Thioxoester

A new method for the preparation of diethyl thioxomalonate, already prepared from Bunte salts340 (Section m.E.5), has been introduced by Abelman351. In this approach, diethyl chloromalonate was reacted with cesium carbonate in the presence of elemental sulfur to yield the thioxoester which underwent a facile [4+2] cycloaddition (equation 74). 

In the case of /i-thioxoesters, deprotonation with base followed by alkylation gives rise to reaction on the sulfur atom415 (equation 108). 

The enzymatic reduction of a thiocarbonyl compound has been investigated [159] for the first time, in order to provide a new route for enan-tiopure thiols, molecules which are currently needed for asymmetric synthesis. Reaction of easily available /1-thioxoesters with baker s yeast under classical conditions did furnish the expected thiols, but with lower enantiomeric purity and moderate conversion rate, due to the competitive hydrolysis of the thioxo group into a carbonyl leading to an alcohol. However, conditions (ethyl acrylate, dry yeast) were found to improve the production of (S)-ethyl 3-mercaptobutanoate. Cyclic thioxo esters led to high stereoselectivity of cis (1S,2S) products, but with moderate chemical yields. 

Koizumi and his group have published [219] the first attempt to achieve an asymmetric version using 8-arylmenthols as chirality auxiliaries. Enan-tiopure methyl thioxoesters were prepared by reaction of dichloroacetates with (Bu3Sn)2S/TBAF. Cycloaddition to cyclopentadiene led to encouraging results (Table 3, entry 5). 

A stable aliphatic thioacyl chloride (44) was obtained according to equation (42) and used in alcoholysis reactions to prepare thioxo malonates (45)."° A mixture of sulfenyl chloride (46) and trisulfide (47), which does not however contain an a-oxothioacyl chloride, also yields thioxoesters on base-catalyzed reaction with methanol (equation 43). ... 

Thioketenes are stable isolable compounds only if the heterocumulene system is protected against dimerization by bulky substituents or perfluoroalkyl groups. 4 in these cases they are suitable educts for addition of hydroxylic compounds. 4. 4.ii5 reaction is also possible for the ylid (SO). The resulting thioxoester (51) does not however react with p-nitrobenzaldehyde in a Wittig reaction. ... 

Furthermore, transient thioketenes with a wide variety of substituents R and R, including hydrogen, can be generated by flash vacuum thermolysis of l,2,3-thiadiazoles. 4 By in situ reactions thioxoesters are formed with alcohols (equation 47). 

Interconversion of a thioxocarboxylic ester with an alcohol can be achieved in the presence of a base. The reaction takes place with high yields if amino alcohols or diols are used. A series of macro-cyclic polyether thioxoesters has been prepared by treating (9,(9 -diethyl dithiooxalate and 0,0 -dimethyl 2,6-pyridinedicarbothioate with glycols. Methanol or ethanol were removed from the equilibrium mixture by distillation or adsorption in molecular sieves (equation 48). ... 

The above-mentioned (9-deoxyribosyl thiobenzoate (c/. equation 39) was obtained from 1,5-protected deoxyribose and phenyl dithiobenzoate. ° Also vinyl arenecarbodithioates were shown to be applicable for the synthesis of thioxoesters." ... 

Sulfhydrolysis of imidates is one of the most powerful tools in the field of thioxoester syn-thesis. 2 2 Advantageously, hydrochlorides or acetates are used as substrates instead of the free bases. Nitriles are useful precursors, but in some cases amides or imidochlorides are preferred as the starting material, according to Scheme 5.6. 4.i5.2s.28... 

This method can be applied with almost every substituent R and R. Thioxoesters of dicarboxylic acids can also be prepared via the imidates. Fully characterized authentic compounds of this type were, however, not obtained until the 1970s. Synthetic problems arise especially if the thioxoester groups are close enough to each other to permit formation of heterocycles during their synthesis. 

In a similar way to the formation of open-chain thioxocarboxylic esters, thioxolactones are obtained from cyclic imidates. Kaloustian et alP have studied this reaction and its mechanism in detail. It is closely related to the sulfhydrolysis of dialkoxycarbenium ions, which also results in the formation of thioxoesters or thioxolactones (Scheme 6). ... 

Dimethyl monothiomaleate (56) and monothiofumarate (57) are formed in a complicated reaction from 2,5-dimethoxythiophene via an intermediate of the orthoester type. 0-Trimethylsilyl ketene-0,0-acetals are readily formed from carboxylic esters and can be transformed to thioxoesters, without being isolated, by reaction with hydrogen sulflde, according to equation (34). Methyl thioxoarachido-nate (58) was prepared by this route. ... 

The interchange reaction between a thioxoester and a thiol does not, in general, represent a meaningful synthetic procedure since dithioesters are more readily available than thioxoesters in most cases. However, 0,S-diethyl tiithiomalonate (61b) and diethyl tetrathiomalonate (61c) were prepared from 0,0-di-ethyl dithiomalonate (61a). On the other hand, the transformation of one dithiocarboxylic ester into another can be a useful and practicable reaction. For instance, ethyl arenecarbodithioates are intercon-verted to 2-dialkylaminoethyl arenecarbodithioates, according to equation (62). 

From thioamides, thioxoesters, thioureas, amides and various reagents... 

The reaction of amine hydrochlorides with thioxoesters affords amidinium salts (155 equation 91). Formamidinium salts (156 equation 92) with bulky substituents at the nitrogens can be obtained by oxidation of AA A/ -trisubstituted or AA -disubstitut thioureas with peracetic acid. - Byproducts in this reaction can be ureas and thiourea trioxides. -Dimethylaminoacrolein reacts with dimethylamine hydrochloride to give (157 equation 93), the parent compound of the vinylogous amidinium salt series. - From AA -dimethylthiobenzamide and Al-sulfinyldimethylammonium tetrafluoroborate the benzamidin-ium salt (158 equation 94) was prepared. ... 

In the Barton-McCombie radical deoxygenation reaction the hydroxyl group of an alcohol is replaced with a hydrogen atom. Even hindered secondary and tertiary alcohols may be deoxygenated by this method. In a typical procedure the alcohol is first converted to a thioxoester derivative, which is then exposed to tri-n-butyltin hydride in refluxing toluene. 

Thiolesters (RCOSEt) are reduced to alcohols by UBH4 in Et20 or by an excess of n-Bu4NBH4 in refluxing CHCI3, but are inert in the presence of borane [KH5, LL4]. Dithioesters and thioxoesters are reduced to thiols by BH3-Me2S [JS4]. 

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