Efficient intramolecular general acid catalysis of enol ether hydrolysis. Hydrogen-bonding stabilisation of the transition state for proton transfer to carbon

Abstract

The intrinsically low efficiency of intramolecular general acid–base catalysis is enhanced when the proton transfer generates a strong intramolecular hydrogen bond. This principle is shown to apply to proton transfer to carbon: the carboxy groups of methyl vinyl ethers 3E and 3Z derived from 2-carboxyphenylacetaldehyde act as general acids to catalyse the hydrolysis of the neighbouring enol ether groups with effective molarities (EM) of about 300 and 2000 M, respectively. The solvent deuterium isotope effects confirm that the usual mechanism for enol ether hydrolysis is operative. In this system the oxocarbocation intermediate is trapped by the neighbouring carboxylate group to give the acylal 6, rather than the formal product of hydrolysis.