Amine-catalyzed asymmetric epoxidation of α,β-unsaturated aldehydes

Abstract

The direct organocatalytic enantioselective epoxidation of α,β-unsaturated aldehydes with different peroxides is presented. Proline, chiral pyrrolidine derivatives, and amino acid-derived imidazolidinones catalyze the asymmetric epoxidation of α,β-unsaturated aldehydes. In particular, protected commercially available α,α-diphenyl- and α,α-di(β-naphthyl)-2-prolinols catalyze the asymmetric epoxidation reactions of α,β-unsaturated aldehydes with high diastereo- and enantioselectivities to furnish the corresponding 2-epoxy aldehydes in high yield with up to 97:3 dr and 98% ee. The use of non-toxic catalysts, water and hydrogen peroxide, urea hydroperoxide or sodium percarbonate as the oxygen sources could make this reaction environmentally benign. In addition, one-pot direct organocatalytic asymmetric tandem epoxidation-Wittig reactions are described. The reactions were highly diastereo- and enantioselective and provide a rapid access to 2,4-diepoxy aldehydes. Moreover, a highly stereoselective one-pot organocatalytic asymmetric cascade epoxidation-Mannich reaction, which proceeds via the combination of iminium and enamine activation, is presented. The mechanism and stereochemistry of the amino acid- and chiral pyrrolidine-catalyzed direct asymmetric epoxidation of α,β-unsaturated aldehydes are also discussed. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.