Ketene dithioacetals, hydrolysis

The high diastereoselectivity attending the spirocyclisation of ketene dithioacetals provides an effective means for controlling the stereochemistry of a methyl substituent at the a-position on a 6-lactone ring,244 The method was applied to the synthesis of the polyether antibiotic Salinomycin [Scheme 2.120].242 Condensation of the methyl ketone 120 1 with the lithiated l,3-dithian-2-yl-phospho-nic acid diethyl ester 120.2 gave the ketene dithioacetal 1203 in 76% yield. After hydrolysis of the two benzoate ester groups, cyclisation of diol 120.4 was... 

The remarkable feature of this approach is that it could be utilized towards direct, stereospecific a-glycosylation. This was illustrated by addition of sugar alcohols to ketene dithioacetals, promoted by TMSOTf, to reach after oxidative hydrolysis of the dithianyl residue, the corresponding a-disaccharides in high yield [130a], The steric course of the glycosylation reaction, is possibly controlled by the influence of the dithianyl group for the attack of a nucleophile on one side. 

The actual umpolung reaction that allows a ketene dithioacetal to function as if it had an electrophilic carbon a to a carbonyl is achieved by conjugate addition of nucleophiles to the ketene dithioacetal, followed by hydrolysis. Both sulfide and sulfoxide ketene derivatives can be used. Conjugate addition of an ester enol-ate derived from ferf-butyl acetate (secs. 9.2, 9.4.B, 9.7.A) to the ketene dithioacetal [CH2=C(SOMe)2] gave the stable dithioacetal anion (382). Conversion of the dithioacetal to the bis(sulfoxide) enhanced the ability of that species to function as a Michael acceptor. Subsequent transformation of 382 gave the aldehyde-ester (383).370... 

The synthesis of pm-substituted 3,4-diaryl-thienothiophene 120 from (4-MeC6H4CH2)2CO through the corresponding ketene dithioacetal, Dieckmann cyclization, hydrolysis and decarboxylation was described (2000SC1695). 

Acidic hydrolysis of the ketene dithioacetal generates a carboxylic acid. 

Nucleophilic additions to the carbon-carbon double bond of ketene dithioacetal monoxides have been reported [84-86]. These substrates are efficient Michael acceptors in the reaction with enamines, sodium enolates derived from P-dicarbonyl compounds, and lithium enolates from simple ester systems. Hydrolysis of the initiEil products then led to substituted 1,4-dicarbonyl systems [84]. Alternatively, the initial product carbanion could be quenched with electrophiles [85]. For example, the anion derived from dimethyl malonate (86) was added to the ketene dithioacetal monoxide (87). Regioselective electrophilic addition led to the product (88) in 97% overall yield (Scheme 5.28). The application of this methodology to the synthesis of rethrolones [87] and prostaglandin precursors [88] has been demonstrated. Recently, Walkup and Boatman noted the resistance of endocyclic ketene dithioacetals to nucleophilic attack [89]. 

EWG-Activated 2-methylene dithioles (= cyclic ketene dithioacetals with electron-withdrawing substituents) 38 undergo a ring-opening reaction mediated by primary aliphatic amines to give polyfunctionalized 2-(alkylamino) thiophenes (40) after hydrolysis in a one-pot procedure [82] ... 

Lithio-2-trimethylsilyl-l,3-dithiane is the most widely utilized reagent for the conversion of ketones and aldehydes to the corresponding ketene dithioacetals (Scheme 2.49) [126-128]. It is used for the synthesis of functionalized 2-alkylidene-1,3-dithianes 79 [129-135]. The 2-alkylidene-l,3-dithianes 79 thus synthesized are useful synthetic intermediates, which are conveniently accessible by means of Peterson reactions, and they can be transformed into various compounds [136, 137]. For example, compounds 79 are converted to the corresponding carboxylic acids, aldehydes, and enones by hydrolysis, hydrogenation followed by hydrolysis, and deprotonation followed by alkylation and hydrolysis, respectively (Scheme 2.49) [138-140]. 

On the other hand, the reactions of 2-lithio-2-trimethylsilyl-l,3-dithiane with esters and thioesters give not the ketene dithioacetals, but the 2-acyl-l,3-dithianes 81 (Scheme 2.50). The possibly formed silyl enol ethers 80 undergo subsequent hydrolysis to give 81 [141],... 

Ketene- S -acetals, which are useful synthetic intermediates, have been employed in an approach to the highly substituted thiophenes 11, which were obtained in good yields upon treatment of the substrates 12 with primary amines, and subsequent hydrolysis of the resulting intermediate imines to the final acetylated products <07OL4845>. Likewise, arylketene dithioacetal monoxides have been annulated to benzo[6]thiophenes, such as 2-methylthio-3-trifluoromethylbenzo[b]thiophene <07OL5573>. 

The substituted ketene S,S-dithioacetal (76) has been developed as a P-lithioacrylate equivalent (Scheme 22). Deprotonation of (76) leads to an allylic anion (77) that reacts with a wide range of electophiles to give the T-substituted adduct (78), as the only observed product. Hydrolysis of the ketene thioacetal then releases the carboxyl residue, and this activates the system towards elimination of thiophenol, thereby unmasking the acrylate unit. Dianion (79) may also be regarded as a modified B-lithio-acrylate equivalent, but the chemistry of this species is diverse. Not only have B-substituted a, B-unsaturated amides been synthesized, but the same reagent reacts, for example, with epoxides to give ultimately dihydropyrans the species (79) is therefore perhaps more accurately represented as equivalent to the dipolar... 

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