A New Catalyst for the Asymmetric Henry Reaction: Synthesis of β‑Nitroethanols in High Enantiomeric Excess

A new chiral tetrahydrosalen ligand has been designed and synthesized from <i>cis</i>-2,5-diaminobicyclo[2.2.2]octane. The complex generated in situ by the interaction of the ligand with (CuOTf)₂·C₆H₅CH₃ was an efficient catalyst for the asymmetric Henry reaction, producing nitroaldol products in high yield and good stereoselectivity. Henry reactions catalyzed by this tetrahydrosalen-Cu(I) complex led to syntheses of β-adrenergic blocking agents (<i>S</i>)-toliprolol, (<i>S</i>)-moprolol, and (<i>S</i>)-propanolol