Aldehydes reactions with dithioacetals

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. 

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. 

Chiral a-methoxy aldehydes.2 The anion of 1 undergoes 1,2-addition to bcnzaldehyde in quantitative yield. The adduct can be methylated under phase-transfer conditions and then reduced3 to give the dithioacetal 2, from which the aldehyde 3 is liberated by reaction with I2 and NaIlC03.4 The optical yield of 3 is >70%. 

The second method consists in the reaction of 3-mercaptopropionic acid amides with various aldehydes and ketones (method B) this reaction proceeds via the formation of thiohemiacetal 143. Method B was modifed (in the case of p-chlorobenzaldehyde) by means of dithioacetal 144, which was isolated and then introduced into the reaction with the second mole of aldehyde (Scheme 49). 

Optically active dithioacetals can be prepared by use of the thiolacid prepared from (R)-( - )-a-methoxyphenylacetic acid by reaction with oxalyl chloride and then with NaSH. This thiolacid reacts with an aldehyde and a thiol to form the mixed thioacetals corresponding to 1 as a 1 1 mixture of diastereomers, separable by chromatography (—75% yield). These are convertible into optically active dithioacetals corresponding to 2 with no loss of diastereomeric purity. 

Aldehydes may be prepared from the lower homolog or a ketone or ester by reaction with the anion of formaldehyde mono- or dithioacetal. The j6-hydroxythioacetal may be reduced with elimination of a hydroxyl group and phenylthiolate. The resulting enol ether or thioenol ether can be transformed into an aldehyde on acid hydrolysis or reaction with mercuric chloride [82],... 

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. ... 

In order to confirm the structures of solanapyrones, chemical synthesis of these phytotoxins were attempted based on biogenetic consideration [55], The retro synthesis envisaged intramolecular Diels-Alder reaction of the achiral polyketide triene (a), a key intermediate, which is further divided into a pyrone moiety (b) and a diene moiety (c). The moieties a and b were prepared from dehydroacetic acid and hexadienyl acetate, respectively. Aldol condensation of the aldehyde (72) with the dithioacetal (73) gave a dienol, which was further converted to a triene (74). The intramolecular Diels-Alder reaction of 74 in toluene at 170-190 °C for 1 hr in a sealed tube yielded a mixture of the adducts (75) and (76) in a ratio of 1 2. This product ratio depends on the solvents, i.e. in water (1 7), and should be useful in differentiating between artificial and enzymatic reactions in biosynthetic studies. Removal of the thioacetal groups in 75 and 76 yielded solanapyrone A (67) and D (70) in a ratio of 3 5. Though solanapyrone D (70) had not been isolated from the natural resources at this stage, the structure and stereochemistry were confirmed by H NMR spectrum. 

A substantial body of literature has been devoted to the study of condensation reactions of dithioacetals with aldehydes and ketones. Although phosphoric anhydride has been used as a catalyst for these... 

Looking carefully at the current literature we have learned that the ketene dithioacetal chemistry, widely used for one-carbon homologation of carbonyl compounds, has never been utilized for the construction of ulosonic acids [129]. Besides, ketene dithioacetals, readily available from ketones and aldehydes via the reaction with the ylides generated from substituted dithioacetals in the Peterson, Wittig or Homer-Emmons olefmation, have never been synthesized from lactones. 

Thioacetalization. In the reaction with 1,2-ethanedithiol, aldehydes and ketones are converted to dithioacetals very rapidly at room temperature (17 examples, 75-99% yield),... 

Ketene dithioacetals. This reagent (1) can be used for preparation of ketene dithioacctals by reaction with triphcnylphosphine or triethyl phosphite to form 2 or 5. I hc former reagent (2) can be used to form ketene dithioacctals (4) from aldehvalcs the hitler reagent (5) can be used with cither aldehydes or ketones. 

Dithioacetals, 1,3-dithianes or 13-dithiolanes are prepared by reaction of the corresponding carbonyl compound in the presence of an acid catalyst (cone. HQ, Lewis acids such as Znh, BFs EtaO, TMS-Cl, etc.) with a thiol or dithiol. Silica gel treated with thionyl chloride was found to be an effective as well as selective catalyst for thioacetalization of aldehydes. Thioacetalization can also be achieved using a (polystyryl)diphenylphosphine-4odine complex as a catalyst Conversion of aldehydes or acetals into 1,3-dithianes is achieved with the aid of organotin thioalkoxides and organotin triflates or with 2,2-di-methyl-2-sila-l,3-dithiane. Direct conversion of carboxylic acids to 1,3-dithianes can be carried out by reaction with 1,3,2-dithiabomenane-dimethyl sulfide and tin(II) chloride or 1,3,2-dithiaborolene with trichloromethyllithium followed by basic hydrolysis. 

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