EXPERIMENTAL AND THEORETICAL EVIDENCE OF THROUGH-SPACE ELECTROSTATIC STABILIZATION OF THE INCIPIENT OXOCARBENIUM ION BY AN AXIALLY ORIENTEDELECTRONEGATIVE SUBSTITUENT DURING GLYCOPYRANOSIDE ACETOLYSIS

The rate of acetolysis of methyl 2,3,6-tri-O-methyl-alpha-D-galacto- a nd -glucopyranosides depends strongly on the electronegativity of the C4 substituent. Thus, of the three derivatives studied (4-methoxy, 4-a cetoxy, and 4-acetamido-4-deoxy derivatives of D-galacto- and D-glucop yranosides), the glycopyranosides bearing the most electronegative C4 substituent (methoxy:group) acetolyze at the fastest rate, whereas tho se having the least electronegative C4 substituent (N-acetamido group) acetolyze at the slowest rate. Furthermore, whereas the influence of the electronegativity of the C4 substituent upon the acetolysis rate i n the D-gluco series is relatively moderate (k(max)/k(min) = 2.9-3.5), this influence is very large in the D-galacto series (k(max)/k(min) = 44.4-58.6). We propose that this observation can only be explained by the existence of an electron donation process from the axially orient ed electronegative substituent at the C4 carbon atom of the galactopyr anoside ring to the forming oxocarbenium ion. Such a through-space phe nomenon cannot: occur in the glucopyranoside series where the C4 carbo n substituent is oriented equatorially. Ab initio calculations of mode l molecules fully support the above conclusions.