A Mechanism for the Anomerization of Acetylated Alkyl Glycopyranosides

Lemieux, R. U.; Shyluk, W. P.

doi:10.1139/v55-015

Cited by 21 publications

(5 citation statements)

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“…Anomerization can be useful in stereoselective glycoside synthesis as it leads to the thermodynamically stable stereoisomer . The 1,2-trans glycoside is often isolated in reactions with 2-acyl containing donors using TiCl 4 or SnCl 4 , a fact usually explained by acyl group participation. Yet, on some occasions the α-product or a mixture of α- and β-products is obtained from such glycosidation reactions.…”

Section: Introductionmentioning

confidence: 99%

SnCl₄- and TiCl₄-Catalyzed Anomerization of Acylated O- and S-Glycosides: Analysis of Factors That Lead to Higher α:β Anomer Ratios and Reaction Rates

Pilgrim

Murphy

2010

J. Org. Chem.

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The quantification of factors that influence both rates and stereoselectivity of anomerization reactions catalyzed by SnCl(4) and TiCl(4) and how this has informed the synthesis of α-O- and α-S-glycolipids is discussed. The SnCl(4)-catalyzed anomerization reactions of β-S- and β-O-glycosides of 18 substrates followed first order equilibrium kinetics and k(f) + k(r) values were obtained, where k(f) is the rate constant for the forward reaction (β → α) and k(r) is the rate constant for the reverse reaction (α → β). Comparison of the k(f) + k(r) values showed that reactions of glucuronic acid or galacturonic acid derivatives were ∼10 to 3000 times faster than those of related glucoside and galactopyranoside counterparts and α:β ratios were generally also higher. Stereoelectronic effects contributed from galacto-configured compounds were up to 2-fold faster than those of corresponding glucosides. The introduction of groups, including protecting groups, which are increasingly electron releasing generally led to rate enhancements. The anomerization of S-glycosides was consistently faster than that of corresponding O-glycosides. Reactions were generally faster for reactions with TiCl(4) than those with SnCl(4). Anomeric ratios depended on the Lewis acid, the number equivalents of the Lewis acid, temperature, and substrate. Very high ratios of α-products for both O- and S-glucuronides were observed for reactions promoted by TiCl(4); for these substrates TiCl(4) was superior to SnCl(4). Anomeric ratios from anomerization of S-glucosides were higher with SnCl(4) than with TiCl(4). The dependence of equilibrium ratio on Lewis acid and the number of equivalents of Lewis acid indicated that the equilibrium ratio is determined by a complex of the saccharide residue bound to the Lewis acid and not the free glycoside. The high α:β ratios observed for anomerization of both O- and S-glycuronic acids can be explained by coordination of the C-1 heteroatom and C-6 carbonyl group of the product to the Lewis acid, which would enhance the anomeric effect by increasing the electron-withdrawing ability of the anomeric substituent and lead to an increase in the proportion of the α-anomer. Such an observation would argue against the existence of a reverse anomeric effect. Support for a chelation-induced endocyclic cleavage mechanism for the anomerization is provided by the trapping of a key intermediate. The data herein will help predict the tendency of β-glycosides to undergo anomerization; this includes cases where 1,2-trans glycosides are initial products of glycosidation reactions catalyzed by TiCl(4) or SnCl(4).

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Section: Introductionmentioning

confidence: 99%

SnCl₄- and TiCl₄-Catalyzed Anomerization of Acylated O- and S-Glycosides: Analysis of Factors That Lead to Higher α:β Anomer Ratios and Reaction Rates

Pilgrim

Murphy

2010

J. Org. Chem.

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“…[25][26][27][28][29][30] The question whether this reaction proceeds by an intramolecular process was investigated by Lemieux and Shyluk who anomerized a racemic mixture of 14 C-labeled methyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside and unlabeled methyl 2,3,4,6-tetra-O-acetyl-β-L-glucopyranoside with TiCl 4 . 29 The method of isotopic dilution showed that the radioactivity was exclusively located in the D-enantiomer and thus gave evidence for an intramolecular process. Several mechanisms have been proposed.…”

