Vinyl thioethers, formation

Examples of the behavior of other substituted vinyl substrates upon exposure to the action of trifluoroacetic acid and triethylsilane are known. For example, -butyl vinyl ether, when reacted at 50° for 10 hours, gives -butyl ethyl ether in 80% yield (Eq. 65).234 In contrast, -butyl vinyl thioether gives only a 5% yield of n-butyl ethyl sulfide product after 2 hours and 15% after 20 horns of reaction.234 It is suggested that this low reactvity is the result of the formation of a very stable sulfur-bridged carbocation intermediate that resists attack by the organosilicon hydride (Eq. 66). 

The intermediates 8 are formed stereoselectively and have the (Z)-configuration. This stereoselectivity has been exploited in syntheses of naturally occurring vinyl thioethers (82JOC374). Other useful synthetic applications of the reaction include those leading to the formation of the cyclic enol... 

Azine approach. Cyclization by oxidative formation of the S—N bond is frequently the final step in isothiazole syntheses. This approach can be used in the synthesis of the parent cation from the thioformyl precursor (129). 2-Substituted derivatives would require thioketone precursors and such compounds are more readily available as vinyl thioethers, e.g. (130). Bromine is used for the oxidative cyclization in this instance giving (13lj (73CC150). 

As with C-N couplings, C-0, C-S, and C-P bond formations also require a Cu(I) or Cu(II) source, a base, and solvent, with reaction temperatures ranging from 45 to 195°C. Typically the couplings see CoupUn are performed with aryl/vinyl boronic acids and aryl iodides (Scheme 3). Use of microwave technology allows for aryl thioether formation between aryl bromides and thiophenols. Inclusion of external ligands is not required for coupling, although several have... 

In 2013, Lei s group described an elegant methodology that utilizes the in situ formation of o-quinolinone quinone methide from suitable precursor under physiological conditions. The in situ-generated methide reacts with vinyl thioethers as electron rich dienophile in hetero-Diels-Alder reaction. This chemistry was successfully used for live cell imaging [78]. 

Use of the methylsulphinyl carbanion as base is recommended for the synthesis of ethers from alcohols and alkyl halides. The catalysed formation of dimethyl ether from hydrogen and carbon dioxide has been reported. Carey has described the use of the silicon-modified organolithium reagent (73) in the preparation of vinyl thioethers (Scheme 151). In order to extend the scope of this reaction to include vinyl ethers themselves, an attempt was made to metalate trimethylsilylmethyl ether use of n-buty 1-lithium resulted in nucleophilic attack on silicon, whereas t-butyl-lithium abstracted the wrong proton, as shown in Scheme 151. 

In contrast to oxygen, sulfur has been far less widely used as a nucleophile for addition to ruthenium vinylidenes. The formation of vinyl thioethers from the addition of thiols to aUcynes catalyzed by binuclear ruthenium complexes Cp Ru (p-SR)2RuCp (R=Et, i-Pr, f-Bu) and related complex Cp Ru(p -C6F5)(p-S) (p-SC6F5)RuCp has been described [112]. 

SYNTHESIS OF VINYL THIOETHERS AND RELATED COMPOUNDS THROUGH THE FORMATION OF SULFUR-CARBON(sp2) BONDS... 

Paris, France) for the treatment of vancomycin-resistant bacteria. A recent synthetic approach by Moreau and Campagne highlighted the intermolecular palladium-catalyzed crosscoupling strategy using vinyl iodide 434 and thiol 435 in an efficient synthesis of the nine-membered core 437 of griseoviridin,whereas the previous total synthesis by Meyers et al. employed the thioether formation 440 by an enolate chemistry of (3-keto ester 438 with a 5-phthalimdo compound 439 to introduce the sulfur moiety (Scheme 46.49). ... 

Thiol-yne radical reactions follow a similar initiation step to that of thiol-ene reactions. After the initial addition of a thiol to the alkyne and formation of a vinyl radical with a P-thioether function, a hydrogen abstraction from another thiol molecule generates a new thiyl radical. Subsequent addition of a thiyl radical on the vinyl thioether forms another carbon radical, which abstracts a hydrogen from another thiol molecule to give a 1,2-dithioether, and the thiyl radical generated reenters the chain process (Scheme 1.11). The addition of the first thiol to the alkyne is the rate-limiting step, and the second thiol addition to the intermediate thiol-alkene is a faster step. Studies revealed that the second addition is approximately three times faster than the first addition [45]. 

Gerber R, Freeh CM (2012) Alkyne hydrothiolation catalyzed by a dichlorobis (aminophosphine) complex of palladium selective formation of cis-conflgured vinyl thioethers. Chem Fur J 18(29) 8901-8905... 

Catalytic hydrogenation with platinum liberates the hydrocarbon from methylcobalamin (57) and from alkyl-Co-DMG complexes (161), but not from pentacyanides with primary alkyl, vinyl, or benzyl ligands, though the cr-allyl complex yields propylene (109). Sodium sand gives mixtures of hydrocarbons with the alkyl-Co-salen complexes (64). Dithioerythritol will liberate methane from a variety of methyl complexes [cobalamin, DMG, DMG-BF2, G, DPG, CHD, salen, and (DO)(DOH)pn] (156), as will 1,4-butanedithiol from the DMG complex (157), and certain unspecified thiols will reduce DMG complexes with substituted alkyl ligands (e.g., C0-CH2COOH ->CH3C00H) (163, 164). Reaction with thiols can also lead to the formation of thioethers (see Section C,3). 

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

The formation of enol ethers and thioethers via coupling between a vinyl bromide and a tin alkoxide or thioalkoxide has been reported by Rossi et al. [205J. Two detailed papers [206,207] have appeared concerning the formation of tertiary aromatic amines via coupling of Bu3SnNMe2 and aromatic systems mechanistic studies are reported. 

Racemic 4-acetoxy-3-unsubstituted azetidinone 10 and homochiral (3R,4R)-3-(IR)-hydroxyethyl derivative 11, commercially available intermediates industrially prepared by the so-called CSI route , testify to the importance of this ring formation strategy. By using vinyl acetate as the olefin partner in the chlorosulfonylisocyanate-alkene cycloaddition, in 1974, Clauss et al. [10] laid down the basis of this approach in the field of p-lactam antibiotics. The most recent efforts have been directed to the key intermediate 11 and its synthetic equivalents 12, 13. Starting from methyl 3R-hydroxybutyrate [11], three independent methodologies have been realized, the main difference being the type (ether, thioether, ester) of enolate used. 

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