Oxidation of dithioacetals

Direct anodic oxidation of iodobenzene and /Mira-methyliodoben-zene did not give the corresponding hypervalent difluorides. Therefore, indirect anodic oxidation was attempted using a chloride ion mediator. In this case, the desired difluoro products are not formed but instead a novel hypervalent iodobenzene derivative, such as 73, having I-F and I-Cl bonds is produced. It was found that difluorina-tion occurs by the reaction of dithioacetals with iodobenzene chlo-rofluorides. Indirect anodic oxidation of dithioacetals by using a catalytic amount of para-methoxyiodobenzene was attempted as shown in Scheme 55 and it was found that desulfurizative difluorina-... 

Chiba K, Uchiyama T, Kim S, Kitano Y, Tada M (2001) Benzylic inteimolecular carbon-carbon bond formation by selective anodic oxidation of dithioacetals. Org Lett 3 1245-1248... 

Synthesis of a-alkylthioalkyl sulphones by oxidation of dithioacetals with KMn04 has been reported." ... 

Scheme 19.42 Asymmetric oxidations of dithioacetals catalysed by Al(salalen).

Anodic oxidation of dithioacetals gives the disulphide, rather than the expected sulphoxide, sulphone, or sulphonium salt (Scheme 5). Further oxidation to the thiolsulphonate can be brought about by prolonged electrolysis. Di-t-butyl peroxide initiates a homolytic 1,2-shift so as to put another carbon atom between the alkylthio-groups in a dithioacetal, resulting in a l,3-bis(alkylthio)alkane... 

Enantioselective oxidation of cyclic dithioacetals to monosulfoxides catalyzed by bacterial cyclohexanone monooxygenases 96CC2303. 

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%. 

Oxidation of cyclic phosphonoformaldehyde dithioacetal, using the Modena protocol, yields the trans disulfoxide 121 in excellent enantiomeric excess. Then 121, via HWE olefination and oxidation of the double bond has been used for the diastereoselective preparation of spirocyclic his-sulfinyl oxiranes (new versatile intermediates in asymmetric synthesis) [79] (Scheme 37). 

Triazoline imino sugar derivatives 297 that are prospective glycosidase inhibitors have been prepared as single diastereomers in high yield via an lAOC reaction of in situ generated azido alkene 296 (Eq. 32) [78]. m-CPBA oxidation of the dithioacetal groups in the 0-acetylated 5-azido-5-deoxydibenzyl dithio-acetal of o-xylose or D-ribose 294 to the bis-sulfone 295, followed by loss of HOAc between C-1 and C-2 provided the lAOC precursor 296. 

The differing nucleophilicity of acetate and trifluoroacetate anion determines the direction in which naphtho[l,8-b,c]-l,5-dithiocine-l-oxide 59 rearranges on treatment with acetic and trifluoroacetic anhydrides. In both cases the reaction proceeds through formation of a disulfonium dication, but the final products are different. When acetic anhydride is used, the reaction affords the corresponding a-acetylsulfide 60 - a normal product of the Pummerer rearrangement, while trifluoroacetic anhydride causes isomerization with formation of dithioacetal 61 (Scheme 22).87... 

D-Galactose was converted by ethanethiol and hydrochloric acid into crystalline D-galactose diethyl dithioacetal, which was acetonated with acetone-zinc chloride. The product (15) was reduced to the L-fu-citol derivative (16) with Raney nickel. The overall yield of 16 was 29%, and it was characterized as the crystalline 6-p-toluenesulfonate 17. Oxidation of 16 by the Pfitzner-Moffatt reagent55 proceeded readily and, after O-deacetonation, and purification of the product by chromatography on a column of silica gel, L-fucose (18 13% overall yield from D-galactose) and L-fucitol (19 1% yield) were isolated (see Scheme 3). 

Laszlo introduced an oxidative cleavage of dithioacetals by their clayfen (4) and claycop reagents under mild conditions with excellent yields [46, 47]. These reagents are convenient sources of the nitrosonium ion NO+, a soft reactive Lewis acid species, well adapted for attack of the soft sulfur atom. 

Oxidation of a thioacetal at one of the sulfur atoms offers some useful features. After formation of the carbaniun and addition to an electrophilic partner, the hydrolysis is easier than for dithioacetals and can be made with dilute sulfuric or perchloric acid. Moreover, the addition of a lithiated carbanion derived from these species to enones occurs in a 1,4 rather than a 1,2 manner (the usual way for less stabilized more reactive thiocarbanions). The chemistry of these thioacetal monoxides was developed in the 1970s mainly by Ogura and Tsuchihashi [287-290] and by Schlessinger and co-workers [291-293], Two examples of application are given. 

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. 

There is one report in which sulfides are oxidized by PDC in aqueous acetic acid however normally the oxidation of alcohols is quicker, so that selective oxidation of alcohols with PDC is possible in the presence of sulfur containing compounds, such as thiophenes,153 aryl sulfides,154 alkyl sulfides155 and dithioacetals.156... 

The Parikh-Doering oxidation provides a very high regioselectivity for the oxidation of alcohols. Oxidation-sensitive functionalities, like indoles,99a,c sulfides,109 and selenides 110 as well as oxidation-sensitive protecting groups, like dithioacetals,111 PMB104 and dimethoxybenzyl ethers109b, do not react. 

Quite puzzlingly, other authors report the selective oxidation of alcohols in the presence of dithioacetals.40... 

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