Section: Resultsmentioning

confidence: 99%

“…In contrast to these reactions, the action of TiCl 4 on alkyl β-glycosides does not produce glycosyl chlorides but causes anomerization to the α-anomers. − The question whether this reaction proceeds by an intramolecular process was investigated by Lemieux and Shyluk who anomerized a racemic mixture of 14 C-labeled methyl 2,3,4,6-tetra- O -acetyl-β- d -glucopyranoside and unlabeled methyl 2,3,4,6-tetra- O -acetyl-β- l -glucopyranoside with TiCl 4 . The method of isotopic dilution showed that the radioactivity was exclusively located in the d -enantiomer and thus gave evidence for an intramolecular process.…”

Section: Resultsmentioning

confidence: 99%

Bifunctional Building Blocks for Glyco-Architectures by TiCl₄-Promoted Ring Opening of Cyclodextrin Derivatives

Bösch

Mischnick

2007

Biomacromolecules

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During our studies on the preparation of blocklike substituted 1,4-glucans by cationic ring-opening polymerization,1,2 we found that TiCl4 behaves differently from common initiators like Et3O+X- (X = PF6, SbCl6), BF3.Et2O, or methyl triflate, causing only ring opening under formation of alpha-maltooligosyl chlorides bearing one free hydroxyl group (4-OH) at the nonreducing end. These compounds are valuable building blocks for the preparation of new glyco-architectures since they are easily accessible starting materials for direct glycosylations or the preparation of a variety of oligomeric glycosyl donors like alkyl glycosides, thioglycosides, or azides. We successfully carried out and optimized the TiCl4-promoted ring opening with per-O-methylated, per-O-ethylated, and temporarily protected per-O-allylated cyclodextrins of various ring size. 1H NMR spectroscopy and high-pressure liquid chromatography-evaporative light-scattering detection (HPLC-ELSD) were used to characterize the products.

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“…The methods used to prepare the radioactive compounds have already beell described (8,12). The isotopic dilution analyses were carried out by adding weighed amounts, about 10 mgm., of the radioactive compounds t o a weighed sample of the reaction product before chromatographic separation, purifying the compounds from the chromatogram by several recrystallizations, and then determining the radioactivities of the pure compound as was described in a previous communication (9).…”

Section: Methodsmentioning

confidence: 99%

THE ACETOLYSES OF THEALPHAANDBETAMETHYLD-GLUCOPYRANOSIDE TETRAACETATES

Lemieux¹,

Shyluk²,

Huber³

1955

Can. J. Chem.

