Novel Lewis acid catalysis in organic synthesis

Cationic zirconocene or hafnocene complexes serve as a novel class of Lewis acid with unique reactivities, which are to be exploited in organic synthesis. Four categories of reactivities are discussed, that is, (A) C-F bond activation/cleavage, (B) Coordinative activation of ether linkages, (C) Carbonyl activation, and (D) C-0 bond cleavage via zirconocene alkoxide. Introduction Lewis acid-promoted reactions are becoming of increasing importance in current organic synthesis (ref. 1 ) . A general idea for such reactions is shown in Scheme 1. Initial coordination of a Lewis acid occurs to the basic site of the substrate. When the activation level reached high enough, the ionization occurs to generate a cationic species, which is reverted to the starting material or trapped by a nucleophile to give the product. The Lewis acid plays the key role to determine the overall reaction path by controlling the generation and trapping of the cationic species. If the substrate has many basic functionalities, specificity is required for this acid-base interaction in that one particular functionality is to be activated but not the others. The Lewis acid decides also the nature of the cationic species generated, an ion pair or a loosely bound covalent species or somewhere in-between. n Activation CI L I Reversion Scheme 1 In this context, we have recently been finding that the cationic zirconocene or hafnocene complexes behave as a new class of Lewis acid with unique reactivities, which would be useful in organic synthesis. Four categories (A-D) of the reactivities of such cationic complexes are discussed. A C-F bond Activarion of c Curbony1 D C-0 Bond Clw wge Ether. Linknge Actiwtion Clenwigr Results and Discussion (A) The C-F bond activatiodcleavage Some years ago. we found that the combination of hafnocene dichloride and silver perchlorate acts as a powerful activator of glycosyl fluoride (ref. 2 ) . Scheme 2 shows our reasoning for the origin of the