Dithianes dithiane, thioacetal

Dithianes, thioacetals and -ketals, enol thiol ethers. This clay is a useful catalyst for reactions of ketones with thiols. The condensations are usually conducted in refluxing toluene with a Dean-Stark trap for water.1... 

The most utilized Umpolung strategy is based on formyl and acyl anion equivalents derived from 2-lithio-l,3-dithiane species. These are readily generated from 1,3-dithianes (thioacetals) because the hydrogens at C(2) are relatively acidic (p f 31). In this connection it should be noted that thiols (EtSH, pi 11) are stronger acids compared to alcohols (EtOH, 16). Also, the lower ionization potential and the greater polarizability of the valence electrons of sulfur compared to oxygen make the divalent sulfur compounds more nucleophilic in Sj,2 reactions. The polarizability factor may also be responsible for the stabilization of carbanions a to sulfur. ... 

The carbanions derived from thioacetals, however, are typical -synthons. Most frequently used are 1,3-dithianes and C -silylated thioethers (see p. 33f. D. Seebach, 1969, 1973 B.-T. Grobel, 1974,1977). In these derivatives the proton is removed by butyllithium in THF. 

RSSiMe3 [R = Me, Et, (-CH2-)3], Zn, Et20, 0-25°, 70-95% yield. This method is satisfactory for a variety of aldehydes and ketones and is also suitable for the preparation of 1,3-dithianes. Methacrolein gives the product of Michael addition rather than the thioacetal. The less hindered of two ketones is readily protected using this methodology. ... 

GaCl3, CH2CI2, H2O, rt, 20 min."" Thioketals are cleaved in preference to thioacetals and dithianes, which do not react. 

Some cyclic thioacetals have an A-SE2 hydrolysis mechanism,206 as do some 2-aryl-2-methyl-l,3-dithianes, except for the 4-NO2 derivative, which looks more A2-like.207 In 10 vol% dioxane/aqueous HC104 mixtures, reactive 2-aryl-2-phenyl-l,3-dithianes are believed to have an A-SE2 hydrolysis mechanism, whereas the least reactive ones have an A2 mechanism.130 Isothiocyanates are believed to hydrolyze by a mechanism that involves simultaneous proton transfer to nitrogen and attack of water at carbon in a cyclic transition... 

Thioacetals and thioketals have significant synthetic potential for use in organic chemistry but are often neglected because of their unpleasant odor. A polymeric reagent for the preparation of ketones via 1,3-dithianes has been reported using... 

Dithianes These are thioacetals which can be prepared by treating an aldehyde with 1,3-propanedithiol in the presence of trace of acid. 

Ketene thioacetals can also be used as ketene equivalents in the preparation of cyclobutanones and cyclobutanes. Boron trifluoride catalyzes the [2 + 2] cycloaddition of 2-[(l-pyrro-lidinyl)mcthylene]-1,3-dithiane (39) with dimethyl maleate (40).17 Although the cycloadduct is obtained in good yield, stereochemical integrity is not maintained and the thermodynamically most stable isomer predominates. 

Carbon-13 shift values of parent heterocycloalkanes [408] collected in Table 4.61 are essentally determined by the heteroatom electronegativity, in analogy to the behavior of open-chain ethers, acetals, thioethers, thioacetals, secondary and tertiary amines. Similarly to cyclopropanes, three-membered heterocycloalkanes (oxirane, thiirane, and azirane derivatives) display outstandingly small carbon-13 shift values due to their particular bonding state. Empirical increment systems based on eq. (4.1) permit shift predictions of alkyl- and phenyl-substituted oxiranes [409] and of methyl-substituted tetrahydropyrans, tetrahydrothiapyrans, piperidines, 1,3-dithianes, and 1,3-oxathianes [408], respectively. Methyl increments of these heterocycloalkanes are closely related to those derived for cyclohexane (Table 4.7) due to common structural features of six-membered rings. 

Chiral /J-amino acyl silanes have been prepared through the addition of 2-lithio-2-trimethylsilyl-l,3-dithiane to enantiomerically pure A-tosylaziridines followed by mercury-mediated thioacetal hydrolysis113. 

