Dithioacetals carbonyl group protection

The chemical transformations of dialkyl dithioacetals have been reviewed in detail [47] and offer routes to a variety of useful carbohydrate derivatives. Dialkyl dithioacetal derivatives of sugars continue to play an important role in modem synthetic carbohydrate chemistry through reactions of die dithioacetal function and manipulation of the sugar hydroxyl groups. Dithioacetals also provide a convenient method for temporary protection of sugar carbonyl groups in the synthesis of noncarbohydrate natural products. 

Methylene derivatives, substituted, to protect carbonyl groups, 217 5-Methylene-l,3-dioxanes, to protect carbonyl groups, 186-187 S,S -Methylene dithioacetals, to protect S,Sr-dithiols, 305... 

Similar prolonged ethanethiolysis of D-mannopyranosylstreptomycin 46) produced ethyl 1-thio-a- and -jS-D-mannopyranosides, isolated as acetates. Likewise, streptomycin was cleaved with ethanethiol and hydrochloric acid 47) to produce ethyl 1-thiostreptobiosaminide diethyl dithioacetal hydrochloride. This type of cleavage is useful in structure determination since the carbonyls are protected with thioacetal groups as they are released 4S). It was by means of this reaction that the nature of the acid-sensitive strep-tose portion of streptomycin was elucidated. (See Chapter X.)... 

Dithioacetals of reducing sugars are obtained by reaction with a dithiol, such as ethane dithiol, and zinc chloride [37] (reaction 4.38). The acetylated dithioacetal can be desulfurized by cartalytic reduction using Raney nickel to reduce the carbonyl group to a hydrocarbon [38] (reaction 4.38). The 1,1-dithioacetal can be used to reversibly protect the aldehyde group, since it can be readily removed by acid hydrolysis. 

Dithioacetals are useful in organic synthesis as protective groups for carbonyl compounds, as precursors of acyl carbanion equivalents or as electrophiles under Lewis acidic conditions. The DBSA-catalysed system was also found to be applicable to dithioacetal-ization in water. In addition, easy work-up has been realized without the use of organic solvents when the products are solid and insoluble in water. In fact, the dithioacetaliza-tion of cinnamaldehyde on 10 mmol-scale with 1 mol% of DBSA proceeded smoothly to deposit crystals. The pure product was obtained in excellent yield after the crystals were filtered and washed with water (Equation (8)). This simple procedure is one of the advantages of the present reaction system. 

The electrochemical deprotection of carbonyl compounds proved to be a useful method especially in cases where alternative chemical reactions are unsuccessful, a-Keto- and a-hydroxythioacetals, when oxidized in MeCN-HoO (9 1 v/v) on a Pt anode, are transformed into the corresponding a-diones and a-ketols [142]. Diethyl dithioacetals of sugars were anodically oxidized in MeCN-H20 (5% H2O) on Pt electrode, and the substrates were successfully deprotected producing the correspondent carbohydrates in 65-85% yield [143]. It is noteworthy that protected hydroxy groups as esters or cyclic acetals were not affected. Selective deprotection to carbonyl compounds electrooxidizing mixtures of thioacetals, like a ketone and an aldehyde thioacetal, the former being preferentially deprotected, was described [144]. 

Additional examples of synthetic application of periodic acid as an oxidant include the oxidative iodination of aromatic compounds [1336-1341], iodohydrin formation by treatment of alkenes with periodic acid and sodium bisulfate [1342], oxidative cleavage of protecting groups (e.g., cyclic acetals, oxathioacetals and dithioacetals) [1315, 1343], conversion of ketone and aldehyde oximes into the corresponding carbonyl compounds [1344], oxidative cleavage of tetrahydrofuran-substituted alcohols to -y-lactones in the presence of catalytic PCC [1345] and direct synthesis of nitriles from alcohols or aldehydes using HsIOe/KI in aqueous ammonia [1346],... 

The formation of a dithioacetal as an intermediate in organic synthesis is not new to most chemists. However, in recent years there has been a continuing improvement in the methods of preparation as well as the subsequent reactions. The early use of the dithioacetal group as a means to reduce carbonyl functions with Raney nickel has been expanded to extensive use as a protecting group, methylene blocking group and as an intermediate in the preparation of complex hydrocarbons, olefins, aldehydes and ketones. 

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