Reactions of enethiolates

Again for synthetic applications, thio- and dithioesters are particularly useful. Their enethiolates are easily generated [120]. Potassium and lithium amides and LDA can be conveniently used, and deprotonate the dithioesters quantitatively in THF at -78°C. Methyllithium under the same conditions also acts as a base and not as a nucleophile, and it has the advantage that its conjugate acid is the totally inert methane. 

The enethiolates (2) present interesting aspects. Some are mentioned below (see [120] for a discussion and appropriate references)  

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The addition reaction of enethiolates towards Michael acceptors has been investigated (for reviews, see [120, 362]). It was established that lithium dithioester enethiolates undergo regioselective 1,4-addition with a wiik ... 

When R is an alkyl group, the 3-oxodithioesters available through sulfhydrolysis of the acylation products could not be prepared either by direct condensation of carbon disulfide on a ketone or via oxidation of the P-hydroxy dithioesters formed in the aldolization reaction of enethiolates (see Section 4.2.4). 

The reaction of enethiolates 1425 with halogenoacetylenes, such as bromobenzoylacetylenes and ethylthio(chloro)-acetylene, lead to functionally substituted pyrrolothiazolidines 1426 in 37-85% yields (Scheme 274) <2002CHE86, 2002SUL87>. 

There appears to be little reported work on S-nitrosation reactions of simple thioke-tones. Thiocamphor when treated with /50-amyl nitrite in fact gives the oxime58 (formerly called a isonitroso compounds), presumably via the tautomeric form of the thione, i.e. the enethiol. In this respect the reaction is very similar to the reactions of ketones59 which give oximes or C-nitroso compounds via the enol intermediates60. 

An interesting variation of the Dieckmann cyclization involves vinylogous activation of a methyl group in a 2-butenyl ester. Reaction of an a-halo ester with the enethiol formed by treatment of an acetoacetic ester, which may be substituted at the a-position, with hydrogen sulfide produces (92) in satisfactory yield. Treatment of these compounds with sodium in benzene produced the 4-hydroxythiophene-2-acetic acids (94) (40JCS1385). The product undoubtedly involved the intermediate (93), in which the activated methyl goup has condensed with the ethoxycarbonyl group in typical Claisen fashion. 

However, for aliphatic low-molecular-weight members of this class, oligomerization and/or polymerization, formation of gem-dithiols and enethiolization are often observed. The purification steps can be tedious and the obtention of pure products difficult. There is still a need for progress in this field. Although much less used, another general method whose scope appears important [127] involves the reaction of ketimine... 

A good stereospecificity has also been demonstrated for the reaction of m-enethiolates with aldehydes [359,360]. 

Aliphatic thioketones result tautomerically pure from the reaction of H2S with ketals in the presence of ZnCl2. Deprotonation with LDA gives the enethiolate which can be silylated to form the silyl vinyl sulphide. These are fairly stable to traces of water but react with MeOH to give the enethiol (equation 3)7. 

For both reactions the yields of the enethiolate ions are better than 95% small amounts of HF7V thioenolate cluster ions were also observed182,183. The results of some acid-base and exchange chemical studies of enethiolate anions are summarized in Table 25. 

In some cases it is the diene component from the retro reaction which is the desired product and extrusion of a volatile alkene such as ethylene is then ideal. Pyrolysis of the 1,4-oxathiin systems 21 proceeds in this way to give the a-oxothiones 22 which for R = Pr1, exists mainly as the enethiol tautomer 2323. Thermal extrusion of ethylene from 24 provides convenient access to the interesting fulvene 25 in quantitative yield24, and the corresponding reaction of 26 at 650 °C and 10-4 torr gives the cyclopentadienoben-zopyrene 28 in 95% yield, presumably by way of the intermediate 2725. 

