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 (1R,2R)-(-)-1,2-diaminocyclohexane and (1R,2R)-(-)-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 beta-nitroalcohols with high enantioselectivity (ee, similar to 99%) were achieved in the case of 2-fluorobenzaldehyde in similar to 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).