Asymmetric reduction of CC and CO bonds: stereochemical approach

Abstract

Simple stereochemical rules have been found that establish a relationship between product configuration and catalyst or reactant configuration for the two most effective and extensively studied asymmetric reactions, viz., asymmetric hydrogenation of dehydroacylamino acids in the presence of chiral rhodium-phosphine complexes and asymmetric reduction of ketones with chiral hydrides. As regards the first reaction, an analysis of available X-ray data as well as of molecular models of catalytic complexes made it possible to suggest a stereochemical rule that correlates the configuration of phosphorus atoms in the chelate ring of a complex with the product configuration. This rule is also valid for non-symmetric chelates (in terms of dentate groups), such as the rhodium complex with PheNOP [PhCH 2CH(CH 3NPPh 2)CH 2OPPh 2] synthesized and investigated by the authors. The observed effect of hydrogen pressure, substrate concentration, temperature and solvents used on the optical yield of acetamidocinnamic acid hydrogenation in the presence of this complex points to the primary formation of the hydride intermediate. In the absence of the substrate, it was detected by NMR and IR spectroscopy under the reaction conditions. For the second reaction, the rule of quadrants was suggested, which links the chiral hydride structure and the product configuration in acetophenone reduction with hydrides obtained by incomplete decomposition of LiAlH 4 or NaBH 4 with chiral alcohols, amines or acids. In the case of the chiral hydride prepared by the incomplete decomposition of NaBH 4 with diisopropylidenefuranose and an organic acid, the use of this rule permitted prediction of a favourable effect of increased acid radical bulk on optical purity, the effect in question being corroborated experimentally.