Effect of 2-O-Benzoyl para-Substituents on Glycosylation Rates

Abstract

From a series of competition experiments, we have explored the degree to which various para-substituents (CN, Br, H, OMe, pyrrolidino) of a 2- O -benzoyl functionalized glucosyl donor of the thioglycoside type affect the rate of glycosylation under N -iodosuccinimide/triflic acid activation. As expected, electron-withdrawing groups were found to decrease the rate of glycosylation, whereas electron-donating groups resulted in the opposite outcome, underscoring the influence on the reaction rate exerted by a participating group. On this basis, a Hammett linear free-energy relationship was established ( R 2 = 0.979, ρ = 0.6), offering fundamental insight into the magnitude of anchimeric assistance in glycosylation chemistry.

Mechanisms of Stereodirecting Participation and Ester Migration from Near and Far in Glycosylation and Related Reactions

“…To probe the intervention of anchimeric assistance in the activation of phenyl 3,4,6-tri- O -benzyl-2- O -benzoyl-β- d -glucopyranosides, shown above to be less reactive than the corresponding tetra- O -benzyl donors on activation with NIS and triflic anhydride at low temperature, Jensen and co-workers studied the relative rates of activation of a series of p -substituted 2- O -benzoates by competition methods . In the series of compounds studied, only the 2- O -(4-pyrrolidino­benzoyl) system was more reactive than the corresponding per- O -benzyl-protected donor.…”

“…Nevertheless, the negative log 10 of the relative rate constant ratios displayed a linear correlation with the Hammett σ p constant indicative of the buildup of positive charge on the ester moiety during the rate-determining step, and so strongly supportive of anchimeric assistance (Figure ). The possibility that the observed trend arose from the difference in electron-withdrawing abilities of the different esters as opposed to anchimeric assistance was discarded on the grounds that the observed trends were much greater in the 1,2- trans -series than in the corresponding 1,2- cis -series where anchimeric assistance is not possible …”

“…To probe the intervention of anchimeric assistance in the activation of phenyl 3,4,6-tri-O-benzyl-2-O-benzoyl-β-D-glucopyranosides, shown above to be less reactive than the corresponding tetra-O-benzyl donors on activation with NIS and triflic anhydride at low temperature, Jensen and co-workers studied the relative rates of activation of a series of p-substituted 2-O-benzoates by competition methods. 147 In the series of compounds studied, only the 2-O-(4-pyrrolidinobenzoyl) system was more reactive than the corresponding per-Obenzyl-protected donor. Nevertheless, the negative log 10 of the relative rate constant ratios displayed a linear correlation with the Hammett σ p constant indicative of the buildup of positive charge on the ester moiety during the rate-determining step, and so strongly supportive of anchimeric assistance (Figure 20).…”

Characterization of glycosyl dioxolenium ions and their role in glycosylation reactions

“…The most common approach to chemically create glycosidic bonds is a nucleophilic substitution reaction between a glycosyl donor carrying an anomeric leaving group, and a glycosyl acceptor containing a nucleophilic alcohol. The stereochemical outcome of glycosylation reactions can be controlled using neighboring group participation (NGP) 5,6 . Acyl groups at the C-2 position of glycosyl donors can engage in NGP affording bicyclic C-1,C-2 dioxolenium ion intermediates that react in a stereospecific manner with glycosyl acceptors to afford 1,2-trans products ( Fig.…”

Palladium-Catalyzed C–S Bond Formation as a Tool for Latent–Active Glycosylation

“…Although carbohydrate chemistry is a subdivision of organic chemistry, palladium has only rarely ventured into this field besides being used as a heterogeneous catalyst for O -debenzylation. We have recently made some use of modern homogeneous palladium catalysis for protecting group manipulations and protecting group-mediated reactivity tuning of glycosyl donors. , In this paper we report on our development of a novel latent–active glycosylation approach using palladium as a central tool and describe how the instalment of a sulfur atom is used to facilitate a subsequent chemoselective step by exploiting the coordinating/chelating ability of a sulfide.…”