Crystal Structure Evidence for the Directionality of Lone Pair-π interactions: Fact or Fiction?

The location of intermolecular lone pair atom contacts with C6F5X, where X = any atom, was evaluated using the Cambridge Structural Database (CSD). The results establish that it is not possible to distinguish the distribution of lone pair atoms in contact with this arene surface from an isotropic distribution of van der Waals contacts. In other words, the CSD provides no evidence for either the directionality or the existence of the lone pair-pi interaction with this electron-deficient arene. The current findings are in stark contrast to prior reports that crystal structure data provide (i) examples of lone pair-pi interactions and (ii) evidence that lone pair-pi interactions are strongly directional. Examination of the previous CSD analyses reveals that in every case the data had been misinterpreted. The most common mistake involves using search criteria to select subsets of contacts and then attaching significance to these selected contacts without the context of the entire contact distribution.