Hemithioacetals, hydrolysis

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. 

Thiols, like alcohols, react readily with carbonyl compounds. The resulting hemithioacetals (102), thioacetals (103) and their cyclic analogues (104) and (105) are of considerable synthetic importance. These compounds are more stable to acid hydrolysis than their oxygen analogues but can be hydrolyzed under mild conditions in the presence of metal ions such as Ag(I) (equation 29). The synthetic importance of the metal ion-promoted hydrolyses has led to the publication... 

The most general approach to the synthesis of acyl silanes is based on hydrolysis of 2-silyl-l,3-dithioacetals, first investigated for 1,3-dithiane derivatives by Brook56 and Corey57 in the late 1960s (Scheme 3). Oxathioacetals and protected hemithioacetals have also been used, and some formyl silanes have been isolated by hydrolysis of dioxa-acetals (vide supra). 

The mechanism of these reactions was proposed to take place by initial electron transfer to the carbonyl group of the thioester, generating a ketyl-like radical anion such as 103 (Scheme 7.43). Subsequent radical addition to the electron-deficient alkene (acrylamide or acrylate), possibly guided by pre-complexation to a Sm(III) metal ion, generates a new radical centre, which is reduced to the corresponding Sm(III) enolate by a second equivalent of Sml2. Protonation of this enolate and hydrolysis of the hemithioacetal upon work-up then lead to the y-ketoamide or ester. 

The 2-acetoxysulfides are obtained according reaction (11) by in situ formation of the configurationally unstable hemithioacetals and subsequent lipase-catalyzed acylation. Racemization of the hemithioacetals was achieved by silica gel. The 2-phenylthiocarboxylic acid was formed by hydrolysis of the corresponding thioester in the presence of trioctylamine [reaction (12)]. 

Hydrolysis of hemithioacetals, hemithioketals, and thio- and thia-glycosides Two factors dominate the title process - the low basicity of dicovalent sulphur, which makes protonation and hydrogen bonding more difficult, and the lower ability of sulphur to stabilise an adjacent carbonium ion centre. This is conventionally attributed to poor overlap between the 3p orbital containing the sulphur lone pair and the vacant 2p orbital on carbon (Fig. 12), and is manifested in carbohydrate... 

As expected from the low hydrogen-bonding ability of sulphur, attempts to observe either intra- or inter-molecular general acid catalysis in the hydrolysis of hemithioacetals have met with little success. The only convincing example is compound LXXIV, in which acid catalysis is concerted with nucleophihc attack by the second carboxylate and contributes a rate enhancement of about 10 [177]. 

Above Steps (1) and (2) are peptide chain cleavage, Steps (3) and (4) are thiol formation by hydrolysis. Steps (5) and (6) are hemithioacetal regeneration via cyclization of the thiol. 

There is at present no direct evidence that the enzyme-aldehyde adduct has the proposed structure. However, indirect evidence that the adduct resembles the transition state for substrate hydrolysis comes from studies with elastase in which the relative binding energies of different peptide aldehydes were found to reflect k a/K,n and not the K, for analogous substrates. The proposed structure is also consistent with the finding that the enhanced binding due to the aldehyde group is more marked with the cysteine protease papain than with any serine protease so far studied. This is in accord with the greater stability of hemithioacetals. ... 

For example, the uridine derivative (26) [62]. prepared by the hydrogen chloride-catalyzed addition of ethyl vinyl ether to 5 -0-acetyluiidine 3 -phosphate has been used in oli oribonucleotide synthesis. Other acetal (or more precisely hemithioacetal) systems which have been su ested as protecting groups include tetrahydrothio-furanyl and -pyranyl derivatives (27 and 28, respectively). The latter derivatives, which may be prepared [63] by the acid-catalyzed addition of the corresponding thioenol ethers to alcohols, undergo ready hydrolysis in the presence of silver ion. 

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