Glycoside hydrolysis electrophiles

Electrophilic catalysis of the departure of halogens in the century-old Koenigs-Knorr reaction is implicit in the use of heavy metal bases such as silver oxide and mercuric cyanide, but the first demonstration of electrophilic catalysis in water (in the hydrolysis of the p-glucoside of 8-hydroxyquinoline by first-row transition metals (Cu Np > C")) was by Clark and Hay in 1973. The observations were expanded to the more conveniently followed (because more labile) benzaldehyde methylacetals or tetrahydropyranyl derivatives of 8-hydroxyquinoline, whose hydrolysis is now known to give solvent-equilibrated oxocarbenium ions (Figure 3.19). Surprisingly, however, the observation of electrophilic catalysis of glycoside hydrolysis itself was not picked up by paper... 

In an extension beyond hetaryl onium salt promoted hemiacetal activation, Ishido and coworkers have reported the carbodiimide activation of hemiacetals [141]. In the method (Scheme 3.13), the hemiacetal donor 1 is treated with a carbodiimide electrophile 83 and copper(I) chloride to provide glycosyl isourea intermediate 85. Highly susceptible to hydrolysis, the isourea 85 was not isolated but could be detected by 13C NMR and IR spectroscopy [142,143], Accordingly, the reaction between intermediate 85 and the glycosyl acceptor (NuH) provides glycoside product 3, along with urea by-product 84. 

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