Acetolysis of glycosides

the energies of transition state intermediates for the hydrolysis of a- and P-D-glycopyranosides 80 and 81 must be very close, as shown in Fig. 3.24. 

It was established that both transition states are late and have essentially the same oxocarbenium ion in which the MeOH is at the long distance from the Cl carbon ( 1.80 A). What happens is while the MeOH is leaving, the H2O is entering (SN2-like reaction). But one should realize that TS energy is lowered by the fact that at TS, there is a p-orbital on 05 that assists this Sn2 reaction. Thus, the anomeric effect still plays the same key role. In that case, the competing TS resemble 87 and 88 (Fig. 3.24) which again have to have very close energy. 

The cleavage of a glycosidic bond by acetolysis is an alternative method to hydrolysis. Although both methods are acid-catalyzed, and presumably in the case of glycopyranosides involve the formation of a cyclic oxocarbenium transition state, they also have their differences. Thus, for example, the most important difference is that the hydrolysis is always performed either in aqueous solutions or in a solvent containing water, whereas the acetolysis is performed in nonaqueous 

A review on acetolysis has been published by Guthrie and McCarthy [73]. 

The mechanism of acid-catalyzed cleavage of glycosidic bonds could be perhaps better understood by studying the mechanism of acetolysis, since the acetolysis is performed in the absence of water (most often in acetic anhydride), and thus, the electronic effects that exist in each glycopyranoside structure will not be 

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Many rearrangement reactions are initiated by BF3 complexes in the presence of acetic anhydride, including the synthesis of functionalized and optically active pyrans from (+)-(/ ,R)-diethyl tartrate (Eq. 41) [74]. Other examples include the conversion of bicyclic into monocyclic [75] and tricyclic into bicyclic systems [76], the acetolysis of glycosides resulting in the formation of the fully acetylated acyclic derivative [77], and the unusual migration of nitrogen in the dienone-phenol rearrangement of an N-methoxy-/ -lactam [78]. 

From the synthetic standpoint, the acetolysis of glycoside derivatives to the corresponding peracetates, followed by deacetylation, has been used in the synthesis of a wide variety of derivatives of free sugars (see, for example, Refs. 22 and 37-41). 

Formolysis and acetolysis are not common methods for cleavage of glycosidic linkages. They do have some unique applications, however. For instance, methylated polysaccharides are not generally soluble in hot water, and consequently, hydrolysis is best preceded by formolysis under these circumstances. For example, 5 mg of methylated polysaccharide is dissolved in 3 mL of 90% formic acid, and the solution is kept for 2 h at 100°. The formic acid is removed by evaporation at 40°. The residue is dissolved in 1 mL of 250 mM sulfuric acid and the solution is heated for 12 h at 100°, cooled, the acid neutralized with barium carbonate, the... 

Systematic studies of the acetolysis of disaccharides have been performed.57-803 Lindberg81,82 showed that anomerization and acetolysis of acetylated glycosides is retarded by the presence of electronegative groups in the aglycon. A mechanism involving an acyclic intermediate (20) was proposed for these reactions (see Scheme 2). 

C. J. Lawson and D. A. Rees, Carrageenans. Part VI. Reinvestigation of the acetolysis products of X-carrageenan, revision of the structure of a-l,3-galactotriose , and a further example of the reverse specificities of glycoside hydrolysis and acetolysis, J. Chem. Soc. C (1968) 1301-1304. 

Mechanistic studies on acid hydrolysis of glycosides often encounter the endolexo-cycWc cleavage problem [13]. For instance, the sulfuric acid (l%)-catalyzed acetolysis of the... 

It has been shown that the acetolysis of methyl tri-0-acetyl-/S-D-arabino-pyranoside, when catalyzed with zinc chloride or 0.16% sulfuric acid, provides a mixture of the two isomeric penta-O-acetyl-n-arabinose methyl hemiacetals in good yield.This reaction provides good evidence for the cleavage of the cyclized bond in preference to that of the glycosidic group. 

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