Torsional effects on reactivity in glycosyl transfer

Abstract

The net effect of the four substituents on a hexapyranoside is to reduce reactivity at the anomeric centre by a factor of >10⁷ compared with the parent tetrahydropyranyl acetal. The magnitude of the steric contribution to this factor is assessed by measuring the effect of four equatorial methyl groups on the rate of hydrolysis of 4-nitrophenyl tetrahydropyranyl acetal. Though the electronic effects of methyl substituents will be to increase the rate of hydrolysis, the net effect of the four equatorial methyl groups is a 4-fold decrease, evidence for an opposing steric effect estimated at two orders of magnitude. Torsional effects in a glycopyranoside thus contribute a factor of up to 50 towards the total of 10⁷.