THE MECHANISM OF THE ANOMERIZATION OF THE TETRA-O-ACETYL-D-GLUCOPYRANOSYL CHLORIDES

Abstract

The anomerization of the tetra-0-acetyl-D-glucopyranosyl chlorides in acetonitrile is first order in chloride ion. Experiments with 3GCl-labelled chloride ion showed the reaction t o involve nucleophilic attack ( S N~) by chloride ion a t the anomeric center. The reaction is accompanied by a faster dissociation of the p-anomer (I) to the l,2-acetoxonium ion. Although the rate of anomerization was slightly accelerated by addition of benzene, the ionic reaction was strongly suppressed. Bromide ion was less effective than chloride ion in catalyzing the reaction and iodide ion was least effective. Reaction of tetra-0-acetyl-cr-~-glucop~ranos~l bromide with tetraethylammonium chloride in acetonitrile rapidly gave I in high yield. The anomeric effect for chlorine appears to be about 2 Ircal/mole.

MECHANISMS FOR THE REACTIONS OF THE ANOMERIC TETRA-O-ACETYL-D-GLUCOPYRANOSYL BROMIDES WITH PYRIDINE AND 2-PYRIDONE

“…I t could be speculated t h a t the ion X I is closer t o the 1C-than the Cl-conformation and provides a-pyridinium glucoside (111) for this reason. However i t is well established that the 1,2-acetoxonium ion is formed in the anomerization of both penta-O-acetyl-~-~-g~ucopyranose (14) and tetra-O-acetyl-/3-~-glucopyranosyl chloride (4) and that the ion does not offer a facile route t o the formation of the a-anorners. For this reason, i t seems best to assume that the a-glucoside (111) is formed by a rearrangement of a pyridine -acetoxonium ion complex.…”

Some recent developments in stereoelectronic theory. Reevaluations of ALPH and the reverse anomeric effect

“…Intriguingly, in fact, the apparent success of the in situ anomerisation procedure (mentioned above), 9,34,35 appears to indicate that this is probably the major pathway, thus posing a major challenge to ALPH! On the other hand, the studies on the restricted models 3 and 4 (cf.…”

Strategies for the Chemical Synthesis of Glycoconjugates

“…P-Glucotype structures are readily accesible via neighboring group participation. However, the formation of a-gluco-type structures depends strongly on thermodynamic control or on SN2-type reactions when the "in situ-anomerization" procedure of axial to equatorial glycosyl halides (introduced by Lemieux and Haymi, 1965) is employed. Obviously, the formation of P-manno-type structures, most commonly found in the branching position of N-glycoproteins, is supported neither by the thermodynamic anomeric effect nor by neighboring group participation.…”