C-H X-C bonds in alkyl halides drive reverse selectivities in confined spaces

Binding of non-activated alkyl halides (2-20) in water-soluble cavitand (1) through supramolecular forces is here reported, with emphasis on the role of size and polarizability of the halogen atom in the formation of intramolecular C-H hydrogen bonds in confined spaces. Rare reverse affinity in water (RI < RBr < RCl) is surprisingly observed for the more water-soluble short alkyl halides in dynamic open-ended containers. Competitive bindings and theoretical calculations confirm the unusual selectivity and the presence of C-H hydrogen bonds in non-activated systems for the first time, pointing out the importance and effect of subtle forces on molecular recognition in confined spaces.(c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.