Dithioacetals formation

Emil Fischer s initial studies [1] focused on dithioacetal formation from a variety of simple aldopentoses, aldohexoses, and aldoheptoses. The products were obtained by simply treating the sugar with an excess of ethanethiol in concentrated hydrochloric acid at low temperature ( 0°C). Many of these dithioacetals have low water solubility, crystallize spontaneously from the reaction mixtures, and can be isolated by simple filtration and washing with odd water. Fischer s key paper [1] also outlined most of the major reaction modes of the diethyl dithioacetal derivatives, later developed in detail, and thus paved the way for subsequent studies into this important class of sugar derivative. 

Reactions of the carbonyl group of inososes include the addition of diazoalkanes, dithioacetal formation, reduction, hydrogenolysis, and phenyl-hydrazone formation. The epoxide CXXX, which is formed from scyllo-inosose pentaacetate and diazomethane, is the starting material for a considerable series of seven-carbon derivatives.1 Some of the newer compounds of this group are discussed on pages 187 and 188. 

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. 

Methods of chain extensions generally use linear sugars with free aldehydes mostly prepared via dithioacetal formation, protection of the remaining hydroxyl groups and aldehyde recovery. This allows one to use all methods applicable to aldehydes. Among others, the condensation of ethyl diazoacetate has been studied in detail by L6pez-Herrera [207] in a new synthesis of KDO by a two carbon homologation of an open-chain mannose derivative. 

Ketene Dithioacetal Formation and Thia-Claisen Rearrangement General Procedure624 ... 

It would seem that, under mercaptalation conditions, dithioacetal formation is a fast, kinetically controlled reaction, followed by a slower reaction which, at equilibrium, gives a distribution of products, including free aldose, thioglycosides, and dithioacetal, according to their thermodynamic stabilities in the system. 

Epoxidation of the olefin occurs with high diastereofacial selectivity to give carbamoyl-oxirane 945. This epoxide is not extremely stable, and is treated directly with methanesulfonic acid to afford the j5-D- a/o-furanoside 946. The stereocenter at C-2 must be inverted to match the configuration of the natural product. This is accomplished by triflate formation followed by an Sn2 reaction with cesium acetate. Hydrolysis of the OAc group furnishes the desired P D-ga/ac o-furanoside (947). 0-Methylation, benzyl group hydrogenolysis, acidic hydrolysis, and dithioacetal formation completes the synthesis of 948 in 11 steps and 5.7% overall yield from 929 [252]. 

Numerous other examples of dithioacetal formation, including selective formations, have been well documented, but the above suggest the scope. 

The pentoses may be converted by the conventional sequence (5) of dithioacetal formation, acetylation, and demercaptalation into the respective aldehydo-oentose 2,3,4,5-tetraacetates, which afford by Wittig chain-extension (2) the desired dienophiles. Thus aldehydo-D-arabinose 2,3,4,5-tetraacetate reacted with Ph3PCHC02Me in boiling benzene to give 90% of the pure, crystalline E-unsaturated sugar derivative 6, and the corresponding enantiomer was likewise prepared from L-arabinose. 

Dithioacetal Formation. Dithioacetals are prepared from activated methylene compounds with MeSS02Me absorbed on potassium fluoride-alumina (eq 7). Microwave irradiation without solvent provides a powerful activation for this preparation. MeSCl gives only poor yields and MeSSMe does not react under these conditions. ... 

Literature reveals that in the oxidative cyclization of aldeltyde and o-phenylene-diamine, the formation of the required 2-aiyl-l/f-benzimidazole is accompanied by the occurrence of 1-benzylated 2-aryl-1/f-benzimidazoles as side products [46], and sometimes these disubstituted derivatives have been isolated as the main product [47, 48]. The present protocol gives 2-aryl-1/7-benzimidazole selectively. Further, we extended our studies on oxidative reactions of aldehydes with o-aminothiophe-nol. Although thiols are good nucleophiles and SET agents [49], in present studies, no substitution of the halogen atom or the nitro group, dealkylation/debenzoy lation, took place as reported earlier [50-52]. Fmiher, the dithioacetal formation is a common reaction of aldehydes with thiols [53] no competitive dithioacetal formation was observed imder the present conditions. Doping of Mn promotes the activity and... 