Cyanide (one carbon) and acetylene (two carbons) are limited and other acyl anion equivalents are more versatile. Dithians are thioacetals of aldehydes that can be deprotonated between the two sulfur atoms by strong bases such as BuLi. Reaction with a second aldehyde gives 27 and hydrolysis of the thioacetal by acid, usually catalysed by Cu(II) or Hg(II), gives the a-hydroxyketone 4. The disconnection is that shown on diagram 4 and the lithium derivative 26 acts as the acyl anion 2. Unlike previous methods, R1 does not have to be H or Me. 

Five steps were required to convert 75 into the iodide coupling partner 44 needed for union with dithiane 43 (Scheme 17.16). Thioacetal formation31 and concomitant deketalisation were instigated by reacting 75 with 1,3-propanedithiol under Lewis acid conditions. Triol 76 was isolated in 65% yield. The less-hindered primary hydroxyl of 76 was then selectively 0-tosylated, and the remaining hydroxyls masked as tert-butyldimethyl silyl (TBDMS) ethers. Iodide displacement on 77 with sodium iodide and copper bronze,32 and transketalisation with N-chlorosuccinimide (NCS)/silver nitrate33 finally secured 44. 

The dithiane anion is a good nucleophile in SN2 reactions. After it has been alkylated, the thioacetal group can be removed by hydrolysis using Hg2+ as a Lewis acid catalyst. 

In general, thioacetals can be made in a similar way to normal (oxygen-based) acetals-by treatment of an aldehyde or a ketone with a thiol and an acid catalyst—though a Lewis acid such as BF3 is usually needed rather than a pro tic acid. The most easily made, most stable toward hydrolysis, and most reactive towards alkylation are cyclic thioacetals derived from 1,3-propanedithiol, known as dithianes. 

Dithianes are extremely important compounds in organic synthesis because going from ketone to thioacetal inverts the polarity at the functionalized carbon atom. Aldehydes, as you are well aware, are electrophiles at the C=0 carbon atom, but dithioacetals, through deprotonation to an anion, are nucleophilic at this same atom. 

After the dithianes have been alkylated, they can be hydrolysed to give back the carbonyl groups. Alternatively, hydrogenation using feaney nickel replaces the thioacetal with a CH2 group and gives the unsubstituted cyclophane. 

As with our other acyl dithiane oxide systems, the thioacetal moiety can be readily removed by hydrolysis, in this case without affecting the dihydroisoxazoline ring (Scheme 11). 

Several cyclic thioacetals 266-268, closely related to 1,3-dithiane, have been described as formyl anion equivalents. 1,3,5-Trithiane (266)442,443, as well as 4,5-dihydro-5-methyl-... 

Cleavage of thioacetals. Fe(NO,)j or CulNO,) supported on the clay cleaves thioacetals to the carboniyl compound in essentially quantitative yield. They are particularly efficient for cleavage of dithianes and dithiolancs. 

Ketene thioacetals. The enolate (1) of 2-carbomethoxy-1,3-dithiane does not normally react with aldehydes or ketones, but a 1 1 mixture of trimethylacetyl chloride and an aldehyde reacts in THF to form the pivaloxy ester 2. This product undergoes dccar-boalkoxylation (9, 283 11, 301) when heated in ilry DMF with excess Li I to form ketene thioacetals (3). 

Open chain and cyclic thioacetals 1,3-Dithiolane and 1,3-dithiane derivatives are versatile intermediates in the synthesis and interconversion of monocarbonyl and 1,2-dicarbonyl compounds. Protection of carbonyl groups as their open-chain and cyclic thioacetals is an important method in the synthesis of organic molecules. Thioacetals are stable... 

Some of the problems associated with the synthesis of a-dicarbonyl starting materials have been alleviated by the use of propane-1,3-dithiol, which reacts with aldehydes to give cyclic thioacetals. With butyllithium the resulting stable dithiane anions (134) can be transformed into a-diketones or a-hydroxy ketones (Scheme 73). A further approach to such compounds is found in the reaction of a-ketonitrate esters with sodium acetate (Scheme 73), while aryl a-diketones are also available from a-ketoanils (prepared from the cyanide-ion-catalyzed transformation of aromatic aldimines) (70AHC(12)103). 

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