Diastereoselective Synthesis of Axially Chiral Xylose-Derived 1,3-Disubstituted Alkoxyallenes: Scope, Structure, and Mechanism

Abstract

The deprotonation of differently substituted propargyl xylosides with s-BuLi/TMEDA followed by protonation with t-butanol at-115 °C provided a range of new axially chiral 1,3-disubstituted alkoxyallenes in a diastereoselective way. Numerous reaction parameters such as solvent, temperature or protonating agent were examined as well as protecting groups on the xyloside moiety and the influence of the substituents on the alkyne part. The configuration of the main diastereoisomer of 3-methyl-1-xyloside-allene was determined for the first time by single crystal X-ray diffraction analysis and nOe NMR experiments. Furthermore, DFT calculations on the propargyl/allenyl lithium intermediates formed in the course of the deprotonation reaction provided new structural insights of these complexes. The subsequent protonation process with alcohols was investigated by theoretical surface exploration, revealing the importance of the approach of the alcohol towards the lithium compounds on the reaction outcome. Results and Discussion Synthesis of various substituted propargyl xylosides 3a-f from 1. Propargyl β-D-xylopyranoside 1 can be obtained either by a classical three-step chemical sequence from D-xylose or through an enzymatic transglycosylation process directly from beechwood xylans and propargyl alcohol. 6c,11 The fully TBS protected propargyl xyloside 2 was readily prepared in up to 91 % yield from 1 by reaction with t-butyldimethylsilyl chloride (TBS-Cl) in presence of imidazole and a catalytic amount of DMAP (Scheme 3) after heating at 80 °C for 6 days. 5b Lower temperatures or shorter reaction times led to the formation of product mixtures containing diand triprotected xylosides. Introduction of substituents on the alkyne was carried out via deprotonation and nucleophilic substitution for alkyl or silyl groups leading to 3a,b or Pd-catalyzed Sonogashira 12 coupling for aryl groups providing 3c-e in good to excellent yields. The t-butyl substituted compound 3f could not be obtained by these pathways, but via a 4-step procedure from D-xylose (see S1 in SI). Scheme 3. Synthesis of various propargyl xylosides 2 and 3a-e.

New Water‐Soluble Au(III) Complexes with Xyloside‐Based Ligands: Synthesis, Structural Characterization, Solution Studies and Catalytic Evaluation

“…Materials and methods : Ethyl 2‐[(2,3,4‐tri‐ O ‐acetyl‐ β ‐ d ‐xylopyranosyl)oxy]acetate ( A) was synthesized as previously described in the literature [14d] . All other reagents were commercially available and used as received.…”

“…As part of our work dedicated to the sustainable development strategy, we have developed several research projects related to this topic over the past fifteen years using chemical routes for various applications [14a] such as the stabilization of gold nanoparticles with glycodendrimers, [14b] enzymatic inhibition, [14c] in organic synthesis with the diastereoselective synthesis of allenes [14d] or enzymatic routes [14e] for applications in surfactants, [14f] in ionic liquids [14g] and in the activation of the biosynthesis of glycosaminoglycans [14h] …”

A Xyloside‐Based Ligand to Stabilize Gold Nanoparticles: Preparation and Application

“…The use of xylose to stabilize AuNPs is therefore in line with a sustainable development approach. As far as we are concerned, [13] several research projects have been developed over the last fifteen years with different chemical or enzymatic transformation routes of d ‐xylose for applications in different fields such as the preparation of water‐soluble Au(III) complexes with xyloside‐based ligands, [13b] the stabilization of gold or palladium nanoparticles with glycodendrimers, [11a,13c] organic synthesis, [13d] surfactants, [13e] ionic liquids [13f] or on more biological aspects such as enzymatic inhibition [13h] or the activation of glycosaminoglycan biosynthesis [13i] …”