Ketene dithioacetal monoxides

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. 

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). 

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-... 

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. ... 

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]. 

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>. 

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