Ketene Dithioacetal Formation. These versatile intermediates arise from 1,3-dithiane anions by elimination (eq 8) or vinylogous alkylation (eq 4), and by condensation of carboxylic acid derivatives with (1) (eq 13). Ketene dithioacetals derived from lactones can cyclize to give dithio orthoesters, which can be selectively deprotected (eq 16). ... 

The DBSA-system is also applicable for the dithioacetalization of aldehdyes and ketones with 1,2-ethanedithiol to give the corresponding dithioacetals (Scheme 5.4, d). Increasing the reaction temperature decreases the yield of the products. Interestingly, increases in the concentration of the surfactant also decrease the yield of products formed, while shortening the alkyl chain of the surfactant abolishes its catalytic activity. Optical microscopy shows the formation of micelles, which are proposed to form hydrophobic environments and decrease the effective concentration of water and facilitate the dehydrative condensation reactions. 

The differing nucleophilicity of acetate and trifluoroacetate anion determined the manner in which naphtho[l,8-/yt]-l,5-dithiocinc sulfoxide 127 rearranged on treatment with acetic and trifluoroacetic anhydrides. In both cases, the reaction proceeded through formation of a disulfonium dication 128, but the final products were different. When acetic anhydride was used, the reaction afforded the corresponding a-acetylsulfide 130, a normal product of the Pummerer rearrangement, while trifluoroacetic anhydride caused isomerization with formation of dithioacetal 132 (see Scheme 16) <1995HAC559>. 

Another route involves a palladium-copper-catalyzed tandem carbon-carbon formation/cycloaddition sequence (Equation 12) <2005TL8531>. Notably, cycloadditions of azide to the internal alkynes failed under click chemistry reaction conditions <2003DDT1128>. Cyclization under oxidative conditions has been reported from dithioacetal 163 (Equation 13) <1996TL3925>. The formation of 164 as a single diastereoisomer has been explained by stereoelectronic effects. 

An elegant method for the formation of glycosidic bonds from acyclic dithioacetal monosulfoxides and glycosyl acceptors with triflic anhydride has been developed. This method takes advantage of the sulfenyl triflate generated from the reaction of... 

Extended irradiation of the diethyl dithioacetal 44 increases the yield of L-fucitol (46) at the expense of 1-S-ethyl-l-thio-D-galactitol (45) also galactitol (52) was isolated from the photolysis mixture.109 The intermediacy of 45 in the formation of 46, a possibility that was suggested by the extended photolysis of 44, is supported by the observation that irradiation of 45 in methanol produces L-fucitol (46) in 44% yield.109 (Compounds 47 and 52 also are formed during irradiation of 45, but in low yield.) The mechanism for sulfide photoreaction parallels that109 for the alkyl dithioacetals (see Scheme 18). 

The formation of 2,3,4-tri-0-acetyl-5-5-ethyl-5-thio-L-arabinose diethyl dithioacetal (67) when a-L-arabinopyranose tetraacetate (57) was treated o) th ethanethiol in the presence of either zinc chloride or boron trichloride was rationalised by the sequence of reactions shown subsequent work (see below) suggests that an orthoester may be inter-... 

Dithioacetals derived from heteropine 177 smoothly react with methylene iodide in the presence of a zinc-copper couple in refluxing ether to give the corresponding fused thiophenes 178. The suggested mechanism involves formation of an ylide which undergoes intramolecular aldol-type condensation assisted by coordination of zinc with a carbonyl followed by demethylation of the S-methylthiophenium species (Scheme 35 (1989TL3093)). 

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