Metalation dithioacetals

Metalated dithioacetals are known to be useful as acyl anion equivalents. Thus, successful diastereoselective reactions have led to many applications of dithioacetals [63]. However, only a few enantioselective reactions of symmetric dithio-... 

A series of reagents have been developed which are prepared in situ from a geminal dihalide or a dithioacetal [635,730] and a transition metal complex. Titanium-based reagents of this type olefinate a broad range of carbonyl compounds, including carboxylic acid derivatives (Table 3.12), and are a practical alternative to the use of isolated carbene complexes. 

It is difficult to obtain cross-coupling products of two different carbonyl compounds by an intermolecular version of the McMurry reaction. Examples that use excess amounts of one carbonyl component are few. "" When one carbonyl component is replaced by a 1,1-dihalo compound or dithioacetal and the alternative is reduced with a low-valent metal such as low-valent titanium or chromium(ii), cross-coupling products, that is, Wittig-type olefins, are produced in high yields. Because the alternative approach is described elsewhere, we concentrate on only its important features here. 

We have discussed previously (see Section 2.4) some aspects of the dithioacetalization step involved in this strategy. The presence of the sulfur atoms offers another possibility as a methylene unit results from desulfurization by Raney nickel, dissolved metal or LiAlH4/ZnCl2 reduction [281]. 

Metal-catalysed Grignard reaction with sulfides and dithioacetals... 

Dithioacetals (see also dithianes and dithiolanes) alkylation of 98 as acyl anion equivalents 75 carbanions of 87,97-102 cleavage of 14-18,98,102 desulfurization of 78 metal-catalysed coupling 127 reaction with Grignard reagents 127 reductive lithiation of 89 synthesis of 12-19,97-102 Dithioacids synthesis of 40... 

Cleavage of dithioacetals by clay-supported metal nitrates 15... 

As mentioned in Section 4.2.2.6, dithioacetals can be used in coupling reactions with Grignard reagents in sequences leading to the formation of carbon-carbon single and double bonds. The metal-catalysed reactions depicted here exemplify their uses for olefination reactions, which opened the way to many useful synthetic applications [319],... 

Dithioacetic acid, phenyl-metal complexes, 646 Dithiobenzoic acid metal complexes, 646 colours, 646 Dithiobiuret metal complexes, 640 Dithiocarbamic acid metal complexes, 585 Ditbiocarbazic add metal complexes, 803 Dithiocarbimic acid metal complexes, 588 Dithiocarbimic acid, cyano-metal complexes, 808 Dithiocarboxylic acids... 

Given the selection of an appropriate substrate, the generation of a carbon centred radical from such a substrate can initiate a series of bond-making and bond-breaking processes which are sometimes referred to as radical cascade reactions. These can be of great synthetic value. Thus, treatment of the ketene dithioacetal 1 with a five fold excess of tributyltin hydride in hot benzene under nitrogen and in the presence of a catalytic amount of AIBN gave the metallated benzo[ fc]thiophene 2, itself a valuable synthetic intermediate, in 70% yield. 

All types of electrophiles have been used with 2-lithio-l,3-dithiane derivatives, including alkyl halides, sulfonates, sulfates, allylic alcohols, arene-metal complexes, epoxides, aziridines, carbonyl compounds, imines, Michael-acceptors, carbon dioxide, acyl chlorides, esters and lactones, amides, nitriles, isocyanates, disulfides and chlorotrialkylsilanes or stannanes. The final deprotection of the dithioacetal moiety can be carried out by means of different types of reagents in order to regenerate the carbonyl group by heavy metal coordination, alkylation and oxidation184 or it can be reduced to a methylene group with Raney-nickel, sodium or LiAIII4. 

Dithioacetals of aldehydes are sources of carbanions and hence may be used to form new C-C bonds in reactions in which the formerly electron-deficient character of the aldehydic carbon has been reversed. The 1,3-dithianes derived from formaldehyde or a higher aldehyde may be metallated and then alkylated (Scheme 2.27). Hydrolysis of the dithioac-etal is usually carried out in the presence of a thiophilic (sulfur seeking) metal salt such as a mercury salt. The insoluble sulfides cause the equilibrium to move in favour of the parent carbonyl compound. 

Hydrogenolysis of the C-S bond can be achieved both by dissolving metal systems (sodium in liquid ammonia) or by catalytic methods, particularly with a finely divided reactive form of nickel known as Raney nickel. When the latter is combined with dithioacetal formation, using either ethanedithiol or propane-1,3-dithiol, the result is a mild method for reducing a carbonyl group to a methylene group. 

The dithiane-derived anion can be generated by the action of Bu°U in THF at -78 C or with complex bases NaNH2-RONa at room temperature. Lithiated dithiane can also be prepared in situ by sonica-tion of n-butyl chloride with lithium in the presence of dithiane. Dithioacetals or ketals are resistant to acidic or basic hydrolysis. Regeneration of the carbonyl group from the dithioketal sometimes presents difficulties but can be carried out by hydrolysis in polar solvents (acetone, alcohols, acetonitrile) in the presence of metallic ions such as Hg , Cu, Ag, 71 177 qj j m ise Alternatively, alkylative hy lysis... 

Whereas free singlet carbenes are rather unselective with respect to formation of cyclopropane 22 or ylide 23 and the cyclopropane is favored under conditions that populate the triplet state of a carbene (see Section I.2.I.2.4.2.6.2.), the metal carbenes generated with copper or rhodium catalysts display a selectivity for functional groups which are more nucleophilic than a double bond. Thus, no cyclopropanes are obtained from dialkylallylamines allyl sulfides -allyl dithioacetals , and allyl selenides under carbenoid conditions (copper or rhodium catalysts). 

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