Hemithio acetals

The most widely used protective groups for aliphatic and alicyclic aldehydes and ketones are (a) cyclic acetals and (b) cyclic dithioacetals and hemithio-acetals. The use of semicarbazones, oximes and 2,4-dinitrophenylhydrazones (for preparation see Section 9.6.13, p. 1257) is less common but has found application in certain instances where the more vigorous methods required for deprotection are not detrimental. 

Hemithioacetals may be transformed in two ways with Raney Ni. The sulfur group may be removed with the oxygen group intact as in eq. 13.78 or desurfiirized to recover the parent carbonyl compounds. In the ethylenehemithio acetal of a ketone, since the oxo group can be recovered by treatment with Raney Ni, this reaction makes it possible to use the hemithio acetal as a protective group for the carbonyl group (eq. 13.79). 

Desulfurization of a hemithio acetal as in eq. 13.78 has often been utilized in carbohydrate chemistry. As an example, 2,-naphthyl l-thio- 3-D-ribopyranoside tribenzoate was converted to 2,3,4-tribenzoyl-l,5-anhydroribitol in a good yield (eq. 13.80).156 The desulfurization may be performed without protecting the alcoholic hydroxyl groups.157,158... 

Androstene-3,17-dione can be transformed selectively into the 17-ethylenehemithio acetal in the presence of the a,P-unsaturated carbonyl system. The parent andros-tenedione can be regenerated by treatment of the hemithio acetal with Raney Ni (eq. 13.82) by the reaction of eq. 13.79.160... 

Oxidative hydrolysis of 2-alkyl- and 2-acyl-l,3-dithians by iV-halogeno-succinimides is recommended as a high-yield method of carbonyl regeneration the combination of iV-chlorosuccinimide and silver(i) ion is suitable for reaction with unsaturated 1,3-dithians. In a related oxidative procedure, ketones and aldehydes can be readily regenerated from their ethylene thio- or hemithio-acetals by treatment with aqueous chloramine-T. 

Addition of hydrogen sulfide and thiols is qualitatively similar to reaction with alcohols in that there are two stages, formation of hemithioacetal (or hemithio-ketal) followed by acid-catalyzed elimination of the hydroxy group and substitution of a second —SR (Equations 8.47 and 8.48). The transformation has been studied less extensively than hydration and acetal formation, and relatively little information on mechanism is available. The initial addition appears to be specific base-catalyzed, an observation that implies that RS is the species that adds. The situation is thus similar to cyanide addition. General acid catalysis has, however, been found at pH 1 to 2 for addition of weakly acidic alkyl thiols, and the reaction rate as a function of pH has a minimum and rises both on the... 

TABLE 9.2. Hemithio- and Dithio-Acetals and -Ketals Representative Examples of Preparation, and Use as Protective Groups... 

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