Metal perchlorates as Lewis acids: a powerful and versatile tool in organic synthesis

Metal perchlorates are compounds of great chemical interest since they own some unique properties, such as high electronegativity and relatively low charge density, poor complexing ability, high solubility in various organic solvents and kinetic stability under mild conditions. Besides forming polar media when dissolved in solvents, metal perchlorates recently found large employment as Lewis acid promoters in various organic transformations, both in developing new protocols for known and largely used reactions, both in promoting new kinds of reactivity. In this chapter we review our studies and results on the use of metal perchlorates as Lewis acids in various organic reactions under mild reaction conditions, compared with the most important ones appeared in the literature on the same topic. For instance, lithium perchlorate, the most used perchlorate in the past years especially as co-catalyst, proved to be a very efficient promoter for the Friedel Craft acylation of aromatic substrates. On the other hand, small amounts of anhydrous magnesium perchlorate can promote the formation of esters, carbonates and t-butyl ethers from alcohols, the Knoevenagel condensation between –diketones and aldehydes, and multicomponent domino reactions to form functionalized 1,4-tetrahydropyridines. In some cases, such as in the esterification of alcohols with anhydrides and in the conversion of –keto derivatives to the corresponding –enamino derivatives, zinc perchlorate hexahydrate proved to be much more efficient than other Lewis acids. Notably, it is also able to catalyze the Fischer condensation of equimolecular amounts of acids and alcohols. Finally it is important to underline that under mild reaction conditions, i.e. relatively low temperatures and not highly acidic reaction media, metal perchlorates are safe chemical reagents.