Reagent‐Controlled α‐Selective Dehydrative Glycosylation of 2,6‐Dideoxy‐ and 2,3,6‐Trideoxy Sugars

Abstract

We have found that activating either 2,3-bis(2,3,4-trimethoxyphenyl)cyclopropenone or 2,3-bis(2,3,4-trimethoxyphenyl)cyclopropene-1-thione with oxalyl bromide results in the formation of a species that promotes the glycosylation between 2,6-dideoxy-sugar hemiacetals and glycosyl acceptors in good yield and high α-selectivity. Both reactions are mild and tolerate a number of sensitive functional groups including highly acid-labile 2,3,6-trideoxy-sugar linkages.

An Improved Approach to the Direct Construction of 2‐Deoxy‐β‐Linked Sugars: Applications to Oligosaccharide Synthesis

“…As part of an ongoing program to develop a toolkit for selective reagent-controlled methods for 2-deoxy-sugar synthesis, [12] we have studied the utility of glycosyl sulfonates for the stereospecific construction of β-linkage targets. [13] Specifically, we have found that by matching the sulfonate leaving group ability with the 2-deoxy sugars reactivity, it is possible to generate species that react selectively through an S N 2-like manifold.…”

“…[12a] To assess the utility of the reagent for glycoside construction, we carried out side-by-side glycosylations comparing p -toluenesulfonic anhydride (Ts 2 O) and TsCl in the reaction between donor 1 and p -methoxyphenol. Pleasingly, both reagents provided the β-glycoside 2 as a single diastereomer in 54 % and 56 % yield, respectively (Table 1).…”

“…Activating 6 in [D 8 ]THF with TsCl at −78 °C, led to the formation of a species with an anomeric proton signal at 6.0 ppm indicative of an α-glycosyl sulfonate [12a,e,13a,18] (see Supporting Information, Section S5.1). The 1 H– 13 C heteronuclear single-quantum correlation (HSQC) NMR spectrum correlates the 1 H NMR spectrum singlet at 6.0 ppm to a 13 C NMR signal at 101.5 ppm, which is again consistent with an anomeric sulfonate.…”

“…This supports a mechanism where the donor is converted into an α-glycosyl sulfonate intermediate, which reacts predominantly through an S N 2-like manifold. [12e] …”

Mild Method for 2-Naphthylmethyl Ether Protecting Group Removal Using a Combination of 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and β-Pinene

“…12,13 Owing to the highly labile nature of deoxy-sugars, we had to limit our studies to reactions that did not require the use of strong acid. To this end, we studied the reaction of disaccharide 1 with DDQ in the presence of CH 2 Cl 2 and water under conditions described by Danishefsky and co-workers.…”