Dithioacetals, alkylation from aldehydes

The reaction of aldehydes or ketones with thiols, usually with a Lewis acid catalyst, leads to dithioacetals or dithioketals. The most common catalyst used is probably boron trifluoride etherate (BF3 OEt2). Similarly reactions that use 1,2-ethanedithiol or 1,3-propanedithiolleadto 1,3-dithiolanes, such as 18 or l,3-dithianes. " Dithioa-cetals can also be prepared from aldehydes or ketones by treatment with thiols in the presence of TiCU, SiCU, LiBp4, AKOTfls, with a disulfide RSSR (R = alkyl or aryl), or with methylthiotrimethylsilane (MeSSiMe3). " ... 

In dithioacetals the proton geminal to the sulfur atoms can be abstracted at low temperature with bases such as Bu"Li. Lithium ion complexing bases such as DABCO, HMPA and TMEDA enhance the process. The resulting anion is a masked acyl carbanion, which enables an assortment of synthetic sequences to be realized via reaction with electrophiles. Thus, a dithioacetal derived from an aldehyde can be further functionalized at the aldehyde carbon with an alkyl halide, followed by thioacetal cleavage to produce a ketone. Dithiane carbanions allow the assemblage of polyfunctional systems in ways complementary to traditional synthetic routes. For instance, the p-hydtoxy ketone systems, conventionally obtained by an aldol process, can now be constructed from different sets of carbon groups. ... 

A novel synthesis of cr-diketones from aldehydes proceeds by the formation of the anion of the ethylene dithioacetal of the aldehyde, reaction with Fe(CO)j, alkylation, and hydrolysis. 

Recent work [109, 110, 111] has shown that 1,3-dithian and 2-substituted 1,3-dithians (27) (Le., cyclic dithioacetals derived from propane-1,3-dithiol and aldehydes) can be de-protonated by strong bases and that the resulting 2-carbanion (28) can be made to react with electrophilic reagents, e.g., alkylated or acylated (Fig. 9.4). 

The reaction of methylenesulphones with allyl halides in the presence of quaternary ammonium salts produces the 1-allyl derivatives [52], unlike the corresponding reaction in the absence of the catalyst in which the SN- product is formed (Scheme 6.5). In contrast, alkylation of resonance stabilized anions derived from allyl sulphones produces complex mixtures [51] (Scheme 6.6). Encumbered allyl sulphones (e.g. 2-methylprop-2-enyl sulphones) tend to give the normal monoalkyl-ated products. Methylene groups, which are activated by two benzenesulphonyl substituents, are readily monoalkylated hydride reduction leads to the dithioacetal and subsequent hydrolysis affords the aldehyde [61]. 

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. 

In the benzoin condensation, one molecule of aldehyde serves as an electrophile. If a carbanion is generated from protected cyanohydrins, a-aminonitriles or dithioacetals, it can react with electrophiles such as alkyl halides, strongly activated aryl halides or alkyl tosylates to form ketones. Amongst other electrophiles which are attacked by the above carbanions are heterocyclic A -oxides, carbonyl compounds, a,p-unsaturated carbonyl compounds, a,3-unsaturated nitriles, acyl halides, Mannich bases, epoxides and chlorotiimethyl derivatives of silicon, germanium and tin. 

Scheme 21). Some important a-sulfinyl carbanions (42) are derived from dithioacetal S-oxides (43), and on subsequent alkylation and hydrolysis they yield the aldehydes (40) (Scheme 22).

Aromatic aldehydes have been reported to undergo 1,1-addition to the ketene dithioacetal S,S-dioxides (46 R = alkyl) in either the presence or absence of benzophenone to give adducts (47). The transformation is initiated by H abstraction from the aromatic aldehyde by the n,K excited state of the sensitizer or substrate aldehyde to form the aroyl radical (48) as intermediate. These adducts may be useful synthetic precursors of inda-nones. 

It is quite interesting that the aromatic aldehyde derived dithioacetal 67 shows different anodic behavior from that of the aliphatic aldehyde derived dithioacetal 70. This can be explained by the pathway shown in Scheme 51. Deprotonation of the cation radical P arising from the aromatic dithioacetal 67 should be more facile than that from P which comes from the alkyl dithioacetal 70 as the former contains more acidic a-hydrogens. 

Synthesis of Dithiocarboxylic Acids and their Derivatives.—The preparation of thioterephthalic acid from l,4-di(chloromethyl)benzene, sulphur, and sodium methoxide (see Vol. 5, p. 179) has beeil reported by another group. In a similar reaction, the addition of chloroacetonitrile to sulphur and triethylamine in DMF, followed by alkylation, gave methyl and ethyl cyanodithioformates. These were not isolated, but they condensed when water was added, giving EfZ mixtures of l,2-di(alkylmercapto)-l,2-dicyanoethylenes. Ethylene dithioacetals from aromatic aldehydes are decomposed by sodium hydride in DMF containing HMPA, with elimination of ethylene and the liberation of an aryIdithiocarboxylate anion this may be alkylated to give the dithioester (Scheme 8). ... 

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