Organic & Biomolecular Chemistry PAPER Cite this: Org. Biomol. Chem., 2015, 13, 2170 Received 24th November 2014, Accepted 16th December 2014 DOI: 10.1039/c4ob02470b www.rsc.org/obc Stereoelectronic effects: a simple yet powerful tool to manipulate anion affinity† Masoud Samet, a Alireza Fattahi b and Steven R. Kass* a Different strategies are employed in designing strong and selective anion receptors but stereoelectronic effects have been largely ignored. In this work, the stereo configuration of a non-interacting ether is found to have a large impact of more than two orders of magnitude on the binding of a rigid diol with tetrabutylammonium chloride in acetonitrile-d 3 . A favorable carbon–oxygen dipole and an intramolecular C–H⋯OH hydrogen bond in an equatorially substituted ether is found to be energetically more important than a stabilizing hydrogen bond in the corresponding axially oriented alcohol. IR spectroscopy is also used to probe the structures of the bound complexes and several binding motifs are identified. Introduction Anion recognition is critical in a number of biological pro- cesses such as enzyme catalysis 1,2 and anion transport through cellular phospholipid bilayers. 3–7 Drawing inspiration from these pathways, chemists have mimicked nature to develop anion transporters, 8–11 metal-free catalysts, 12–15 and sensors. 16,17 A variety of strategies have been employed in designing ion receptors that make use of hydrogen bond networks, 15,18–20 electrostatic effects 21 and inductive stabilization. 22–26 Stereoelectronic effects are largely unex- plored, 20,27,28 however, even though they play an important role in many enzymatic transformations (e.g., serine proteases, lysozyme, and [NiFe]-hydrogenases). 29–32 The orientation of substituents that directly interact with an anion can have a large impact on the binding constant of a host compound. 20,27,33 For instance, syn-triphenol 1s uses all three hydroxyl groups to interact with chloride anion and the resulting association constant with tetrabutylammonium chloride (TBACl) in acetonitrile-d 3 is 1.3 × 10 5 M −1 . In contrast, the anti-rotamer 1a can only make use of two hydrogen bonds in the 1 : 1 complex with TBACl, and its binding constant of 240 M −1 corresponds to a reduction of a little more than 500 fold. 20 The effect of the spatial arrangement of a non-interact- ing group is little studied but Kondo, Kobayashi, and Unno reported on the two anomers of a D-ribose derivative (2). 28 As one might expect, small K 2β /K 2α ratios were observed for a variety of anion salts in polar (CD 3 CN) and nonpolar (CDCl 3 ) solvents. These values varied from 5–34, but a larger difference of 130 was obtained in the latter noncompetitive solvent with tetrabutylammonium dihydrogen phosphate. scyllo-Inositol derivatives (3, Fig. 1) can serve as Brønsted and hydrogen bond catalysts and anion recognition Fig. 1 scyllo- and myo-Inositol structures used previously (3 and 4) and in this work (5). † Electronic supplementary information (ESI) available: Binding determination data, IR, 1 H and 13 C NMR spectra and computed geometries and energies are provided (22 pages). See DOI: 10.1039/c4ob02470b a Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA. E-mail: kass@umn.edu b Department of Chemistry, Sharif University of Technology, Tehran, Iran 2170 | Org. Biomol. Chem. , 2015, 13, 2170–2176 This journal is © The Royal Society of Chemistry 2015 Published on 17 December 2014. Downloaded by University of Minnesota - Twin Cities on 18/09/2016 23:42:47. View Article Online View Journal | View Issue