Regio- and stereo-selectivity issues in radical brominations of allylic units of vinylogous esters/carbonates bearing the 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl auxiliary and in nucleophilic displacements of the derived allylic bromides

Abstract

Under radical conditions, N-bromosuccinimide effects bromination of the methyl group of the 1-oxyallyl unit of (E)-3-methyl-4-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)but-3-en-2-one 1a, (E)-2-methyl-1-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)pent-1-en-3-one 1b and methyl/ethyl (E)-2-methyl-3-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)prop-2-enoate 1c/1d to give the bromoethyl derivatives 14a–14d.

Displacement of the bromine atom of compounds 14a–c occurs without allylic rearrangement (in Me₂CO under reflux and/or in MeCN at ambient temperature) with sodium azide (to give the azidomethyl derivatives 15a–c), potassium O-ethyl dithiocarbonate [to give the ethoxy(thiocarbonyl)thiomethyl derivatives 16a–c] and with potassium thiocyanate (to give the thiocyanatomethyl derivatives 17a–c). Silver(I) thiocyanate in acetonitrile also effects the 14a → 17a conversion.

Compounds 14a, 14b and 14d react with sodium acetate in boiling acetonitrile to give largely the rearranged acetates 19a/20a, 19b/20b and 19d/20d with a moderate degree of stereoselection under kinetically controlled conditions. However, equilibration slowly occurs under the reaction conditions (requiring the presence of NaOAc) to give mainly the unrearranged acetates 18a, 18b and 18d. With silver(I) acetate in acetonitrile, the bromides 14a and 14d are transformed into the rearranged acetates 19a/20a and 19d/20d with a good degree of stereoselection and without appreciable equilibration. The reaction of the bromide 14a with silver(I) oxide and acetic acid parallels that observed with sodium acetate, the equilibration of the acetates 18a, 19a and 20a being induced by acetic acid.

The bromide 14a reacts with alcohols at ambient temperature in the presence of silver(I) oxide to give, in kinetically controlled reactions, mixtures of rearranged alkoxy derivatives of types 24/25 and unrearranged alkoxy derivatives of type 23. Although the former products predominate, their proportion in the mixture declines as the size of the alcohol increases. Similar results are observed for the bromides 14b and 14d.

The ambident reactivity of allylic bromides of type 14 towards nucleophiles is consistent with the principle of hard and soft acids and bases.

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