Asymmetric Copper(I)-Catalyzed Henry Reaction with an Aminoindanol-Derived Bisoxazolidine Ligand

Abstract

Bisoxazolidine 1 is an effective ligand in the Me2Zn-promoted and the Cu(I)-catalyzed Henry reaction. While a wide range of nitroaldol products are obtained in high yields and ee's in both cases, the replacement of dimethylzinc with copper(I) acetate results in a complete reversal of the sense of asymmetric induction. The Cu(I)-catalyzed enantioselective addition of nitromethane to methyl 4-oxobutanoate followed by hydrogenation and spontaneous lactamization gives (S)-5-hydroxypiperidin-2-one in 72% overall yield and 98% ee which compares favorably with previously reported methods.