On the Role of Neighboring Group Participation and Ortho Esters in β-Xylosylation:  ¹³C NMR Observation of a Bridging 2-Phenyl-1,3-dioxalenium Ion

Abstract

The role of ortho esters in the formation of 2,3,4-tri-O-benzoyl-β-xylopyranosides from various donor/promoter pairs has been investigated. It is concluded that for the activation of sulfoxides with Tf2O, thioglycosides with PhSOTf, and bromides with AgOTf the anomeric configuration of the donor is of no consequence on the outcome of the reaction. In all methods studied, the presence or absence of a non-nucleophilic, hindered base is of crucial importance with ortho esters only being discernible in its presence. S-Phenyl 2,3,4-tri-O-benzoyl-1-deoxy-1-thia-β-d-xylopyranoside was synthesized enriched with 13C at each of the three carbonyl carbons. Activation of this thioglycoside with PhSOTf in CD2Cl2 at −78 °C with or without the base permits, for the first time, the observation by 13C NMR spectroscopy of a bridging dioxalenium ion as an intermediate in a neighboring group directed glycosylation. Quenching of this cation in the presence of the base leads to the ortho ester, whereas in the absence of the base the glycosides are the only products detected.

Installation of Electron-Donating Protective Groups, a Strategy for Glycosylating Unreactive Thioglycosyl Acceptors using the Preactivation-Based Glycosylation Method

“…These correlations strongly suggest the bridging dioxalenium ion 41 formed through participation by the neighboring O-2 benzoyl group. The chemical shift of 180.8 ppm for the bridging carbon in 41 was similar to the value of 180.3 ppm observed for the dioxalenium ion 42 formed from xyloside 43 55. The HSQC spectrum of 41 indicated that the anomeric carbon was also downfield shifted to 114.2 ppm (Figure S3).…”

Direct Experimental Evidence for the High Chemical Reactivity of α‐ and β‐Xylopyranosides Adopting a 2,5B Conformation in Glycosyl Transfer

“…Anomeric substituent ) that was 226-fold faster than the conformationally flexible thioxyloside 30 [36] (k = 8.4 10 À4 s À1 ) at performing glycosylation. In this case, release of steric strain can be excluded as an explanation for the observed effect.…”

Semi‐synthesis of Several Stigmasterol Saponins

“…The use of 2-O-benzoyl-glycosyl donors can commonly produce a unique 1,2-trans-glycosidic bond due to the participation of a neighboring group. 10 The glycosyl donors involved in the synthesis are shown in Scheme 2. Glycosyl trichloroacetimidates 1a-6a were readily prepared in good yields from the corresponding 1-OH sugars.…”