Dithioacetal monoxides

Treatment of the optically active formaldehyde dithioacetal monoxide with ethyl benzoate in the presence of sodium hydride gives the benzoylated product as a diastereomeric mixture in a thermodynamically controlled (65 35) ratio66. 

The anions of alkyl alkylthiomethyl sulphoxides have found a much broader application. Methyl methylthiomethyl sulphoxide 324 was first introduced by Ogura and Tsuchihashi in 1971412 and ethyl ethylthiomethyl sulphoxide 325 was synthesized by Schlessinger and coworkers in 1973413. Ogura and Tsuchihashi performed alkylation of 324 and obtained a series of substituted dithioacetal monoxides 326 which were then hydrolysed to the corresponding aldehydes (equation 181 Table 17)412. 

TABLE 21. Addition of dithioacetal monoxide lithium salts 376 to cyclic g, /1-unsaturated ketones... 

Dithioacetal monoxide anions react with carbonyl compounds in a similar way affording the corresponding a-hydroxy aldehyde dithioacetal oxides 428. Ogura and Tsuchihashi, who performed this reaction for the first time using the anion of methyl methylthiomethyl sulphoxide 324, obtained in this way a series of a-hydroxyaldehydes 429504 (equation 257). 

The use of ethyl ethylthiomethyl sulphoxide in this reaction leads to the desired addition products in much better yields (95-97%). These products were then converted into ketene dithioacetal monoxide derivatives 430 by a sequence of reactions (equation 258)505. Reaction of 2-lithio-l,3-dithiane-l-oxide with benzophenone affords a mixture of the diastereoisomeric tertiary alcohols 431 in a ratio which is temperature dependent (cis trans changes from 3 1 at — 78 °C to 1 1 at room temperature)268. 

Acylation of the anions of dithioacetal monoxides proceeds in a similar way leading to the desired products 470 in 83-92% yield505,542 (equation 281). 

Dithioacetal monoxides undergo Michael addition to acrylonitrile. The addition products are easily converted into y-ketonitriles 382 (equation 221). Benzenesulphinyl allylic carbanions 383 derived from the corresponding allylic sulphoxides react selectively at the y-position with a variety of cycloalkenones to give the l,4-adducts " (equation 222). Recently, Nokami and coworkers have synthesized some prostaglandin analogues via a three-component coupling process involving 1,4-addition of phenylsul-phinyl allylic carbanion (equation 223) . ... 

The Knoevenagel condensation of a-lithiosulphoxides with hemiacetal 437 has been used to synthesize PGI2 analogues 438 (equation 261). The Knoevenagel-type condensation of dithioacetal monoxides with substituted benzaldehydes has been performed using Triton B as a base and gave the corresponding ketene dithioacetal monoxides 4395 2,513 (equation 262). 

This procedure has been recently applied to the synthesis of L-lyxitol and the polyhydroxylated chain of amphotericin Interesting results have also been obtained in the reduction of ) -oxo derivatives of dithioacetal monoxides. In the reaction sequence of equation 322 two successive asymmetric inductions are involved. After the first reaction, involving acylation of the carbanion, a diastereoisomeric mixture in a 65 35 ratio is produced. When this mixture is reduced with NaBH4 in MeOH-conc. aqueous solution of ammonia, among four possible diastereoisomeric alcohols, the stereoisomer 523 is obtained with a stereoselectivity of 98% . Guanti and coworkers have found that the LiAlH4 reduction of the same substrates at — 78° in THF/ether leads to 523 with a stereoselectivity 99 i6i3.6i4... 

Schlessinger and coworkers described a conjugate addition of enolate species to ketene dithioacetal monoxides (equation 357). Some of the products obtained were elaborated to dihydrojasmone , prostaglandins and rethrolones . 

The adducts of ketone enolates to various a2-synthons, e.g. a-nitroalkenes (40), vinyl sulfoxides, 2-(N-methylanilino)acrylonitrile (59) and ketene dithioacetal monoxide (151), are versatile synthetic inter-... 

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 synthesis of a drug using a dithian as an acyl anion equivalent Dithioacetal monoxides Protected Cyanohydrins of Aldehydes... 

Pummerer rearrangement of 4-benzenesulfinyl-l-naphthols generates naphthoquinone phenylsulfonium ions. These react with enol ethers to afford annulated furanyl ethers. Another Pummerer rearrangement on aryl substituted ketene dithioacetal monoxides provides 2-methylthiobenzothiophenes. ... 

Sulfines provide dithioacetal monoxides in the addition reaction. A controlled reaction can avoid attack on the carbonyl group. 

Practical and diversity-oriented synthesis of multi-substituted benzo[lr] furans was accomplished from simple phenols through a Pummerer annula-tion/cross-coupling sequence. Operationally simple and rapid reactions of phenols with ketene dithioacetal monoxides with the aid of trifluoroacetic anhydride provided the corresponding 2-methylsulfanylbenzo[ ]furans (14BCJ1349). 

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]. 

An alternative approach to benzo[Z ]thiophene derivatives includes treatment of an aryl-substituted ketene dithioacetal monoxide 188 with trifluoromethanesulfonic anhydride [99] (TfjO) in the presence of K2CO3 in toluene at 25 °C, followed by addition of ethanolamine to the reaction mixture, provided benzo[fc]thiophenes, including 3-trifluoromethylbenzo[Z ]thiophene 189, in good yields. The cyclization proceeded through formation of reactive sulfonium electrophile [1(X)]. The synthesis of the starting material 188 was also facile and scalable, starting from aryl ketone 186 and formaldehyde dimethyl dithioacetal S-oxide (FAMSO) [101]. 

Yoshida S, Yorimitsu H, Oshima K (2007) Synthesis of benzo[7>]thiophenes by cyclization of arylketene dithioacetal monoxides under Pummerer-fike conditions. Org Lett 9 5573—5576... 

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