, valine, leucine, methionine, lysine, phenylalanine, tyrosine and tryptophan. Following addition/elimination, the resulting transoid α-(1′-fluoro)-β-(phenylsulfonyl)vinyl AA esters undergo smooth sulfone-stannane interchange to stereoselectively give the corresponding transoid α-(1′fluoro)-β-(tributylstannyl)vinyl AA esters. Protodestannylation and global deprotection then yields these sterically encumbered and densely functionalized, quaternary amino acids. The α-(1′fluoro)vinyl trigger, a potential allene-generating functionality originally proposed by Abeles, is now available in a quaternary AA context for the first time. In an initial test of this new inhibitor class, α-(1′-fluoro)vinyllysine is seen to act as a time dependent, irreversible inactivator of lysine decarboxylase from Hafnia alvei. The enantiomers of the inhibitor could be resolved and each is seen to give time dependent inactivation with this enzyme. Kitz-Wilson analysis reveals similar inactivation parameters for the two antipodes, L-α-(1′-fluoro)vinyllysine (Ki = 630 ± 20 μM; t1/2 = 2.8 min) and D-α-(1′-fluoro)vinyllysine (Ki = 470 ± 30 μM; t1/2 = 3.6 min). The stage is now set for exploration of the efficacy of this trigger in other PLP-enzyme active sites.

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Section: Resultsmentioning

confidence: 99%

Section: Results and Discussionmentioning

confidence: 99%

Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators

et al. 2017

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“…Nonactivated olefins, entries 10 and 11, gave low yields of the products 4f and 4g . These results suggest the nucleophilic character of the radical 2 9b…”

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confidence: 86%

“…Limited examples have been reported on the introduction of the gem -difluoromethylene moiety . Radical, carbene, and ionic reactions involving gem -difluorinated carbon species have been utilized. New and convenient methods for the synthesis of gem -difluoromethylene compounds, involving readily available sources of gem -difluorinated compounds, are still highly desirable.…”

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confidence: 99%

Difluorophenylsulfanylmethyl Radical and Difluoromethylene Diradical Synthons: gem-Difluoromethylene Building Block

et al. 2004

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Bromodifluorophenylsulfanylmethane has been demonstrated to be a highly versatile gem-difluoromethylene (CF2) building block via the reaction of difluorophenylsulfanylmethyl radical with olefins. gem-Difluoroalkenes and products containing a midchain CF2 group and with manipulatable functionality can be readily synthesized. The first example of a gem-difluoromethylene radical synthon is also reported.

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“…The proton of the tetraflate group appears to be stable in the presence of strong bases. , 4- tert -Butylphenyl tetraflate was treated with n -BuLi in Et 2 O for 30 min at −78 °C followed by methanol- d 4 quench. Starting tetraflate was recovered in 40% yield.…”

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Preparation and Synthetic Applications of Aryl Tetraflates (ArOSO₂CF₂CF₂H)

et al. 2007

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We have recently developed an improved synthetic route to 1,1,2,2-tetrafluoroethanesulfonic acid (HCF2CF2SO3H, TFESA) and explored the applications of this newly available superacid in catalysis. Low volatility, ease of handling, and a convenient 1H NMR handle make this acid an attractive alternative to triflic acid. TFESA can also be converted to several of its derivatives: anhydride, sulfonyl chloride, and sulfonyl fluoride, which provide a good entry point for the synthesis of aryl sulfonates. We prepared several aryl esters of 1,1,2,2-tetrafluoroethanesulfonic acid (aryl tetraflates) and showed that they can be used in a number of palladium-catalyzed coupling reactions (Suzuki, Heck, and Buchwald-Hartwig couplings). While the reactivity of tetraflates lies between that of triflates and chlorides, tetraflates appear to be more thermally stable. Additionally, the presence of a hydrogen atom in the tetraflate group facilitates monitoring of reactions and characterization of derivatives.

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Phenyl trifluorovinyl sulfide: a radical acceptor for preparation of gem-difluoromethylene compounds

Cited by 17 publications

References 24 publications

Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators

Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators

Difluorophenylsulfanylmethyl Radical and Difluoromethylene Diradical Synthons: gem-Difluoromethylene Building Block

Preparation and Synthetic Applications of Aryl Tetraflates (ArOSO₂CF₂CF₂H)

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Phenyl trifluorovinyl sulfide: a radical acceptor for preparation of gem-difluoromethylene compounds

Cited by 17 publications

References 24 publications

Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators

Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators

Difluorophenylsulfanylmethyl Radical and Difluoromethylene Diradical Synthons: gem-Difluoromethylene Building Block

Preparation and Synthetic Applications of Aryl Tetraflates (ArOSO2CF2CF2H)

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Preparation and Synthetic Applications of Aryl Tetraflates (ArOSO₂CF₂CF₂H)