Strategies For Asymmetric Synthesis. What Is The Role Of Heterogeneous Catalysis?

Abstract

Enantioselective synthesis is and will remain without any doubt one of the most active area in synthesis. The reason is that many properties of molecules which have potential use as pharmaceutical or agrochemical products or as new materials depend on their absolute configuration. It is thus necessary to develop efficient and economical methods which can be applied to the synthesis of complex molecular systems and meet the following stringent criteria: (a) high efficiency, (b) low cost, (c) friendliness to the environment.

Reactions involving at least one enantiomerically pure reagent or catalyst can lead to an enantiomerically pure product if they occur with total facial selectivity. It is practical to provide the chiral information through a molecular fragment temporarily bonded to one of the reagent or, ideally, to a catalyst (scheme 1).

At present most asymmetric syntheses rely upon the use of a covalently bonded chiral auxiliary. This requires at first the attachment of the auxiliary to one of the reagent by a covalent bond which can be readily cleaved at the end of the sequence. The cleavage step should take place in high yields and without epimerization of the various chiral centers. The chiral auxiliary should be recovered in high yields and without racemisation. Highly successful and practical asymmetric syntheses following this strategy have been described in recent years. Some typical examples are shown in scheme 2.

In recent years one has seen several interesting examples of reactions using Lewis acids bearing enantiomerically pure ligands. These act as catalysts by coordination to a polar substituent (often a carbonyl group) of the electrophilic partner of the reaction and, at the same time, they provide the chiral information. In many cases they must be used in large if not stoechiometric amounts. Thus they cannot be regarded as true catalysts but rather as chiral activators. An illustration of this strategy is shown in scheme 3 [6].