Dithianes from dithiols

The preparation of dithianes from enamines by reaction with trimethylene dithiotosylate (propane-1,3-dithiol di-p-toluenesulfonate) has been applied with enamines derived from oholostan 3 one, aceto-acetic ester, and phenylacetone.6 7 Reactions of trimethylene dithiotosylate with hydroxymethylene derivatives of ketones also give rise to dithianes thus the hydroxymethylene derivative of cholest-4-en-3-one can be converted to 2,2-(trimethylenedithio)cholest-4-en-3-one. 1,3-Dithiolanes are obtained in a similar manner by reaction of ethylene dithiotosylate1 with the appropriately activated substrate.5,7... 

The oxidation products of dithiols are insoluble and removed with the clay residues by the filtration step, and the method appears particularly suitable for dithioacetals derived from dithiols as dithianes for instance. For other dithioacetals a further purification step was necessary. 

The procedure for the preparation of a dithiolane from a hydroxy-methylene derivative of a ketone and ethylene dithiotosylate (ethane-1,2-dithiol di-p-toluenesulfonate) can be varied to produce dithianes when the latter reagent is replaced by trimethylene dithiotosylate.8,4 The dithiotosylates also react with enamine derivatives to produce dithiaspiro compounds.4,5... 

Dithioketals, especially the cyclic dithiolanes and dithianes, are also useful carbonyl-protecting groups. These can be formed from the corresponding dithiols by Lewis acid-catalyzed reactions. The catalysts that are used include BF3, Mg(03SCF3)2, Zn(03SCF3)2, and LaCl3.100 S-Trimethylsilyl ethers of thiols and dithiols also react with ketones to form dithioketals.101... 

R,56)-Dihydroxy-l,2-dithiane was synthesized from (2R,36)-dihydroxybutane-l,4-dithiol in 40% yield <1989SUL251>. 

The stoichiometric equivalents of halofluorides have been recently applied to transform alkylene dithioacetals into gcm-difluorides.70-71 Dithioacetals such as 1,3-dithiolanes and 1,3-dithianes arc readily obtained from the corresponding carbonyl compounds by the reaction with ethane-1,2-dithiol or propane-1,3-dithiol in the presence of the complexes boron trifluoride-bis(acetic acid) or boron trifluoride-diethyl ether. Using a two-step procedure, a range of aldehydes and ketones can be converted into gem-difluorides under mild conditions. 

In particular, 1,3-dithiane prepared from dimethoxymethane (methylal) and pro pane-1,3-dithiol in the presence of boron trifluoride-etherate,237 and 2-alkyl-1,3-dithianes prepared similarly from aldehydes,2383 are important acyl anion equivalents. These and other uses are discussed in Sections 5.7.5, p. 596, and 6.6.1, p. 909. A wide-ranging review of the reversal of polarity of the carbonyl group through the formation of these sulphur-containing reagents has emphasised their value in organic synthesis.2388... 

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). 

Although 1,2-dicarbonyl substrates (especially unsymmetrical benzils) are often difficult to make, there are a number of approaches which may be appropriate. Propane-1,3-dithiol reacts with aldehydes to give cyclic thioacetals (in 52-91% yields) which form stable dithiane anions when treated with butyllithium. Subsequent quenching with an acid chloride followed by mercury(ll) chloride treatment gives a 1,2-dicarbonyl species. Alternatively, substitution of an aldehyde for the acid chloride gives rise eventually to an a-hydroxycarbonyl derivative (Scheme 5.1.2) [16j. An alternative approach to a-ketoaldehydes (82-86% yields) reacts an a-ketonitrate ester with sodium acetate in DMSO [17]. Aryl a-diketones can be made from a-ketoanils, which are in turn made by cyanide ion-catalysed transformation of aromatic aldimines [18], and the range of unsymmetrical benzils has been increased by... 

As seen in 10-6, departure of the leaving group from an acetal gives a particularly stable carbocation. It is also possible to convert a dimethylketal directly to a dithiane by reaction with butane 1,4-dithiol on clay. ° These are equilibrium reactions, and most often the equilibrium is shifted by removing the lower-boiling alcohol by distillation. Enol ethers can be prepared by treating an alcohol with an enol ester or a different enol ether, with mercuric acetate as a catalyst, example. 

Dithians 20 illustrate this approach and have been remarkably popular considering the problems in their use. They can be made from aldehydes with propane-1,3-dithiol and Lewis acid catalysis. They are deprotonated with BuLi and react with alkyl halides, epoxides, and carbonyl compounds (E+) to give 22 and hence 19 after hydrolysis. The hydrolysis is by no means easy there are many methods and this alone should warn us that none is very good.6... 

In a complementary process, the reaction of active methylene compounds, and derivatives such as the enamine shown, with ditosylated 1,3-dithiols, derived from the reaction of 1,3-dibromo-propane with potassium thiotosylate, can provide unusually substituted 1,3-dithianes (Equation... 

Dithians such as (261) are synthesized from 3-(trimethylsilyl)propynal and propylene-1,3-dithiol, and are versatile intermediates. ... 

Dithiobenzoates PhCS2R (R = allyl, propargyl, or benzyl) add to dimethyl acetylenedicarboxylate to form the dithioles (288) with migration of the group R. Piperidine catalyses the addition of acetylenic ketones Ar COC=CAr to 4-methylbenzene-l,2-dithiol to give the benzodithioles (289). The reaction of the acetal BrCH2CH(OEt)2 with ethanedithiol yields a mixture of the bis(dithiolan) (291) and derivatives of dithian, which are formed, respectively, from the cations (290) and (292). ... 

Dithians and 1,4-Dithians.—Equimolar amounts of propane-1,3-dithiol and phosgene condensed to give a high yield of l,3-dithian-2-one by a procedure which is a considerable improvement on earlier methods.A 1,3-dithian is also obtained when an aldehyde is condensed with a 1,3-dimercaptoacetone (Scheme 10) 300 mechanism of the formation of 2,3-dihydro-1,4-dithians (323) from a-halogeno-acetals (Scheme 11) appears to involve the carbonium ion (322). ... 

Kitazume et al. have also investigated the use of [EtDBU][OTf as a medium for the formation of heterocydic compounds [242], Compounds such as 2-hydroxymethylaniline readily condense with benzaldehyde to give the corresponding benzoxazine (Scheme 5.2-105). The product of the reaction is readily extracted vyith solvents such as diethyl ether and the ionic liquid can be recycled and reused. Thioacetals and dithianes formed from the condensation of 2-mercaptoethanol and ethane-l,2-dithiol with aldehydes also form readily in... 

It is possible to abstract a proton from a 2-alkylated-1,3-dithiane and perform a second alkylation reaction. If the 2-alkylated-1,3-dithiane is prepared from the aldehyde with propane-1,3-dithiol, then after alkylation and hydrolysis the sequence provides a method for converting an aldehyde into a ketone. Starting with the commercially available 1,3-dithiane, an alkyl halide or sulfonate can be converted into the homologous aldehyde. Two alkyl groups can actually be introduced successively without isolation of the intermediates and this has been applied to the synthesis of three- to seven-membered cyclic ketones. 

The synthesis of 2,2-dimethyl-3-methylene-l,4-dithiepane (196) was achieved either by treatment of a-hydroxy-l,3-dithiane (195 R = H) with POCI3 in pyridine, or by thermolysis of the corresponding acetate (195 R = Ac) <85J0C4218>. 6-Methylene-1,4-dithiepane (198) could be obtained from 2-methylene-1,3-dithiol and dibromoethane <73GEPiooooi>, and the synthesis of derivative (199) has also been reported <7iiJC904>. 

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