Chiral macrocyclic salen ligands 1'-3' derived from 1R,2R-(-)-1,2-diaminocyclohexane, 1R,2R-(+)-1,2-diphenyl-1,2-diaminoethane and (R)-(+)-1,1'-binaphthyl-2,2'-diamine with trigol bis aldehyde were prepared and characterized by microanalysis, H-1 NMR, UV/Vis. spectroscopy, optical rotation and mass spectroscopy. Highly enantioselective nitroaldol reaction of various aromatic and aliphatic aldehydes with nitromethane in presence of several bases were carried out in the presence of in situ generated Cu(I)/Cu(II) complexes with chiral macrocyclic salen ligands 1'-3' at RT. Excellent yields (up to 92% with respect to the aldehyde) of beta-nitroalcohols with high enantioselectivity (ee, similar to 95%) was achieved in case of 3-methoxy- and 4-nitrobenzaldehyde in ca. 30 h with the use of chiral macrocyclic salen ligands 3' with CuCl2 center dot 2H(2)O in presence of 2,6-lutidine as a base. Chiral macrocyclic salen catalyst 3 mediated nitroaldol process is recyclable (up to 8 cycles with no significant loss in its performance). This protocol is also used for the synthesis of enantiomerically pure (R)-phenylephrine (alpha 1-adrenergic receptor agonist) via asymmetric nitroaldol reaction of 3-methoxybenzaldehyde in three steps. (C) 2012 Elsevier B.V. All rights reserved.