Lewis Acid‐Catalysed Anomerisation and Rearrangement of Alkyl D‐Glycopyranosides During Acetalisation with Methyl Pyruvate: How to Utilise it for the Preparation of 1‐(Carboxyethylidene)glycopyranosyl Donors

Abstract

The preparation of 4,6‐O‐(1‐methoxycarbonylethylidene)‐D‐glycopyranosides 5 starting from 2,3‐di‐O‐benzoyl‐D‐glycopyranosides 1 and their 4,6‐bis‐O‐trimethylsilyl ethers 2 using methyl 2,2‐bis(phenylthio)propionate (4) and methyl pyruvate (3), respectively, under Lewis acid catalysis conditions is described. In the D‐gluco series anomerisation of alkyl β‐D‐glucopyranosides is observed as a side reaction, giving complex mixtures and low yields of the title compounds whereas alkyl‐α‐D‐glucopyranosides and alkyl or phenyl 1‐thio‐β‐D‐glucopyranosides react without anomerisation. The reactions are accompanied by isomerisation of the initially formed diastereomer (R)‐5 having an equatorial methoxycarbonyl group to the thermodynamically favoured diastereomer (S)‐5 having the methoxycarbonyl group in an axial position. In the D‐galacto series similar side reactions are observed accompanied by rearrangement to furanosides 9 of alkyl and phenyl β‐D‐galactopyranosides. The results are used for efficient syntheses of two protected disaccharides 8 and 11 representing structural fragments of the polysaccharide repeating units of Mycobacteria and Rhizobia via pyruvate acetal‐containing glucosyl and galactosyl donors 7 and 10.

4,6-O-[1-Cyano-2-(2-iodophenyl)ethylidene] Acetals. Improved Second-Generation Acetals for the Stereoselective Formation of β-d-Mannopyranosides and Regioselective Reductive Radical Fragmentation to β-d-Rhamnopyranosides. Scope and Limitations

“…This galactopyranoside to furanoside rearrangement is readily apparent from the downfield shifts of the anomeric hydrogen and carbon in the 1 H and 13 C NMR spectra, respectively, as well as from the collapse of the anomeric proton signal to a broad singlet in the furanose, as discussed by Ziegler …”

“…Scrutiny of the spectral data for 65 − 69 revealed these structures to have been misassigned in the original publication, and we now revise these structures, along with their precursors described in the original Supporting Information, to the galactofuranoside substrates 70 and 71 and the 5- and 6-deoxygalactofuranoside products 72 , 73 , and 74 . The error in assignment of these structures arose because of a methyl galactopyranoside to methyl galactofuranoside rearrangement , that had gone undetected during the Lewis acid (TMSOTf) mediated acetalization of 75 , which it is now clear gave the furanosides 76 and not the pyranosides 77 . The sequence employed originally in the intended synthesis of 65 and 66 was predicated on the need to introduce the acetal and complete the subsequent transesterification step to the thiol ester before introduction of any ester protecting groups.…”

Cyclic Phosphate-Linked Oligosaccharides: Synthesis and Conformational Behavior of Novel Cyclic Oligosaccharide Analogues

“…Commercially available phenyl-β- d -glucopyranoside 4 was first converted into 4,6- O -benzylidene derivative 5 by a reaction with benzaldehyde dimethylacetal in the presence of catalytic amounts of p -toluenesulfonic acid (PTSA) and then treated with an excess of benzoyl chloride in pyridine to give 6 . The successive addition of I 2 in CH 3 OH in the presence of triethylsilane (Et 3 SiH) allowed the selective removal of the benzylidene protecting group, and the primary hydroxyl group of diol 7 was then protected by a reaction with 4,4'-dimethoxytriphenylmethylchloride (DMTCl) in pyridine. Compound 8 was subsequently phosphitylated by addition of 2-cyanoethyl- N , N -diisopropyl-chlorophosphoramidite and diisopropylethylamine (DIEA), leading to the desired 9 .…”

Lewis acid promoted anomerisation of alkyl O- and S-xylo-, arabino- and fucopyranosides

“…10,11 It was proposed in the latter case that the C-5 carbonyl group facilitates chelation by Lewis acids such as TiCl4 or SnCl4 and subsequent endocyclic cleavage (Scheme 1). 12 This chelation renders anomerisation of the uronic acids more efficient than for benzoylated gluco-and galactopyranosides. 12 Chelation, however, is not ruled out for (acylated) gluco-and galactopyranosides given they contain oxygen atoms at C-6 that can potentially chelate.…”

“…12 This chelation renders anomerisation of the uronic acids more efficient than for benzoylated gluco-and galactopyranosides. 12 Chelation, however, is not ruled out for (acylated) gluco-and galactopyranosides given they contain oxygen atoms at C-6 that can potentially chelate. Anomerisation can also proceed through an exocyclic cleavage pathway (Scheme 1).…”