Stereoelectronic control of the hydrolysis of a conformationally locked acetal

Abstract

The hydrolysis of the nitrophenyltetrahydropyranyl acetal (3e; Y = H), with leaving group fixed equatorial by the trans-ring junction, is substantially slower than expected for a comparable conformationally flexible acetal. It is also slower than the hydrolysis of the axial isomer, by a factor of 60 in acid, but only 2 for the spontaneous reaction. It is suggested that both reactions of (3e) are slow because there is a stereoelectronic barrier to the departure of an equatorial leaving group, not readily overcome in a system where the conformation at the acetal centre is fixed by a trans-ring junction. The spontaneous hydrolysis of (3a) appears to be slow for a different reason: rapid internal return from the initial product of C–O cleavage enforces a change in rate-determining step, to hydration of the oxocarbonium ion, as shown by the solvent deuterium isotope effect for this reaction.