Thioacetal monoxides

Oxidation of a thioacetal at one of the sulfur atoms offers some useful features. After formation of the carbanion and addition to an elcctiophilic partner, the hydrolysis is easier than for dithioacetals and can be made with dilute sulfuric or perchloric acid. Moreover, the addition of a lithiated carbanion derived from these species to enones occurs in a 1,4 rather than a 1,2 manner (the usual way for less stabilized more reactive thiocarbanions). The chemistry of these thioacetal monoxides was developed in the 1970s mainly by Ogura and Tsuchihashi [287-290] and by Schlessinger and coworkers [291-293], Two examples of application are given. 

A synthesis of c/v-jasmone [293] illustrates the Michael addition to methyl vinyl ketone of a stabilized carbanion and the hydrolytic step with a protonic acid. 

In the synthesis of a-amino acids [290] through addition of the carbanion of MMTS to nitriles the overall process involves three other steps frequently encountered in sulfur-mediated chemistry a Pummerer-type rearrangement, with a less common migration of a melhylthio group, and a Raney nickel desulfurization following transesterification of the thioesler function. 

MeOH AcNH r—J—COaMe SMe Raney nickel AcNH R-j— COaMe H 

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Hermann and colleagues218,219 found that treatment of ketene thioacetal monoxides 172 and 173, with enamines, sodium malonates, /J-dicarbonyl compounds and lithio-... 

Ketene dimethyl thioacetal monoxide, 6, 311 312. Convenient preparation1 ... 

Schlessinger has shown that the addition of ester enolates to sulfur stabilized acceptors, e.g. ketene di-thioacetal monoxide (151) and methyl a-(methylthio)acrylate (187), is highly efficient for the synthesis of Y-ketoesters.148 Similarly, Ahlbrecht and Seebach have reported that amide and ester enolate additions to nitrogen stabilized acceptors, e.g. nitroalkenes (40) and 2-(/V-methylanilino)acrylonitrile (59 Scheme 72), are highly efficient.149... 

In addition to alkylation of enamines with a-halocarbonyl compounds (Scheme 10), 1,4-dicarbonyl compounds and derivatives may also be prepared by propenylation of enamines followed by ozonolysis , propynylation followed by hydration and reaction with ketone thioacetal monoxide , diethyl 3-bromopropene phosphonate ° and dichloroacetaldehyde oxime (Scheme 21). 

The syntheses by Ban and co-workers of both Na-acetylaspidospermidine (180) and deoxylimapodine (181) (Scheme 32) utilize the important pentacyclic ketone (182), prepared earlier. The critical stage in both syntheses is a Michael reaction, apparently stereospecific, of (182) with methyl vinyl sulphone [-> (180)] and keten thioacetal monoxide [—>(181)], respectively. The later stages in the synthesis are unexceptional. Mercuric acetate oxidation of deoxylimapodine enabled the first synthesis of iVa-acetylaspidoalbidine (183) to be completed. ... 

The terminally oxygenated two-carbon side chain was inserted by Michael addition of ketene thioacetal monoxide to the now familiar vinyl-ogous amide 428 followed by deacetalization to give the aldehyde 447 in 75% yield. In fact, the intermediate 448 existed as two separable isomers, but because each was converted to 447, they were assumed to be isomers at C-18. 

Thermal [2,3] sigmatropic rearrangement of the sulphonium ylide (114) gives a 54% yield of a mixture of four isomeric products, the major (70%) of which is the allenic thioether (115), a species which contains the entire artemisyl carbon skeleton hydrolysis with mercuric chloride then leads to artemisia ketone in 80% yield. The second route involves methallylation of the methyl thioacetal monoxide (116), the unstable intermediate (117) on distillation being transformed into the trienic sulphide (118). The latter species on hydrolysis gives artemisia ketone in 57% yield. 

The first examples of the use of the Knoevanagel-type condensation for the synthesis of a,p-unsaturated sulfoxides were made by Ogura and Tsuchihashi, who prepared racemic ketene thioacetal monoxides by the condensation of methyl... 

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