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 cis-2,5-diaminobicyclo[2.2.2]octane. The complex generated in situ by the interaction of the ligand with (CuOTf)(2) center dot 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 beta-adrenergic blocking agents (S)-toliprolol, (S)-moprolol, and (S)-propanolol.