Enol thioethers

These compounds typically react with electrophiles on carbon and in this respect they resemble enamines, enol ethers and enol thioethers. For example, both pyrrole and 1-pyrrolidinocyclohexene can be C-acetylated (Scheme 4). 

If an aldehyde or ketone possesses an a hydrogen, it can be converted to the corresponding enol thioether by treatment with a thiol in the presence of TiCU ... 

For references to the use of the Wittig reaction to give enol ethers or enol thioethers, which are then hydrolyzed, see Ref. 58, pp. 715, 726. 

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 comparison of thiophene with thioethers on the one hand and with enol thioethers on the other, in regard to its behaviour towards conventional electrophiles, has been made in Section 3.02.2.3. Attack on carbon is the predominant mode of reaction (Section 3.14.2.4) reaction at sulfur is relatively rare (Section 3.14.2.5). Carbenes are known to act as electrophiles attack at both carbon and sulfur of thiophene has been reported. The carbene generated from diazomalonic ester by rhodium(II) catalysis attacks the sulfur atom of thiophene, resulting in an ylide. It has also been shown that the carbenoid species derived by thermolysis of such an ylide functions as an electrophile, attacking the a-carbon of a second molecule of thiophene (Section 3.14.2.9). Singlet nitrene is electrophilic. However, in contrast to carbenes, it invariably attacks only the carbon atom (Section 3.14.2.9). 

Cyclizations of alkenic amines and imines using organoiron complexes to generate bicyclic 3-lactams are discussed in Chapter 3.1 of this volume. Examples of heterocyclizations of alkenic NA/-dialkylamine and pyridine derivatives to form cyclic quaternary ammonium salts are cited in the Staninets review.Ic A cyclization of an enol thioether has been used to generate a thiazolidine intermediate used in cephalosporin synthesis (equation 131).262... 

Phenylthiotrimethylsilane adds to propenoyl trimethylsilane under the influence of Lewis acid to give l,3-bis(phenylthio)-l-trimethylsilylprop-l-ene (18). This enol thioether may be deprotonated with f-butyl lithium and alkylated with any of a large range of electrophiles. Subsequent hydrolysis-elimination with mercuric chloride in aqueous acetonitrile provides -substituted a,/J-unsaturated acyl silanes (vide supra, Section III.D.3)132. It should be noted that, in this transformation, the /1-substituent has... 

The adducts of 1-arylthiocyclopropyllithium 116 61) to aldehydes and ketones, upon treatment with p-toluenesulfonic acid in refluxing benzene under anhydrous conditions or with the Burgess reagent67), underwent ring expansion to 1 -phenylthiocyclobutenes, which may be hydrolyzed to cyclobutanones, desulfurized to cyclobutanes or thermo-lyzed to dienes. Thus, the cyclopropylcarbinol 233, adduct of 116a to /-butyl methyl ketone, was rearranged to the cyclobutanone enol thioether 234, Eq. (72) 139). 

Acetoxylation of enol thioethers. The reaction of enol thioethers with lead tetraacetate (1,1 equiv.) in THF for 1 hour followed by addition of BFj etherate (or 5 N KOH-ether) results in allylic acetoxylation. The reaction is considered to involve bisacetoxylation of the double bond. Oxidation of sulfur is not observed. Examples ... 

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." " ... 

The synthesis of a topical anti-inflammatory, anti-allergic agent that is inactivated in the bloodstream starts with the scission of the dihydroxyacetone side chain of the corticosteroid fluoroprednisolone (34-1) (see Chapter 7, Scheme 7.17) with sodium bismuthate (Scheme 5.34). Reaction of the product, 34-2, with methanethiol affords the thioacetal 34-3. The acetal extrudes one of the thiomethyl groups under acidic conditions to form the enol thioether 34-4. Treatment of that product with ethanethiol restores the thioacetal (34-5). The stereochemistry at Cu is defined by addition of ethanethiol from the more open backside of the thioenol 34-4. 

The sterically relatively open carbonyl group at C3 is significantly more reactive than its hindered counterpart at 20-Reaction of 16-dehydroprogesterone (1-4) with benzenethiol takes a different course at the two conjugated ketones present in the compound. Reaction at C3 proceeds to form an enol thioether reaction with the unsaturation in ring D, on the other hand, consists of conjugate addition of the thiol at a distance from the hindered carbonyl (6-1) (Scheme 6.6). 

Enol Ethers and Enol Thioethers Acetals and Ketals as Precursors of Enol Ethers. 367... 

Direct hydrolysis of the enol thioether function in (2) and (3) proved unexpectedly difficult however, it was possible to hydrolyze the free acid (4) by 1 1 HCl-HOAc at 90° to give (5), which contains a masked aldehyde group. This substance undergoes a normal Wittig reaction with carbomethoxymethy-lenetriphenylphosphorane to give (6). 

Beckmann fragmentation. Autrey and Scullard have shown that Beckmann fragmentation rather than Beckmann rearrangement is favored by introduction of a methylsulfenyl group a to the oxime group in addition, the termini of the bond that is cleaved are obtained in different oxidation states. Thus cleavage of the oxime of 2-methylthio-7-methoxytetralone-l (4), prepared as shown, leads to approximately 1 1 mixtures of the enol thioethers (5) and (6). 

Autrey and Scullard used this fragmentation in a synthesis of corynantheine (11) from yohimban-l7-one (7). The synthesis also involved a novel desulfurization of the enol thioether (9) without reduction of the vinyl group. This step... 

The reaction can be applied to silyl enol esters as well. Good asymmetric induction can be achieved in the Mukaiyama aldol reaction. The reaction of silyl enol thioether 246 and nonanal, for example, gave 247 in 60% yield and in 93% ee when the (/ )-BINOL-titanium catalyst shown was used. In this work, the reaction was also done in supercritical fluoroform and in supercritical carbon dioxide. A similar reaction was reported using catalysts closely related to 244 and dichloromethane as the solvent.Chiral oxazaborolidine catalysts have also been shown to be effective for enantioselective Mukaiyama aldol reactions. 

P-ffeto esters tt-methylene ketones The anhydride (1) undergoes Diels-Alder reactions with dienes at 0-80° to give only endo-adducts usually only one of the two possible cnrfo-adducts is formed. The double bond in the adducts can be reduced without desulfurization with H2 and PdfOH) on carbon. The adducts are convertible by oxidative decarboxylation with NCS (6, 116-117) to the ketal and/or the enol thioether of a j3-keto ester, both of which are hydrolyzable to... 

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). 

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