Solvolyses of 2-Deoxy-α- and β-d-Glucopyranosyl 4‘-Bromoisoquinolinium Tetrafluoroborates

Abstract

The solvolyses of 2-deoxy-alpha- and beta-D-glucopyranosyl 4'-bromoisoquinolinium tetrafluoroborates (1 and 2) were monitored in aqueous methanol, ethanol, trifluoroethanol, and binary mixtures of ethanol and trifluoroethanol. The observed rate constants are consistent with the solvolyses of 1 and 2 proceeding via dissociative (D(N) A(N)) transition states. In comparison to the alpha-anomer, solvolysis of the beta-compound gives a greater transition state charge delocalization onto the ring oxygen atom. Analysis of the solvolysis product ratios indicates that the 2-deoxyglucosyl oxacarbenium ion is not solvent-equilibrated in the solvent mixtures studied. In the solvolysis of compound 1, the solvent trifluoroethanol facilitates diffusional separation of the leaving group and, in so doing, promotes the formation of the retained trifluoroethyl glycoside.

The Experimental Evidence in Support of Glycosylation Mechanisms at the SN1–SN2 Interface

“…In subsequent work Bennet and coworkers, studying the hydrolyses of 2-deoxy glucopyranosyl pyridinium ions in the presence of added azide arrived at lifetimes of 1.4 × 10 −11 s and 2.7 × 10 −11 s for the ion pair encounter complexes originating from the β- and α-salts, respectively, and concluded that the 2-deoxyglucopyranosyl oxocarbenium ion is not fully solvent equilibrated in water (Table 7). 79,80 Extrapolating the azide clock method to the solvolysis of CMP N -acetyl neuraminate, Horenstein and Brunner determined a lifetime of ≥3 × 10 −11 s at pH 5 for the N -acetyl neuraminate oxocarbenium ion (Table 7), and concluded that the α-carboxylate stabilizes the oxocarbenium ion. 81 This latter suggestion is in agreement with Horenstein’s early computational work in which it was found that the α-carboxylate stabilizes the oxocarbenium ion electrostatically by 110 kcal.mol −1 relative to the carboxylic acid in the gas phase, but only by 17 kcal.mol −1 in water.…”

Aspects of Glycosidic Bond Formation in Aqueous Solution: Chemical Bonding and the Role of Water

“…Simple sugars make up a wide variety of substances found in nature, from DNA to cellulose to biological energy storage mechanisms. Consequently, the glycosidic bond has been studied experimentally for a wide variety of compounds, [1][2][3][4][5][6][7][8][9][10][11][12][13] predominantly through hydrolysis, under a myriad of conditions, and is important in the consideration of enzymatic glycosyl-transfer reactions. One of the reasons it has been studied so extensively is because of the rich and often subtle variety of the reactions that take place.…”

“…Adding to the complexity are competing hydrolysis reactions when multiple products are possible. [1] It is accepted that the reaction proceeds through an oxocarbenium cation intermediate; the mechanism involved in hydrolysis of glucopyranosides has been concluded to be dissociative (D N +A N ) or partially-dissociative (A * N D N ) [1,2,13] which lies between S N 2 and S N 1 behavior, although a concerted mechanism (A N D N ) [5,6] has been observed for the case of aqueous hydrolysis of fluoro-a-d-glucopyranoside (see ref. [14,15] for notation details).…”

Structural and solvent effects on rates of solvolysis of secondary alkyl substrates—an update

“…21 Secondary alkyl cations lacking stablizing groups such as 2-adamantyl will have shorter lifetimes; even the resonance-stabilized secondary 2-deoxyglucosyl oxacarbenium ion may not be solvent equilibrated in typical alcoholic solvolysis media. 22 Short or negligible lifetimes of cations formed during the solvolysis of unactivated secondary substrates are probably the main factor underlying a long-running controversy: 6,20 e.g. does 18 O scrambling of oxygen in 'unreacted' sulfonates indicate ion pair return on the main reaction pathway 20 or a side reaction via a concerted polar mechanism?…”