A State of Independents: Rationalizing the High Zˈ Crystal Structures of Shikimate Esters

Zˈ is a parameter used to denote the number of symmetry-independent molecules in the asymmetric unit of a crystal structure. High Zˈ (>1) crystal structures are relatively uncommon and are thought to arise through competition between intermolecular interactions of similar strength. As such high Zˈ crystal structures are challenging to predict and new examples are valuable in improving understanding in the field. Herein, we report the X-ray crystal structures of a series of shikimate esters, the asymmetric units of which exhibit high Zˈ values. Of special interest is the crystal structure of methyl shikimate, the asymmetric unit of which comprises 12 independent molecules; Zˈ = 12. This uncommonly large Zˈ value arises through a combination of factors, including the intrinsic homochirality of the molecule, the conformational inflexibility of the cyclohexene ring, the presence of multiple hydrogen bonding motifs, and both the cis- and trans-conformers of the ester moiety. Comparison of the X-ray crystal structures of shikimic acid, methyl shikimate, ethyl shikimate, and iso-propyl shikimate suggests that instances of high Zˈ in this series correlate with specific hydrogen bonding motifs influenced by the steric bulk of the ester. The results of this study provide important insights into factors that influence the formation of organic crystal structures where the value of Zˈ is greater than 1.