Anion Recognition DOI: 10.1002/anie.200906488 A Tridentate Halogen-Bonding Receptor for Tight Binding of Halide Anions** MohammedG. Sarwar, Bojan Dragisic, Sandeep Sagoo, and Mark S. Taylor* In memory of Keith Fagnou The selective recognition of anions by synthetic receptors is a problem that continues to fascinate chemists. [1] Hydrogen bonding has been the most frequently employed noncovalent interaction for the design of such receptors: molecular scaffolds that place H-bond donor groups in geometries suitable for an anion of interest demonstrate remarkable levels of selectivity and affinity. [2] Nonetheless, anion recep- tors that rely upon other noncovalent forces, including Lewis acid–base [3] and anion–p [4] interactions, have been investi- gated, with considerable success. Such studies have provided insight into the interactions employed, and have offered new opportunities to achieve selectivity in anion recognition. Here, we describe simple receptors capable of tight binding of halide anions through multidentate halogen bonding inter- actions (Figure 1). These represent the first systems in which the cooperative action of multiple halogen-bond donors is employed to achieve high-affinity binding in dilute solution. The selectivities of these receptors differ substantially from those of related receptors based on hydrogen bonding. Although halogen bonds between electron-deficient orga- nohalides and electron donors were observed decades ago, it is only recently that the generality and utility of this non- covalent interaction have gained widespread appreciation. [5] Halogen bonding has now been established as a powerful strategy for self-assembly in condensed phases, and its implications in biological systems are emerging. [6] Anions, particularly halides, participate readily as halogen-bond acceptors in the solid state, [7] including examples of crystalline networks in which a single anion accepts multiple halogen bonds. [8] This last observation suggests that a multidentate halogen-bond donor capable of donating several halogen bonds in a convergent fashion might be capable of anion binding in dilute solution. [9] Designing such a receptor presented a challenge. Appli- cations of halogen bonding in self-assembly have relied extensively on para-substituted iodotetrafluorobenzene derivatives prepared by nucleophilic aromatic substitution (for example, 2a). [10] This strategy results in divergent arrays of halogen-bond donors useful for constructing noncovalent polymers as well as two- and three-dimensional networks. In contrast, it is poorly suited for orienting multiple donors in a convergent fashion for binding to a single acceptor as is generally required of a high-affinity host. [1, 2] The most successful example of anion binding by a halogen-bond donor achieved to date makes use of ion-pair recognition: receptor 2a shows a 20-fold higher affinity for sodium iodide than does control receptor 2b, indicating a modest but measurable increase in affinity resulting from halogen bond- ing of iodide to the iodoarene groups (Figure 1). [11] We chose to explore ortho-substituted iodoperfluoroar- enes as the basis for receptors capable of multidentate halogen bonding. Esters of 2,3,4,5-tetrafluoro-6-iodobenzoic acid (which is easily prepared on multigram scale in one step) [12] emerged as attractive targets (1a–1d, Figure 1): we anticipated that the electron-withdrawing carboxy group would promote halogen-bond donor ability, while enabling a straightforward receptor synthesis through coupling reac- tions of readily available diols and triols. [13] Receptors 1b and 1c were prepared to test the feasibility of bidentate halogen Figure 1. Structures of the multivalent halogen-bond donors 1a–1d, and the ion-pair receptor 2a of Resnati and co-workers (Ref. [11a]). [*] M. G. Sarwar, B. Dragisic, S. Sagoo, Prof. M. S. Taylor Department of Chemistry, Lash Miller Laboratories University of Toronto 80 St. George St., Toronto, ON M5S 3H6 (Canada) Fax: (+ 1) 416-978-8775 E-mail: mtaylor@chem.utoronto.ca Homepage: http://www.chem.utoronto.ca/staff/MST/taylorgroup [**] This work was funded by NSERC (Discovery Grants Program), the Canadian Foundation for Innovation, the Province of Ontario, Merck Research Laboratories (Canadian Academic Development Program), and the University of Toronto. We are grateful to Prof. Rebecca Jockusch for assistance and instrumentation used for the ESI-MS binding studies. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.200906488. Communications 1674  2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. Int. Ed. 2010, 49, 1674 –1677