Tetrahydropyran-Based Hybrid Dipeptides as Asymmetric Catalysts for Michael Addition of Aldehydes to β-Nitrostyrenes

A new series of hybrid dipeptide-like organocatalysts based on pyranoid E- or -amino acids and proline have been prepared for the asymmetric Michael addition of aldehydes to -nitrostyrenes. The reaction proceeds under mild conditions to afford a wide range of -nitroaldehydes with up to 98% yield and up to 96% ee. These dipeptides are bifunctional organocatalysts, with a proline at the N-terminus and a carboxylic acid at the C-terminus. The tetrahydropyran unit embedded in the E- or -amino acid induces a well-defined conformation that is responsible for the catalysis. These dipeptides represent a new type of organocatalyst with a large number of possibilities to modulate their reactivity and selectivity.