Conformational effects in 2‐deoxyglucopyranos‐1‐yl radicals

Abstract

Key Words: ESR spectroscopy / Conformational analysis / Carbohydrate radicals / Anomeric effect 2-Unsubstituted and 2-substituted (fluoro, tosylamino, n-propyl) 3,4,6-tri-O-acetyl-2-deoxypyranosyl radicals are obtained by reaction of the corresponding pyranosyl bromides or phenyiselenides with photolyticaily generated trimethyltin radicals in benzene solution. Analysis of the ESR hyperfine splittings reveals that the 2-deoxy-2-fluoroglucopyranosyl radical exists in a boat-like conformation at room temperature, whereas the others retain the 4C1 chair conformation of the starting material. The observed conformational effects are 5%-plained by a "quasi-homo-anomeric" frontier orbital interaction of the n, lone pair of the ring oxygen atom with the (r* MO of the p-C -0 bond, in which the singly occupied p orbital at C-1 acts as a mediator for this 1,3-anomeric interaction.Recently, it has been demonstrated that radical-induced intermolecular C-C coupling reactions can serve as a useful tool in synthetic carbohydrate chemistry*). 0-protected pyranosyl compounds in which the radical center is generated at different positions of the carbon skeleton sometimes show a markedly enhanced diastereoselective preference in C -C bond formation. In the course of our ESR-spectroscopic investigations 3A of the intermediate carbohydrate radicals we have observed that in non-aqueous solution x-type C-1 pyranosyl radicals, derived from all-equatorially substituted (glucosyl-type) precursors, transform into a boat-like conformation C instead of retaining the sterically more favored 4C1 chair conformation A of the starting material. The primary radical B can be observed only in a low-temperature matrix5). From the ESR data we have deduced a twisted B2,5 boat conf~rmation~,~' to be the most populated equilibrium conformation of the C-1 glucosyl radicals.Our original explanation for the conformational change B + C by frontier molecular orbital arguments has been modified r 1 recently ' ! We propose a so-called "quasi-homo-anomeric" stabilization effect to be operative when the p -C -0 bond is in a parallel orientation with the singly occupied p orbital (see Discussion). Our interpretation is strongly supported by the fact that in 2-mannopyranosyl-type systems E, where the p-C-0 bond is already in the axial position, no conformational change can bc observed 3!Regarding the quasi-homo-anomeric effect in C-1 pyranosy1 radicals as a special case of the general anomeric effect'), we expect it to be operative also in pyranosyl radicals carrying substituents at C-2 of equal or higher electronegativity than oxygen and viceIn the present study we report on the conformation of C-1 glucopyranosyl radicals where the P-oxygen substituent is replaced by hydrogen, fluorine, n-propyl, or tosylamino. Results ESR Measurements A BThe pyranosyl radicals (1 R -8R) have been generated in benzene solution in the cavity of the ESR spectrometer by reaction of the corresponding 1-bromo-or l-phenylselenosubstituted compounds (1 -8) with trimethyltin radicals, produ...

Ketone Isosteres of 2-N-Acetamidosugars as Substrates for Metabolic Cell Surface Engineering

“…Keck radical coupling of methallyltributyltin with 2-iodo glucose analogue 1 or 2-iodo galactose analogue 2 afforded 2-methallylpyranosides ( 3 and 4 ) as the major products (6:1 and 7:1 equatorial:axial methallylation, respectively) (Scheme ). The predominance of the equatorial over the axial isomer is in accordance with diastereoselectivities previously reported by Giese and co-workers . Ozonolysis of compounds 3 and 4 , followed by reduction with dimethyl sulfide (DMS) and HPLC purification, gave the peracetylated 2-ketosugars 5 and 6 .…”

Ring-Closing Olefin Metathesis of 3,3′-(D-Glycopyranosylidene)bis(1-propene) Compounds as a Route to Anomeric Spiro Sugars

“…Sect.). It was probably formed only in trace amounts, in keeping with the 9:1 and 6:4 diastereoselectivities in favor of the D ‐ gluco ‐branched sugars35 found for allyltributyltin‐mediated allylation of 1,3,4,6‐tetra‐ O ‐acetyl‐2‐bromo‐2‐deoxy‐β‐ D ‐glucopyranose (43% total yield),35a and methyl 3,4,6‐tri‐ O ‐acetyl‐2‐deoxy‐α‐ D ‐ arabino ‐hexopyran‐2‐yloside radical,35b respectively. To the best of our knowledge,24a formation of 15 is the first example of acetoxy group migration towards a substituted D ‐glucopyranos‐1‐yl radical.…”

Probing the Influence of Protecting Groups on the Anomeric Equilibrium in Sialic Acid Glycosides with the Persistent Radical Effect

“…Thus, ESR studies of the tri-O-acetyl-2-deoxy-1glucosyl radical 19 show it to adopt a chair conformation with an out of plane bend of ∼6°for the anomeric carbon consistent with a radical that is 90% sp 2 hybridized. 118,119 The methoxycarbonylmethyl radical 20 is a planar π-radical with extensive delocalization onto the carboxyl oxygen and a barrier to rotation about the CH 2 −CO 2 Me bond of ∼11 kcal mol −1 , 120 and the methoxy(methoxycarbonyl)methyl radical 21 displays ESR parameters that closely mirror those of 20, including the hyperfine splitting a Hδ indicative of coupling to the ester methyl hydrogens, which is diagnostic of extensive delocalization. 121 Finally, the close model radicals 22 and 23 also show ESR spectral parameters consistent with those for 20, including hyperfine splitting by the ester methyl hydrogens and two distinct rotamers about the C5−CO 2 Me bond.…”