Hemithioacetal

Alkyl halides and sulfonates are the most frequently used alkylating acceptor synthons. The carbonyl group is used as the classical a -synthon. O-Silylated hemithioacetals (T.H. Chan, 1976) and fomic acid orthoesters are examples for less common a -synthons. In most synthetic reactions carbon atoms with a partial positive charge (= positively polarized carbon) are involved. More reactive, "free carbocations as occurring in Friedel-Crafts type alkylations and acylations are of comparably limited synthetic value, because they tend to react non-selectively. 

A new, versatile and selective synthesis of 6- and 7-substituted pteridines was reported by Rosowsky (73JOC2073). /3-Keto sulfoxides, which can be viewed as latent a keto aldehydes, react with (251) to give 6-substituted pterins, and the use of a-keto aldehyde hemithioacetals leads in a regiospecific synthesis to the isomeric 7-substituted pterins (equation 85). 

The product is a hemithioacetal. In the rate-determining step, the general acid HA donates a proton to the carbonyl oxygen, thus assisting the nucleophilic attack of the thiol on the carbonyl carbon. 

The enamine double bond attacks a sulfur atom of lipoamide and carries out an S j2-like displacement of the second sulfur to yield a hemithioacetal. 

Elimination of thiamin diphosphate ylide from the hemithioacetal intermediate yields acetyl dihydrolipoamide. .. 

Step 4 of Figure 29.11 Elimination of Thiamin Diphosphate The product of the HETPP reaction with lipoamide is a hemithioacetal, which eliminates thiamin diphosphate vlide. This elimination is the reverse of the ketone addition in step 1 and generates acetyl dihydrolipoamide. 

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Analogous with the rearrangement of allylic sulfoxides is the [2,3]-sigmatropic rearrangement of propargylic sulfoxides to allenic sulfenates. This process, which has been relatively little studied so far, appears to be the first step in the facile and quantitative rearrangement of sulfoxide 98 to the hemithioacetal 101 (equation 45)167. This reaction,... 

Carb-29. Hemiacetals and hemithioacetals 2-Carb-30. Acetals, ketals and their thio analogues 2-Carb-31. Names for monosaccharide residues... 

Racemization of some substrates can take place through reversible formation of the substrate via an addition/elimination process. The racemization can be acid or base catalyzed. In this section we vill discuss DKR of cyanohydrins and hemithioacetals. 

As in the case discussed above, hemithioacetals can be racemized by elimination/ addition of a small molecule (a thiol in this case) under weak acidic conditions. Rayner et al. reported the first example of DKR of this kind of substrates yielding homochiral a-acetoxysulfides (Figure 4.24) [49]. 

To direct a solvolytic ring opening, 2-methoxycyclopropyllithium (6) was developed as a chain extension conjunctive reagent. The failure of P-elimination to occur in 6 presumably derives from the high strain of cyclopropene and poor orbital overlap for elimination. The aldehyde adducts smoothly solvolyze to give p,Y unsaturated aldehydes (Eq. 22) 23) which are best initially isolated as their hemithioacetals. 

Beedle, A. S., Munday, K. A., Wilton, D. C. The stereochemistry of the reduction of mevaldic acid-coenzyme A hemithioacetal by rat liver 3-hydroxy-3-methylglutaryl coenzyme A-reductase. FEBS Letters 28, 13—15 (1972). 

The electroreduction of disulfides R2S2 (R = Ar, Aik), in the presence of carbonyl compounds and MesSiCl, includes the formation of intermediate thiosilanes and results in trimethylsilyl ethers of hemithioacetals of ketones and aldehydes or in full thioacetals depending on whether a two-compartment (a) or an undivided (b) cell was used (Scheme 48) [218]. 

Scheme 48 Hemithioacetals and thioacetals via reduction of disulfides in the presence of ketone.

The statins, e.g. pravastatin, are a group of HMGR inhibitors that possess functionalities that mimic the half-reduced substrate mevaldate hemithioacetal. The affinity of these agents towards HMG-CoA reductase is some 10" -fold more than the natural substrate, making them extremely effective inhibitors of the enzyme, and powerful drugs in coronary care. 

Thus the cyclopropanone hydrate 21 is an inhibitor of yeast aldehyde dehydrogenase (ALDH) through the nucleophilic substitution of a hydroxyl group by an enzymic thiol 47 leading to the cyclopropanone hemithioacetal 24 a, Eq. (16) [211. 

The reaction of BTSP with Li derivatives of sulfides and nitriles gives the corresponding O-trimethylsilyl hemithioacetal and cyanohydrins (equation 49). 

Hydrolysis of cyclic dithioaeetals and hemithioacetals This reaction can be effected in good yield with HgO and 35% aqueous HBF4 in THF in 5-10 minutes. This method is usually more effective than use of HgO-BF3 etherate (3, 136). It is useful for hydrolysis of compounds 1-4 to give the corresponding aldehydes or ketones in 80-100% yield. 

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