Diastereoselective Catalysis

Abstract

IntroductionA reaction is referred to as stereoselective when a substrate S, which may yield a series of stereoisomer products (P 1 , P 2 , . . . P n ) gives preferentially -or even exclusively -one of these. Today, the preparation of stereoisomeric compounds is generating tremendous academic and industrial interest. Especially, the synthesis of enantiopure chiral compounds is becoming increasingly important in the production of pharmaceuticals, agrochemicals, fragrances, and flavor substances. Among the different methods used to prepare pure enantiomers, asymmetric catalysis plays an important role, particularly hydrogenation. Currently, two types of asymmetric hydrogenation with solid catalysts are utilized, namely enantioselective and diastereoselective synthesis.In enantioselective hydrogenation, one enantiomer of a chiral product is formed preferentially from a prochiral precursor, the stereoselectivity being induced by a chiral catalyst. Immobilization of very selective metal-ligand complexes and modification of active metals by an adsorbed chiral organic molecule (chiral modifier) have been extensively studied [1]. In some cases, high enantioselectivities approaching 98% enantiomeric excess (e.e.) have been obtained with modified supported metal catalysts. The numerous investigations devoted to the understanding of the mechanism have been summarized in several reviews [1][2][3][4][5]. The most effective catalysts are Ni-tartaric acid, Pt-cinchona, Pd-cinchona and, to a lesser extent, Rh-cinchona systems. The field of reaction types is still limited to a narrow range of asymmetric hydrogenations.The other frequently used catalytic strategy for the synthesis of pure enantiomers is based on diastereoselective hydrogenation. This involves the selective formation of one diastereoisomer by creating a new stereogenic center in a chiral molecule. In this approach, the reaction consists of three simple steps. First, a covalent bond between the prochiral substrate and a chiral moiety (chiral auxiliary) is formed. Then, the diastereoselective hydrogenation is performed over various noble metal catalysts, leading stereoselectively to a new chiral center. This step does not require a chiral catalyst, but the stereogenic center in the chiral auxiliary is able to induce the stereoselectivity. The desired molecule can finally be obtained by selective cleavage of the chiral auxiliary from the product which can be recycled.