Synthesis of 3,5-Anhydro-2-deoxy-1,4-glyconolactones by Palladium(II)-Catalyzed, Regioselective Oxycarbonylation of C₅- and C₆-Enitols. ω-Homologation of Aldoses to Produce Intermediates for<i>C</i>-Glycoside/<i>C</i>-Nucleoside Synthesis

Abstract

The palladium(II)-catalyzed oxycarbonylation, known with alkenols and alkenediols, is studied with optically active 4-pentenitols (-triols) 1, 7 and 5-hexenitols (-tetrols) 12, 15, 18. Efficient routes for the substrates are provided, mostly from carbohydrate precursors. In all cases, bicyclic 3,6-anhydro-2-deoxy-1, 4-glyconolactones, versatile intermediates of C-glycosidic structure, are isolated with high selectivity and in good yield (53-77%). Several minor products (4-14% of regio-/diastereoisomers) from two competing pathways are observed and identified. The oxycarbonylation of alkenitols thus completes a novel sequence that transforms aldoses into homologous anhydro-glyconolactones, by C1-elongation at the terminal site. In the key step, the 3,4-threo arrangement is produced, from each of the four diastereomeric alkenitols studied (of the 6 cases available in the C5 and C6 series). The stereochemical protocol is summarized, e.g., by the transition D-gluco (aldose) → D-xylo (hexenitol, 15) → L-ido (anhydro-deoxyheptenolactone 26), as demonstrated.