Solvation-Induced Helicity Inversion of Pseudotetrahedral Chiral Copper(II) Complexes Anne-Christine Chamayou, † Gamall Makhlouﬁ, ‡ Laurence A. Naﬁe, § Christoph Janiak, ‡ and Steﬀen Lü deke* ,† † Institut fü r Pharmazeutische Wissenschaften, Universitä t Freiburg, Albertstr. 25, D-79104 Freiburg, Germany ‡ Institut fü r Anorganische Chemie und Strukturchemie, Universitä t Dü sseldorf, Universitä tsstr. 1, D-40225 Dü sseldorf, Germany § Department of Chemistry, Syracuse University, Syracuse, New York 13244-4100, United States * S Supporting Information ABSTRACT: The helicity of four-coordinated nonplanar com- plexes is strongly correlated to the chirality of the ligand. However, the stereochemical induction of either the Δ- or the Λ- conﬁguration at the metal ion is also modulated by environmental factors that change the conformational distribution of ligand rotamers. Calculation of the potential energy surface of bis{(R)-N- (1-(4-X-phenyl)ethyl)salicylaldiminato-κ 2 N,O}copper(II) with X = Cl at the density functional theory level showed a clear dependence of the helicity-determining angle θ between the two coordination planes on the relative population of diﬀerent ligand conformers. The inﬂuence of diﬀerent substituents (X = H, Cl, Br, and OCH 3 ) on complex helicity was studied by determination of the absolute conﬁguration at the metal ion in complexes with either (R)- or (S)-conﬁgured ligands. X-ray single-crystal analysis showed that (R)-conﬁgured ligands with H, Cl, Br induce Δ, while OCH 3 - substituted (R)-conﬁgured ligands induce Λ in the solid state. According to vibrational circular dichroism and electronic circular dichroism studies in solution, however, all tested complexes with (R)-ligands exhibited a propensity for Δ, with high diastereomeric ratio for X = Cl and X = Br and moderate diastereomeric ratio for X = H and X = OCH 3 substituted ligands. Therefore, solvation of copper complexes with X = OCH 3 goes along with helicity inversion. This solid-state versus solution study demonstrates that it is not suﬃcient to determine the chiral-at-metal conﬁguration of a compound by X-ray crystallography alone, because the solution structure can be diﬀerent. This is particularly important for the use of chiral-at-metal complexes as catalysts in stereoselective synthesis. ■ INTRODUCTION Diﬀerent from pairs of enantiomers, for diastereomers there exists an energy di ﬀerence that renders one of them thermodynamically favorable over the other. This energy diﬀerence can cause chirality transfer from a primary to a newly formed chiral center. In organic synthesis kinetic eﬀects may play an important role, too. 1 If stable bonds, such as carbon-carbon bonds, are formed, one diastereomer cannot be easily interconverted into the other. However, if weaker interactions are involved in the formation of an additional chiral center, chiral induction depends on thermodynamic equilibria. Examples for thermodynamically driven diastereose- lectivity are the formation of suprachiral aggregates, such as ﬁbrillary structures, 2 host-guest systems with guest-speciﬁc helicity, 3 and chiral-at-metal complexes, 4 provided that the ligand-metal coordination bonds are weak and labile enough to allow for a thermodynamic equilibrium. In such chiral-at- metal complexes the metal-centered conﬁguration Δ or Λ (Scheme 1) 5 can be induced by the (R)- or (S)-chirality of the ligand. 4a,6 Studies on chiral-at-metal complexes, and steric factors that govern the diastereoselectivity on metal-centered chirality formation, had initially been motivated by their important role in asymmetric catalysis; a popular example is the chirality of octahedral complexes of trivalent metals with binaphthalene- derived ligands. 7 The Δ/Λ-conﬁguration can often be determined in a straightforward way. In the solid state, it is easily revealed by X-ray crystallography, making use of resonant (anomalous) scattering of the metal ion. 8 Solutions of chiral-at- metal complexes can be studied by chiroptical methods, such as electronic circular dichroism (ECD), 9 vibrational circular dichroism (VCD), 10 or the measurement of the optical rotation. 11 CD arises from the diﬀerence in absorption of left and right circularly polarized light. In chiral-at-metal complexes this is due to a helical disposition of transition dipoles in a chiral molecule. 12 Metal-ligand or metal-metal transitions excited by UV or visible light may result in characteristic signals in the ECD, whose sign is indicative of the metal Received: November 7, 2014 Published: February 19, 2015 Article pubs.acs.org/IC © 2015 American Chemical Society 2193 DOI: 10.1021/ic502661u Inorg. Chem. 2015, 54, 2193-2203