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The acetolyses of the alpha and beta methyl D-glucopyranoside tetraacetates in 1 : 1 acetic acid -acetic anhydride 0.5 11d with respect to sulphuric acid were followed a t 25'C. by isotopic dilution analysis of products isolated after various intervals of tirne. The reaction of the a-glucoside was found to proceed mainly with inversion of the anomeric center. On the other hand, the 0-glucoside was found to undergo acetolysis with retention of configuration concurrent with anomerization. I t was shown t h a t the polarimetric changes observed in the course of the reactions could be satisfactorily accounted for on the basis of these reaction routes. Reaction mechanisms are suggested. Montgomery et al. (15) investigated the use of either sulphuric acid or zinc chloride in acetic acid -acetic anhydride as a reagent for the acetolysis of glycosides. I t was shown that in many cases the glycoside was converted to a mixture of the anomeric sugar acetates in high yield and the procedure has been widely used for the cleavage of acetal bonds in carbohydrate chemistry. Studies on the acetolysis of the anomeric methyl D-arabinopyranoside triacetates showecl these reactions to be highly complex (15). A solution a t 20°C.of nlethyl a-D-arabinopyranoside triacetate in a mixture of 4y0 sulphuric acid in 7 : 3 acetic anhydride -acetic acid changed sharply in specific rotation from -lgO to -114O in one minute and declined to an equilibrium value of -ZO a t the end of 20 min. The hexaacetate of aldel~ydo-D-arabinose and p-D-arabinopyranose tetraacetate were isolated in yields of soy0 and 12%, 1-espectively, from the product. However, when the experiment was interrupted a t the rotation peak of -114", a 14% yield of methyl /3-D-arabinopyi-anoside triacetate was obtained. Thus, it was apparent that the rapid initial rise in rotation was d~~e to the anomerization of the a-anoiner to the more stable /3-form. This possibility was strengthenecl by the observ a t' loll that ~nethyl @-D-arabinopyranosicle triacetate under the same conditions gave a solution which changed in specific rotation from -184' t o a constant equilibrium value of -17" in three minutes. The hcxaacetate and the p-tetraacetate could be isolated in 56y0 and 11% yields, respectively, after 24 hr. The occurrence of the hexaacetate in the reaction products suggested that the C1 to ring-oxygen bond may cleave in preference to the C1 to methoxyl group bond. This idea was substantiated by the acetolysis of the p-arabinoside under the milder conditions of O.l6Y0 sulphuric acid in 7 : 3 acetic anhydride -acetic acid mixture. Both the anomeric forms of methyl hemiacetal pentaacetates (I) were isolated in good and approximately equal yields. I t is to be notecl that liLl~nz~script received September 7 , 1954 More recently, Lindberg (1, 2, 13) has obtained further evidence that the acetolysis of an unstable 0-acetylated allcyl glycopyranoside is accompanied by anomerization. This was shown to be so for a variety of glucosides (13), galactosides ( I ) , and a xyloside (2...

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A Mechanism for the Anomerization of Acetylated Alkyl Glycopyranosides

Cited by 21 publications

References 13 publications

SnCl₄- and TiCl₄-Catalyzed Anomerization of Acylated O- and S-Glycosides: Analysis of Factors That Lead to Higher α:β Anomer Ratios and Reaction Rates

SnCl₄- and TiCl₄-Catalyzed Anomerization of Acylated O- and S-Glycosides: Analysis of Factors That Lead to Higher α:β Anomer Ratios and Reaction Rates

Bifunctional Building Blocks for Glyco-Architectures by TiCl₄-Promoted Ring Opening of Cyclodextrin Derivatives

THE ACETOLYSES OF THEALPHAANDBETAMETHYLD-GLUCOPYRANOSIDE TETRAACETATES

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A Mechanism for the Anomerization of Acetylated Alkyl Glycopyranosides

Cited by 21 publications

References 13 publications

SnCl4- and TiCl4-Catalyzed Anomerization of Acylated O- and S-Glycosides: Analysis of Factors That Lead to Higher α:β Anomer Ratios and Reaction Rates

SnCl4- and TiCl4-Catalyzed Anomerization of Acylated O- and S-Glycosides: Analysis of Factors That Lead to Higher α:β Anomer Ratios and Reaction Rates

Bifunctional Building Blocks for Glyco-Architectures by TiCl4-Promoted Ring Opening of Cyclodextrin Derivatives

THE ACETOLYSES OF THEALPHAANDBETAMETHYLD-GLUCOPYRANOSIDE TETRAACETATES

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SnCl₄- and TiCl₄-Catalyzed Anomerization of Acylated O- and S-Glycosides: Analysis of Factors That Lead to Higher α:β Anomer Ratios and Reaction Rates

SnCl₄- and TiCl₄-Catalyzed Anomerization of Acylated O- and S-Glycosides: Analysis of Factors That Lead to Higher α:β Anomer Ratios and Reaction Rates

Bifunctional Building Blocks for Glyco-Architectures by TiCl₄-Promoted Ring Opening of Cyclodextrin Derivatives