Synthesis of copper(I) complexes with new chiral nitrogen donor macrocyclic ligands and their use in asymmetric catalysis

Copper complexes play an important role in asymmetric catalysis and a number of different chiral ligands has been reported in the last decades. Among those, chiral C2-symmetric bidentate ligands have enjoyed a remarkable success in copper-catalyzed asymmetric cyclopropanation.1 This can be in part ascribed to the fact that fewer reaction channels are possible for the reaction, which simplifies the prediction of chiral induction. Furthermore, the synthesis of the ligands is often simpler than for C1-symmetric compounds. Only recently, C1-symmetric N,N-ligands have been reported to give moderate results in these reactions.2 We have recently found that copper(I) complexes of the new C1-symmetric pyridine-based 12 membered tetraaza macrocyclic (Pc-L*) ligands are competent asymmetric catalysts in the cyclopropanation of differently substituted olefins employing ethyl diazoacetate (EDA) as carbene precursor.3 We report here the synthesis of new C1- and C2-symmetric Pc-L* macrocycles and their use for the same reaction. The designed synthetic path is very simple and take advantage of commercially available, enantiomerically pure, chiral amino-alcohols and/or primary amines. All the macrocycles could be obtained in moderate to good yields and have been fully characterized. Their copper(I) complexes showed excellent catalytic activities and in all cases a quantitative conversion of the starting EDA was observed to give the desired cyclopropane derivatives. Enantiomeric excesses up to 90% were obtained. Moreover, the obtained results allow for a direct comparison of the stereoselective outcome of the reaction between C1- and C2-symmetric ligands of the same molecular structure. ______________ References: 1. (a) Pfaltz, A. Acc. Chem. Res.., 1993, 26, 339. (b) Evans, D.A.; Woerpel, K.A.; Hinmann, M.M., Faul, M.M. J. Am. Chem. Soc. 1991, 113, 726. (c) Ito, K.; Katsuki, T. Tetrahedron Lett. 1993, 34, 2661. 2. (a) Teng, P.-F.; Tsang, C.-S.; Yeung, H.-L.; Wong, W.-L.; Kwong, H.-L. J. Organomet. Chem. 2006, 691, 5664. (b) Borriello, C., Cucciolito, M.E.; Panunzi, A.; Ruffo, F. Tetrahedron: Asymm. 2001, 12, 2467. 3. Caselli, A.; Cesana, F.; Gallo, E.; Casati, N.; Macchi, P.; Sisti, M.; Celentano, G.; Cenini, S.. Dalton Trans. 2008, 4202.