Radical-mediated thiodesulfonylation of the vinyl sulfones: access to (α-fluoro)vinyl sulfides

Abstract

Radical-mediated thiodesulfonylation of the vinyl and (α-fluoro)vinyl sulfones, derived from aldehydes and ketones, with aryl thiols in organic or aqueous medium provided access to vinyl and (α-fluoro)vinyl sulfides. The vinyl sulfides were formed predominantly with E stereochemistry independent of the stereochemistry of the starting vinyl sulfones. KeywordsFluoroalkenes; Radical reactions; Vinyl sulfides; α-Fluoro vinyl sulfides; Vinyl sulfones Vinyl sulfides are valuable tools in organic synthesis and are used as enolate ion equivalents, 1 as components of [2+2] cyclo-additions, 2 and as substrates in transition metal catalyzed carbon-carbon bond forming reactions.3 Methods for the synthesis of 1-alkenyl sulfides include Wittig reaction,4 ionic and radical additions of thiols to alkynes,5 coupling of 1-alkenyl halides with thiols, 6-9 and transition metal catalyzed anti-Markovnikov hydrothiolation 9-12 of alkynes with arenethiols and alkanethiols to produce E isomers, including hydrothiolation in water medium. 13 Vinyl sulfonium ions, generated via the biological methylation of the corresponding vinyl sulfides act as inhibitors of thioether S-methyltransferase 14 and proteolytic enzyme papain. 15 They are highly reactive towards nucleophiles and bind covalently to DNA, RNA and proteins in vivo. 16 Moreover, vinyl sulfonium salts are more electrophilic than the corresponding vinyl sulfones, which are known for their ability to inhibit cysteine proteases. 17,18 The (α-halo)vinyl sulfides can be prepared by Wittig-Horner reactions with diethyl chloro (phenylthio)-methanephosphonate 19 or by addition of the hydrogen halides (HI, HBr and HCl) to acetylenic sulfides (chalcogenides).20 The regioselectivity and stereoselectivity of such additions were improved when equivalent quantities of hydrogen halide, generated in situ from trimethylsilyl halides and anhydrous methanol, were utilized 21 instead of excess aqueous HX or saturated gaseous HX in benzene. The (α-halo)vinyl sulfides have been employed in Stille, 21, Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Herein, we report stereoselective radical-mediated thiodesulfonylations of vinyl and (α-fluoro) vinyl sulfones with aryl thiols to provide access to vinyl and (α-fluoro)vinyl sulfides. Such thiodesulfonylation provides a flexible alternative to the hydrothiolation of alkynes with thiols under radical or metal catalysis conditions. It also offers convenient preparations of (α-fluoro) vinyl sulfides -a class of interesting fluoroalkenes which remain unexplored. 34 The thiodesulfonylation can be also viewed as re...

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

“…63 As these initial assays were conducted with racemic inhibitor, we first set out to resolve the individual antipodes of α-(1′-fluoro)vinyllysine. Pleasingly, it was discovered that this quaternary, α-fluorovinyl AA could be selectively benzoylated at the ε-amino group under Schotten-Baumen conditions.…”

Chemoselective Synthesis of Unsymmetrical Internal Alkynes or Vinyl Sulfones via Palladium‐Catalyzed Cross‐Coupling Reaction of Sodium Sulfinates with Alkynes

“…( E )‐1‐[2‐(Phenylsulfonyl)vinyl]‐4‐(trifluoromethyl)benzene (3bk): 26 Yellow oil; 1 H NMR (400 MHz, CDCl 3 ): δ =7.97–7.95 (m, 1 H), 7.54 (m, 9 H), 6.96 (d, J =15.5 Hz, 1 H); 13 C NMR (100 MHz, CDCl 3 ): δ =140.4, 140.2, 135.7, 133.7, 130.1, 129.5, 128.7, 127.8, 126.1, 126.0; IR (KBr): ν =3064, 2925, 1613, 1383, 1325, 1169, 1120, 1067, 845, 750 cm −1 ; MS (EI): m / z =312, 247, 187, 159, 125, 97.…”

Fluorovinyl Thioethers as Putative Steric and Electronic Thioester Enolate Mimetics: Chemoselective HF Addition to Acetylene Thioethers

“…The detailed procedures for the synthesis of compounds 4a, 4b, 4c, 3, 5, 6, 10, 11, and 12, as well as the 1 H, 19 F, and 13 C NMR spectra for all compounds, are available on the Journal's website.…”

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