Formaldehyde dithioacetals

Treatment of the optically active formaldehyde dithioacetal monoxide with ethyl benzoate in the presence of sodium hydride gives the benzoylated product as a diastereomeric mixture in a thermodynamically controlled (65 35) ratio66. 

Asymmetric oxidation of formaldehyde dithioacetals with aqueous NaI04 was realized by Ogura et al. in the presence of a catalytic amount of BSA (0.005-0.02 mol equiv.) [96]. Under conditions the authors used, the starting sulfide was virtually insoluble in water (pH 9.2), and the best results were obtained at low concentrations of BSA. This result clearly indicates that the BSA/sulfide ratio is not the controlling factor of enantioselectivity. With this protocol, p-Tol-S-CH2-S-p-Tol could be transformed into monosulfoxide with 60% ee. The same protocol gave isopropyl phenyl sulfoxide with 60% ee. 

Corynebacterium equi IF0 3730 gave high enantioselectivity in the oxidation of aryl alkyl sulfides [106], The results listed in Scheme 6C, 11 arise from experiments with no formation of sulfone, which occurs quite easily in several cases. Thio ketals and thio acetals were oxidized into mono S-oxides by various fungal species with enantioselectivity up to 70% ee [107]. Corynebacterium equi was very successfully used in the oxidation of formaldehyde dithioacetals to mono S-oxide or sulfone-sulfoxide, depending on the substrates. Thus n-Bu-S-CH-S-n-Bu was transformed to n-Bu-S02-CH2-S(0)-n-Bu with more than 95% ee in 70% yield. 

Formaldehyde dithioacetals are often utilized as synthetic equivalents of formyl anion ( CHO) and carbonyl dianion ( "C=0). 1,3-Dithiane is commonly used its 2-H is quite acidic (pKt = 31.1) due to sta-... 

The synthesis of formaldehyde dithioacetals may be achieved through a reaction with thiols and dichloromethane in the presence of Wilkinson s catalyst and triethylamine (eq 83). The reaction is simple and takes place under very mUd reaction conditions. 

Oxidation of sulfides in the presence of bovine serum albumin (BSA) gave sulfoxides with quite high ee s (up to 90%) [92-94]. Moreover, the reaction could be carried out catalytically with respect to BSA. Ogura et al. used NalO BSA in a two-phase system for the oxidation of formaldehyde dithioacetals [95], while Colonna et al took BSA (5% mol equiv) in buffer solution for oxidation of various sulfides [96-99]. 

Ogura K, Fujita M, lida H (1980) A two-phase reaction catalyzed by a protein. Asymmetric oxidation of formaldehyde dithioacetals with aqueous sodium metaperiodate. Tetrahedron Lett 21 2233-2236 Ohnishi Y, Kagami M, Ohno A (1975a) Reduction by a model of NAD(P)H. Effect of metal ion and stereochemistry on the reduction of a-keto esters by 1,4-dihydronicotinamide derivatives. J Am Chem Soc 97 4766-4768... 

Much higher asymmetric induction was observed in the two-phase oxidation of simple alkyl aryl and diaryl sulphides , substituted alkyl aryl sulphides and dithioacetals of formaldehyde 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%. 

Ogura [296, 297] has proposed other interesting uses of MMTS (also known as FAMSO, for formaldehyde dimethyl dithioacetal S-oxide) and also of the two following dithioacetal monosulfones ... 

KETONES N.O-Dimethylhydroxylamine hydrochloride. N,N,-Diphenyl-/>-mcthoxyphenylchloromethyleniminum chloride. Formaldehyde dimethyl dithioacetal S.S-dioxidc 4-Fonmyl l methylpyridiniuni bcnzencsullonatc. l.ithi[Pg.651]

METHYL CARBOXYLATES Formaldehyde dimethyl dithioacetal S,S-dioxide. 

The protection of formaldehyde or other aldehydes as acyclic dithioacetals, sulfanylethers, sulfonylethers, thiosulfoxides, diselenoacetals, aminothioacetals and aminals, as well as cyclic dithioacetals, dioxolanes, oxazolidines and imidazolidines, allows the preparation of different type of protected acyllithium derivatives IV-XI by deprotonation (see... 

Dithioacetals of aldehydes are sources of carbanions and hence may be used to form new C-C bonds in reactions in which the formerly electron-deficient character of the aldehydic carbon has been reversed. The 1,3-dithianes derived from formaldehyde or a higher aldehyde may be metallated and then alkylated (Scheme 2.27). Hydrolysis of the dithioac-etal is usually carried out in the presence of a thiophilic (sulfur seeking) metal salt such as a mercury salt. The insoluble sulfides cause the equilibrium to move in favour of the parent carbonyl compound. 

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],... 

Formaldehyde dimethyl dithioacetal 5-oxide (FAMSO 113) and its ethyl analog are widely used as synthetic carbonyl equivalents. - Addition of the lithio derivative of (113) to aldehydes and ketones followed by acidic hydrolysis is a preparative method for a-hydroxy aldehyde derivatives (equation 27). A chiral analog of (113), (5)-formaldehyde di-p-tolyl dithioacetal 5-oxide (114), can be synthesized from (-)-mentyl (/ )-p-toluenesulfinate. °° The reaction of the lithio derivative of (5)-(114)... 

The anion of an aldehyde dithioacetal 5-oxide is well known to add to a,3-unsaturated carbonyl compounds. " Conjugate addition of formaldehyde di-p-tolyl dithioacetal 5-oxide (114) to open-chain and cyclic enones is achieved by using HMPA as a polar cosolvent in THF (-78 C)." The lithio derivative of (5)-(114) was found to add to 2-cyclopentenone with asymmetric induction. Transformation of the dithioacetal part into a formyl group gives 3-formylcyclopentanone in 39% enantiomeric excess (equation 28)." Interestingly, highly asymmetric induction is observed in the conjugate addition of the... 

---