Conformational landscape of a chiral crown ether: a vibrational circular dichroism spectroscopy and computational study Juan Ramón Avilés Moreno a,⇑ , Francisco Partal Ureña a , Juan Jesús López González a , Francisco Gámez b , Bruno Martínez-Haya b,⇑ a Department of Physical and Analytical Chemistry, Campus Las Lagunillas, University of Jaén, E-23071 Jaén, Spain b Department of Physical, Chemical and Natural Systems, Universidad Pablo de Olavide, E-41013 Seville, Spain article info Article history: Received 2 February 2012 Accepted 23 February 2012 abstract Herein we report a study of the most stable conformers of the chiral crown ether (all-S)-(18-crown-6)- 2,3,11,12-tetracarboxylic acid (18c6H 4 ), which constitutes a key building block for materials in asym- metric catalysis and enantiomeric separation. Infrared and vibrational circular dichroism spectroscopies are employed to characterize the vibrational modes of the 18c6H 4 molecule in a low polarity solvent (CDCl 3 ). The investigation covers a broad range of wavenumbers (800–4000 cm À1 ) and focuses particu- larly on the O–H, C–H, C@O and C–O stretching modes and on the C–O–H bending mode, which yield the most intense IR and VCD signals. The experimental results are combined with a computational confor- mational survey and structure optimization at the B3LYP/6-311++G(2d,2p) level. The conformational landscape of 18c6H 4 is found to be governed by bowl-like structures sustained by various types of H-bonding arrangements of the carboxylic side chains with each other and with the central crown ether ring. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Crown ethers constitute benchmark substrates for the selective binding of cationic species and have played a key role in the development of supramolecular chemistry over the past three decades. 1–3 The cyclic backbone characteristic of crown ethers forms inclusion complexes with metal cations, 4,5 ammonium or protonated primary and secondary amines. 6–10 An important class of substituted crown ethers incorporates chiral structural features capable of assisting enantiomeric discrimination. A large number of previous works devoted to the development of chiral selectors for electrophoresis 11 and of stationary phases for high performance liquid chromatography have been based on crown ether substrates. 12–14 The crown ether structures most extensively investigated in this field are based on the benchmark molecule, 18-crown-6-2,3,11,12-tetracarboxylic acid (18c6H 4 ). This molecule can be derived from tartaric acid; 3 the enantiomer relevant to this work is represented in Figure 1. Previous work has investigated the structure of 18c6H 4 and of its non-covalent complexes with various chiral guests, by means of X-ray diffraction, 6,15 nuclear magnetic resonance, 16–18 and further spectroscopic methods, in particular electronic circular dichroism. 19–21 Herein we report the conformational landscape of the free (all-S)-18c6H 4 enantiomer in a low polarity medium (CDCl 3 ). Infrared absorption (IR) and vibrational circular dichroism (VCD) spectroscopies are employed in combination with quantum chemistry calculations with the aim of providing insight into the intrinsic intramolecular interactions that sustain the most stable conformers of this chiral substrate. To the best of our knowledge, VCD spectroscopy has not previ- ously been applied to investigate chiral crown ether conformations in solution. In a closely related study, Shen et al. 14 have recently examined the HPLC separation of an aromatic chiral amine using (all-R)-(18c6H 4 ) as the stationary phase. The two amine enantio- mers were characterized using VCD spectroscopy and different 0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetasy.2012.02.013 ⇑ Corresponding authors. E-mail addresses: jraviles@ujaen.es (J.R.A. Moreno), bmarhay@upo.es (B. Martínez- Haya). HO O O O O HO O O O O OH O OH O 1 2 3 4 5 6 Cx2 Cx1 Cx3 Cx4 Figure 1. Schematic representation of the molecule (all-S)-(18-crown-6)-2,3,11,12- tetracarboxylic acid (referred to as 18c6H 4 throughout the paper). For the sake of discussion, the carboxylic arms are denoted as Cx1–Cx4 and the ether ring oxygens are numbered 1–6 as indicated. Tetrahedron: Asymmetry 23 (2012) 294–299 Contents lists available at SciVerse ScienceDirect Tetrahedron: Asymmetry journal homepage: www.elsevier.com/locate/tetasy