Enol thioethers formation

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). 

An interesting rearrangement, which appears to be anion-accelerated, takes place in the enol thioether, anion-terminated vinylcyclopropanes of type 14. ° The rearrangement proceeds at — 78 C and is reasonably stereoselective with regard to the final cyclopentene products (syn selectivity 16 1). Regioisomers are encountered in the formation of the dihydrothiopyran cycloaddition adducts 13 in several instances. The mechanism of this rearrangement appears to involve the enol thioether anion in accord with the well-documented donor acceptor principles " and may be related to similar rearrangements observed with trimethylsilyl enol ether terminated vinylcyclopropanes under fluoride ion or Lewis acid catalysis." " ... 

Another technique is to block one of the a-positions by introduction of a removable substituent which prevents formation of the corresponding enolate. Selective alkylation can be performed after acylation with ethyl formate and transformation of the resulting formyl (or hydroxymethylene) substituent into a group that is stable to base, such as an enamine, an enol ether or an enol thioether. An example of this procedixre is shown in Scheme 1.16, in the preparation of 9-methyl-1-decalone from rra 5-1-decalone. Direct alkylation of this compound gives mainly the 2-alkyl derivative, whereas blocking the 2-position allows the formation of the required 9-alkyl-1-decalone (as a mixture of cis and trans isomers). 

It also appears that thiol pyruvate can serve as sulphur donor for some biological transsulphurations. The thiol nucleotides which occur in small quantities in certain nucleic acids appear to derive their sulphur, at least in part, from thiol pyruvate rather than directly from cysteine. While these reactions have not been extensively studied as yet, ATP is required possibly to activate a group for intermediate thioether formation. Pyruvate elimination could then proceed through an enolate or an intermediate enzyme-bound Schiff base. 

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). ... 

In contrasi to many acetylenes RCsCH, chloroacetylene can be successfully coupled with ketones in liquid ammonia via the lithium compound [80,85], The excellent yield in the reaction with acetone indicates that practically no formation of enolate occurs. Similar good results have been obtained with lithiated ethynyl thioethers, (LiCsCSR), lithiated enyne thioethers, (LiCsCCH=CHSR), lithiated 1,3-diynes (RC=CC=CLi), and lithiated aiylacetylenes (LiCsCAryl)[2], A possible explanation for the small extent of enolization of the ketone is that all these acetylides are less basic due to some stabilization of the anion. 

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... 

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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