Non-covalent interactions in the crystallization of the enantiomers of 1,7-dioxaspiro[5.5]undecane (olive fly sex pheromone) by enantiospecific cyclodextrin hosts, hexakis(2,3,6-tri-O-methyl)-α-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin

Abstract

The enantiomers of racemic olive fly sex pheromone 1,7-dioxaspiro[5.5]undecane (1) have been isolated by crystallization with enantiospecific cyclodextrin hosts: (S)-(1) crystallizes with heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMβCD) and (R)-(1) with hexakis(2,3,6-tri-O-methyl)-α-cyclodextrin (TMαCD). The crystal structure of TMβCD/(S)-(1) from synchrotron radiation data at 100 K, determined for the first time, proves that TMβCD crystallizes with only the (S)-enantiomer from the racemic mixture. Comparison with the 100 K structure of TMαCD/(R)-(1) redetermined with synchrotron data has provided insight into the interactions between each of the hosts with the corresponding enantiomeric guests. Owing to the high resolution of the data and the unusually high quality of the crystals, localization of the H atoms has been achieved, a rare accomplishment for cyclodextrin X-ray structures. This made possible, apart from the geometry of the complexes, the detailed description of a five-membered-ring water cluster with very well ordered hydrogen bonding. The enantiospecificity exhibited by the described systems reveals the subtle differences of the weak intermolecular forces involved in the selective binding of the two optical antipodes by the two hosts. The binding geometry in the two complexes is different, but it is effected in both by numerous host–guest C—H...O interactions, resulting from induced fit of the hosts toward each of the enantiomeric guests. In TMαCD/(R)-(1) two of these H...O host–guest distances, directed toward the acetal O atoms defining the chirality of the guest, are much shorter than the rest and also shorter than all the H...O distances in TMβCD/(S)-(1). Moreover, (R)-(1) interacts not only with the enclosing host, but with other hosts in the crystal lattice, in contrast to (S)-(1) in the TMβCD/(S)-(1) complex which is isolated inside channels formed by the host molecules. The above differences are reflected in the much higher binding constant of TMαCD/(R)-(1) compared with that of TMβCD/(S)-(1) (∼6800 and ∼935 M−1, respectively), determined by NMR in aqueous solution, and the ability of TMαCD to selectively precipitate (R)-(1) from racemic (1) in much higher yield than TMβCD precipitates (S)-(1).