Hydrolysis thioacetals

According to Panek et al.39 thioacetals are hydrolyzed under the action of Dess-Martin periodinane, being possible to perform a selective hydrolysis without affecting an alcohol present in the same molecule. Reaction conditions optimized for the thioacetal hydrolysis involve the use of Dess-Martin periodinane in a MeCN/CH2Cl2/H20 (8 1 1) solvent mixture. Under these conditions, Dess-Martin periodinane behaves as a very efficient reagent for the hydrolysis of thioacetals in complex substrates. 

Acid-catalyzed thioacetal hydrolysis Preliminary examination ... 

Nucleophilic displacement of iodide with thioacetate in the secosteroid 464 and subsequent simultaneous formate and thioacetate hydrolysis with concomitant cyclization provides the thiopyran ring four further steps are required to afford the 6-thiaallopregnanolone 465 (Scheme 159) <2006T4762>. 

Chiral -amino acyl silanes have been prepared throngh the addition of 2-lithio-2-trimethylsilyl-l,3-dithiane to enantiomaicaUy pure iV-tosylaziridines followed by mercury-mediated thioacetal hydrolysis. ... 

Lithiated dithiane 35 is another example of a formyl anion equivalent. Acylation would provide 36 and thioacetal hydrolysis would provide 29. The thioacetal hydrolysis is the FGT that establishes the equivalency. Acylation of dimsyl anion 37 (from metallation of DMSO) would afford )8-ketosulfoxide 38. Once again an oxidation is needed to establish the desired equivalency. This can be accomplished using a Pummerer rearrangement wherein oxidation occurs at carbon with reduction at sulfur. Hydrolysis of the resulting S,0-acetal would complete the required FGT. 

In Summary Acetals and thioacetals are useful protecting groups for aldehydes and ketones. Acetals are formed under acidic conditions and are stable toward bases and nucleophiles. They are hydrolyzed by aqueous acid. Thioacetals are usually prepared using Lewis acid catalysts and are stable to both aqueous base and acid. Mercuric salts are required for thioacetal hydrolysis. Thioacetals may also be desulfurized to hydrocarbons with Raney nickel. 

Note that thioacetals are not easily deprotected using aqueous Bronsted acids sulfur is much less easily protonated than oxygen. The normal conditions for thioacetal hydrolysis employ catalysis. 

The mechanisms for hydrolysis of 0,5-acetals have been reviewed. The following acid-catalyzed cleavage rates show that the 0,5-acetals have a stability that lies between thioacetals and acetals ... 

The aldehyde function at C-85 in 25 is unmasked by oxidative hydrolysis of the thioacetal group (I2, NaHCOs) (98 % yield), and the resulting aldehyde 26 is coupled to Z-iodoolefin 10 by a NiCh/CrCH-mediated process to afford a ca. 3 2 mixture of diaste-reoisomeric allylic alcohols 27, epimeric at C-85 (90 % yield). The low stereoselectivity of this coupling reaction is, of course, inconsequential, since the next operation involves oxidation [pyridinium dichromate (PDC)] to the corresponding enone and. olefination with methylene triphenylphosphorane to furnish the desired diene system (70-75% overall yield from dithioacetal 9). Deprotection of the C-77 primary hydroxyl group by mild acid hydrolysis (PPTS, MeOH-ClHhCh), followed by Swem oxidation, then leads to the C77-C115 aldehyde 28 in excellent overall yield. 

The addition reactions of alkyllithium-lithium bromide complexes to a-trimethylsilyl vinyl sulfones that have as a chiral auxiliary a y-mono-thioacetal moiety derived from ( + )-camphor are highly diastereoselective. A transition state that involves chelation of the organolithium reagent to the oxygen of the thioacetal moiety has been invoked. The adducts are readily converted via hydrolysis, to chiral a-substituted aldehydes22. 

The 2- and 3-halogenoquinoxalines may be converted into the corresponding quinoxalinethiones by treatment with sodium hydrogen sulfide, sodium thiosulfate, thioacetic acid (with concomitant decarboxylation), or (indirectly) by treatment with thiourea followed by alkaline hydrolysis of the thiouronio intermediate (usually as a one-pot procedure). The same substrates furnish corresponding alkylthio-, arylthio-, or arylsulfonylquinoxalines by treatment with a salt of the appropriate alkanethiol, thiophenol, or benzenesulfinic acid. The following classified examples illustrate such processes. 

Because 2-trimethylsilyloxy sulfides such as 1154 and 1157 are hemiphenyl thioacetals of aldehydes, they are readily hydrolyzed to aldehydes [8-12] or ketones [13]. Thus alkylation of the lithium salt 1162 with cyclohexyhnethylbromide 1163, gives in nearly quantitative yield, the sulfide 1164, which, after oxidation with m-chloroperbenzoic acid and hydrolysis, rearranges in 70% yield to cyclohexylacetal-dehyde 1165 [8] (Scheme 8.2). A more detailed discussion of the formation of aldehydes is given in Section 8.5. 

C. Moreau, J. Lecomte, S. Mseddi, and N. Zmimita, Stereoelectronic effects in hydrolysis and hydrogenolysis of acetals and thioacetals in the presence of heterogeneous catalysts, J. Mol. Catal. A Chem., 125 (1997) 143-149. 

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... 

However, the switchover from an A2 to an A1 hydrolysis is a very common mechanistic pathway in strong acid media, probably more common than the pure A2 mechanism. Excess acidity analyses have shown that thioacetic acid, several thiobenzoic acids, and many thiolbenzoate and thionbenzoate esters show this sort of mechanism switch.179 Acylals and thioacylals also show this behavior,116 with thioacylals using two water molecules and acylals one. Many hydroxamic acids react this way,127,216 as do esters of various types,41,217,218 episulfoxides219 and aryloxatriazoles.220 Acylhydrazines can also show a mechanism switch of this sort, although with these substrates the situation is somewhat more complex.221... 

The reaction of titanocene-alkylidenes generated from thioacetals with nitriles followed by hydrolysis affords ketones. Like the reaction of titanocene-methylidene, this reaction may proceed via the azatitanacydobutene 87 and/or the vinylimido complex 88, which reacts with an organic halide to form an a-substituted ketone [80] (Scheme 14.37). 

A somewhat similar configurational correlation between (leva)-glyceraldehyde and (dexfro)-lactic acid has been made by Wolfrom, Lemieux, Olin and Weisblat.36 Reductive desulfurization of tetra-acetyl-2-methyl-D-glucose diethyl thioacetal (XXVII) and hydrolysis of the product gave 2-methyl-l-desoxy-D-glucitol (XXVIII) oxidation... 

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