INTRAMOLECULAR STRATEGIES AND STEREOELECTRONIC EFFECTS - GLYCOSIDES HYDROLYSIS REVISITED

It has been generally accepted that stereoelectronic effects play an important role in hydrolytic processes. However, the stereoelectronic theory has been criticized because the relative rates of glycosides hydrolysis could not be readily explained. Alternative mechanisms based on a synperiplanar pathway or on the principle of least motion have been proposed. A brief survey of the evidence provided by us and others which support stereoelectronic principles is presented. More recent works on the kinetically controlled spiro acetalization of hydroxy enol ethers show that spiroacetal formation takes place via an early transition state while following the antiperiplanar pathway. This approach corresponds closely to the Burgi-Dunitz angle of attack of a nucleophile on a pi-system. As a result, transition states having a geometry which corresponds to the beginning of a chair form are preferred over those corresponding to a boat form. The general mechanism of reactions occurring at the anomeric center in alpha and beta-glycosides, including kinetic data for hydrolysis can be rationalized on that basis. Proposed alternative pathways are also examined.