Cu(II)-Macrocylic [H₄]Salen Catalyzed Asymmetric Nitroaldol Reaction and Its Application in the Synthesis of α1-Adrenergic Receptor Agonist (R)-Phenylephrine

New chiral Cu (II) complexes 1 – 6 were generated in situ by the interaction of different sources of copper(II) salts with chiral monomeric and dimeric macrocyclic [H 4 ]salen ligands derived from (1 R,2 R )-(−)-1,2-diaminocyclohexane and (1 R,2 R )-(−)-1,2-diphenyl-1,2-diaminoethane with trigol-bis(aldehyde). A variety of aldehydes were found to be suitable substrates with nitromethane in the presence of chiral macrocyclic [H 4 ]salen complexes 1 – 6 for asymmetric nitroaldol reaction at RT. Excellent yields (98% with respect to the aldehyde) of β-nitroalcohols with high enantioselectivity (ee, ∼99%) were achieved in the case of 2-fluorobenzaldehyde in ∼20 h with the use of chiral mononuclear and dinuclear macrocyclic Cu(II) salen complexes 2 and 5 . Both chiral mononuclear and dinuclear macrocyclic [H 4 ]salen catalysts 2 - and 5 -mediated nitroaldol processes are recyclable (up to eight cycles with no significant loss in its performance).