The discovery of coronands and cryptands, organic compounds that can accommodate metal ions in a preorganized two- or three-dimensional environment, was a milestone in supramolecular chemistry, leading to countless applications from organic synthesis to metallurgy and medicine. These compounds are typically prepared via multistep organic synthesis and one of their characteristic features is the high stability of their covalent framework. Here we report the use of a dynamic covalent exchange reaction for the one-pot template synthesis of a new class of coronates and cryptates, in which acid-labile O,O,O-orthoesters serve as bridgeheads. In contrast to their classic analogues, the compounds described herein are constitutionally dynamic in the presence of acid and can be induced to release their guest via irreversible deconstruction of the cage. These properties open up a wide range of application opportunities, from systems chemistry to molecular sensing and drug delivery.

We demonstrate that acid-catalyzed orthoester exchange is a promising tool for applications in dynamic covalent and systems chemistry.

The integration of dynamic covalent bonds into macrocycles has been a tremendously successful strategy for investigating noncovalent interactions and identifying effective host-guest pairs. While numerous studies have focused on the dynamic responses of macrocycles and larger cages to various guests, the corresponding constitutionally dynamic chemistry of cryptands remains unexplored. Reported here is that cryptands based on orthoester bridgeheads offer an elegant entry to experiments in which a metal ion selects its preferred host from a dynamic mixture of competing subcomponents. In such dynamic mixtures, the alkali metal ions Li , Na , K , Rb , and Cs exhibit pronounced preferences for the formation of cryptands of certain sizes and donor numbers, and the selection is rationalized by DFT calculations. Reported is also the first self-assembly of a chiral orthoester cryptate and a preliminary study on the use of stereoisomers as subcomponents.

Dynamic covalent chemistry (DCC) is a vibrant research area that has extended its reach from supramolecular chemistry into fields as diverse as bioconjugation, materials science and systems chemistry. Because DCC crucially rests on reversible organic reactions, considerable effort has been invested in the development of new reactions of this type and the identification of new methods for facilitating existing processes. Our group has recently reported that orthoester exchange is a previously overlooked reversible reaction that is in principle suited for many applications of DCC. This microreview gives an overview on our ongoing work on orthoester exchange, and puts it into the context of previous studies on the related dynamic covalent chemistry of esters and acetals.