The design and synthesis of novel anomeric hydroperoxides: influence of the carbohydrate residue in the enantioselective epoxidation of quinones

We present a study of the base (DBU)-catalysed epoxidation of a number of important naturally occurring quinones using a series of pyranose-derived anomeric hydroperoxides. The absolute (viz. D or L) stereochemistry of the carbohydrate, electronic nature of the 6-substituent and ring substitution are all important variables. both for the formation of the hydroperoxide and its reactivity. Reactions studied were the epoxidation of a precursor of the natural antibiotic. alisamycin and a series of naphthoquinones related to Vitamin K. In the best case, an ee of 82% was obtained; either product enantiomer is accesssible according to the absolute stereochemistry of the carbohydrate. Finally, a molecular modelling study of the reaction is reported, concluding chat the reactions are under kinetic control and that the observed ees cannot be explained by considering transition states, that involve only the quinone and peroxide anion. It seems likely that the DBU molecule may., play a key role in the transition state. (C) 2004 Elsevier Ltd. All rights reserved.