Dithioacetals, alkylation

Much higher asymmetric induction was observed in the two-phase oxidation of simple alkyl aryl and diaryl sulphides296, substituted alkyl aryl sulphides297 and dithioacetals of formaldehyde298 by sodium metaperiodate in the presence of proteins such as bovine serum y-globulin and egg albumin. Optical purities of the sulphoxides so formed ranged between 20 and 85%. 

The anions of alkyl alkylthiomethyl sulphoxides have found a much broader application. Methyl methylthiomethyl sulphoxide 324 was first introduced by Ogura and Tsuchihashi in 1971412 and ethyl ethylthiomethyl sulphoxide 325 was synthesized by Schlessinger and coworkers in 1973413. Ogura and Tsuchihashi performed alkylation of 324 and obtained a series of substituted dithioacetal monoxides 326 which were then hydrolysed to the corresponding aldehydes (equation 181 Table 17)412. 

Entries 3 to 5 show the use of alternative sources of the one carbon unit. In Entry 3, a tertiary alcohol is formed with one of the alkyl groups being derived from the dithioacetal reagent. Related procedures have been developed for ketones and tertiary alcohols using 2-lithio-2-alkyl-l,3-benzothiole as the source of the linking carbon.14 Problem 9.3 deals with the mechanisms of these reactions. 

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. 

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). 

Ketene dithioacetals are obtained in very good yield (>95%) from the disodium salt of 2-cyanoethene-l,l-dithiolate with a range of alkylating agents in the presence of tetra-n-butylammonium bromide [26]. 

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]. 

Double-tail derivatives were sometimes prepared by short syntheses thus, dithioacetals 9 were obtained by condensation of a free carbohydrate with the corresponding -alkanethiol [50] whereas the 6,6-di-O-alkyl derivatives 29 were synthesized by the reaction of alkyl magnesium bromide with l,2 3,4-di-0-iso-propylidene-D-galacturonic acid [62]. 

From the synthetic point of view, the most important a-sulfinyl carbanions appear to be those derived from dithioacetal S-oxides which are a synthon for acyl anions65. However, the yields of the alkylation reaction were found to be low. In spite of the fact that dithiane S-oxides have been intensively studied66 63, their synthetic applications are limited,... 

Cyanogen Iodide (ICN) has been used extensively for the cyanation of alkenes and aromatic compounds [12], iodination of aromatic compounds [13], formation of disulfide bonds in peptides [14], conversion of dithioacetals to cyanothioacetals [15], formation of trans-olefins from dialkylvinylboranes [16], lactonization of alkene esters [17], formation of guanidines [18], lactamization [19], formation of a-thioethter nitriles [20], iodocyanation of alkenes [21], conversion of alkynes to alkyl-iodo alkenes [22], cyanation/iodination of P-diketones [23], and formation of alkynyl iodides [24]. The products obtained from the reaction of ICN with MFA in refluxing chloroform were rrans-16-iodo-17-cyanomarcfortine A (14)... 

The second route involves the palladium catalyzed coupling of iodoaniline 51 with the acyl silane 54 in the presence of DABCO to give the 2-trimethylsilyl indole 55. The acyl silane 54 was prepared by alkylation of 1,3-dithianyl-trimethylsilane with (3-bromopropyl)-dimethylamine to give 56, followed by removal of the dithioacetal with mercuric oxide and mercuric chloride. Finally, desilylation of 55 in aqueous HCl and methanol afforded rizatriptan (4). 

Ethylene dithioacetals of benzophenone and its 4-fluoro-, 4-bromo-, 4,4 -difluoro-, 4,4 -dichlo-ro-, and 3,5-dimethyl-substituted analogs react with sulfuryl chloride or sttlfuryl chloride fluoride in hydrogen fluoride/ pyridine at — 78 C to room temperature to give the corresponding geminal difluorides in 85-90% yield. The reaction is, however, not applicable to dialkyl or alkyl aryl ketones as they undergo chlorination under these conditions.73... 

Under the same conditions a low yield of dithioacetal was isolated for R1 = t-Bu (23% with R3 = Et). Only dimerization products of carbene intermediates were obtained for R1 = phenyl however, the corresponding unstable magnesiodithioacetal could be trapped by addition of a good alkylating species before that of the Grignard reagent. An 80% yield of dithioacetal (R1 = Ph, R3 = Et or i-Pr, E = Me) was thus isolated. 

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... 

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