Diastereoselective hydrogenations of α-alkyl α-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)methylene carbonyl compounds. New route to stereopure α-alkyl α-oxymethyl carbonyl compounds

Abstract

Wittig condensation of the stabilised phosphoranes 9, 10 and 26 with 1-formyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose 11 leads to the vinylogous carbonates 12, 13 and 22. The salts 27–30 and 44, prepared from the corresponding carbonyl compounds, ethyl formate and sodium methoxide, react with acetobromoglucose 21 to give compounds 22–25 and 43.

The vinylogous esters/carbonates 12, 13, 22–25 and 43 undergo stereoselective catalytic hydrogenations under mild conditions to give mainly the dihydro derivatives 14, 15, 31–34 and 16. Although the selectivity for re-face addition is modest (ranging from 85:15 to 67:33), it is possible to isolate the dihydro derivatives 15 and 31–33 in acceptable yields (ranging from 71 to 49%) simply by fractional crystallisation. Acidic hydrolysis of compound 31 provides (αS)-α-hydroxymethyl-γ-butyrolactone 39 in high yield with an ee of ∼96%.

A model to account for the role of the 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl unit in the stereoinduction process is presented.