HENRY REACTION CATALYZED BY COPPER(I) COMPLEXES OF A NEW PYRIDINE CONTAINING MACROCYCLIC LIGAND

The Henry or nitroaldol reaction has received much attention as a valuable tool for the formation of C-C bonds [1]. The reaction couples nitroalkanes with carbonyl compounds in the presence of a base giving β-nitroalcohols that are useful intermediates in the synthesis of relevant biologically active compounds. Recent studies in our research group demonstrated the efficacy of Cu(I) complexes derived from novel macrocyclic ligands containing a pyridine ring (PC-L) in the cyclopropanation reaction of various alkenes [2]. The excellent results obtained prompted us to verify the application of such Cu(I) complexes in the Henry reaction. We report here the synthesis of the new macrocyclic ligand 2 (Scheme 1) and the application of the corresponding Cu(I) complex as Lewis acid catalyst in the condensation between aldehydes and nitroalkanes. The best results in terms of chemical yields were obtained with in situ formed 1:1 ligand 2:Cu(OTf) complex (from [Cu(OTf)]2•C6H6) in dichloromethane at room temperature and in the presence of substoichiometric amount of a tertiary amine. Noteworthy, no trace of competitive side-reaction products were ever detected. [1] Henry, L. Hebd. Seances. Acad. Sci. 1895, 120, 1265–1268. Luzzio, F. A. Tetrahedron 2001, 57, 915–945 [2] Caselli, A.; Cesana, F.; Gallo, E.; Casati, N.; Macchi, P.; Sisti, M.; Celentano, G.; Cenini, S. Dalton Trans. 2008, 4202.