Abstract
Chiral building block syntheses of promising drugs were achieved using two types of catalytic stereoselective cyanosilylations of aldehydes promoted by Lewis acid–Lewis base bifunctional catalysts 1 and 2 as the key steps (diastereoselective cyanosilylation of amino aldehyde and enantioselective cyanosilylation). In the first part of this article, syntheses of chiral building blocks (6) of Atazanavir (3: human immunodeficiency virus (HIV) protease inhibitor) using the bifunctional catalyst 2 are discussed. The reaction of Boc-protected phenylalaninal 21 in the presence of 1 mol% catalyst 2 selectively afforded the anti isomer 22 as the major product (diastereomeric ratio=97 : 3), which was successively converted to the corresponding epoxide 6 in six steps. In the second part, we describe a chiral building block synthesis of β3-adrenergic receptor agonists. The enantioselective cyanosilylation of 3-chlorobenzaldehyde (38) with 9 mol% catalyst 1 gave the chiral cyanohydrin 39, which was converted to β-hydroxyethylamine 40 by reduction. Moreover, the chiral ligand of catalyst 1 could be recovered without column chromatography and reused without decreasing its activity.
