Some rearrangements of 2-deoxy-3,4,6-tri-O-methyl-2-methylamino-D-glucose and related compounds in basic solution; a novel base-promoted N→O migration of a phosphonate ester

Abstract

Treatment of 2-deoxy-2-methylamino-3,4,6-tri-O-methyl-D-glucose (1) with sodium alkoxides affords 1-methyl-5-methoxymethylpyrrole-2-carbaldehyde (2) presumably by a series of elimination reactions and keto–enol equilibrations which precede ring closure and elimination of water. Substitution of nitrogen in (1) to give e.g. 2-N-[(R)-O-ethyl (phenyl)phosphoryl]-2-deoxy-2-methylamino-3,4,6-tri-O-methyl-D-glucose (8) interferes with the elimination sequence at an early stage so that when (8) is treated with sodium ethoxide a novel N→O migration of the phosphonate ester group occurs in a rapid reaction sequence which results in the conversion of (8) into 3-deoxy-2N-methyl-4,6-di-O-methyl-α,β-D-erythro-hexofuran-2-ulosylamine 1,1-diethyl acetal in high yield. The N→O migrations in this type of reaction involve P–N bond cleavage with retention of configuration at phosphorus, an unusual if not unique occurrence for reactions under basic conditions.