The main class of electrophiles which reacts on the sulfur atom of enethiolates are alkyl halides. This was applied by Vallee and Tchertchian [121] in a one pot synthesis of hydroxy-ketenedithioacetals which elegantly uses the preceding features. Deprotonation of alkyl dithioacetates by LDA at -78 °C provided enethiolates which were treated by aldehydes. Comparable to the case of enolates, the aldol reaction takes place on the carbon atom. When water is added to the reaction mixture, 3-hydroxyalkanedithioates are obtained. However, if the quench is replaced by an alkyl halide addition, hydroxyketenedithioacetals are obtained. Formation of these compounds... 

An arylation reaction of potassium thioamide enethiolates was achieved in good yield by treatment with aryl iodides in the presence of FeBr2 or with photochemical irradiation, perhaps through an SRN1 mechanism [122]. 

The aldol reaction of dithioester enethiolates has been used for the synthesis of dithiolactones [123], chiral substrates for the Claisen rearrangement [124, 125], and oxathianes [126]. Thioamide enethiolates may be employed in this reaction as well as shown with /Tthiolactams [26], or with a precursor of the antitumour agent vinblastine [127]. 

Amination of enethiolates has only been recently tackled by Beslin and Marion [136] and Hartke et al. [137]. Silylketene dithioacetals or lithium enethiolates react with azodicarboxylates to yield a-hydrazino-dithioesters, thionoesters or thioamides. Homologous dithioesters, bearing an amino moiety on the f5 position, have been prepared from the reaction of silylketene dithioacetals with an imine in the presence of a Lewis acid [138]. 

The reaction of thiocyclopropanoyl dimethylphenylsilane lh with organolithium reagents takes a deviant course as a result of enethiolization, and the initially formed enethiolate is trapped in the presence of methyl iodide29 (Scheme 10). 

It is interesting to note that nonsilylated enethiols have only been prepared as mixtures with their isomeric thioketones.4a,c The first selective synthesis of aliphatic enethiols was performed by Metzner52 by deprotonation of enethiolizable thioke-tones 42 with LDA and reaction of the enethiolates with trimethylsilylchloride. The subsequent methanolysis of silyl vinyl sulfides 43 afforded enethiols devoid of isomeric thioketones. Treatment of the enethiolates with various proton sources afforded instead mixtures of thioketones and enethiols (Scheme 31). 

Roush, W. R. The catalytic asymmetric Michael reaction of tin(ll) enethiolates. Chemtracts Org. Chem. 1988,1,439-442. 

In 1988, Mukaiyama et al. reported the Sn(OTf)2-50d-catalyzed asymmetric Michael reaction of a trimethylsilyl enethiolate, CH2=C(SMe)SSiMej (up to 70% ee) [243]. It was proposed that the catalytic reaction proceeded via an Sn(II) enethiolate. They also demonstrated that a BINOL-derived oxotitaniurn catalyzes the Michael addition of ketene silyl thioacetals to a-enone with high enantioselectivity (up to 90% ee) [244]. After this pioneering work other research groups developed new reaction systems for enantioselective Mukaiyama-Michael reactions. 

The thieten 1,1-dioxide (48) has been prepared by cycloaddition of an enamine and sulphene at 0°C. Mild thermolysis causes a ready retrocyclo-addition to occur. Additional stable 3-sultines have been isolated, by the reaction of the anion of a sulphoxide with a ketone and cyclization of the resulting j3-hydroxy-sulphoxide with sulphuryl chloride. Treatment of 2-methylthietan (49) with alumina at 150-350 °C results in the formation of tetrahydrothiophen and but-3-enethiol. ... 

The common method involves deprotonation of a thiocarbonyl compound and reaction of the intermediate enethiolate with an allyl halide (Scheme 9.8). This actually relies on two noticeable features of the sulfur series. (1) The proton located a to a thiocarbonyl group is much more acidic, by 7-10 pKa units, than the one of a carbonyl moiety [39, 41]. This may be related to the strong ability of the sulfur atom (polarizability) to stabilize the negative charge of the enethiolate. Presently, the preferred conditions involve LDA as a base for optimum deprotonation [42-45]. (2) The resulting anionic species are soft ambident nucleophiles. The... 

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