Self-assembly of dynamic orthoester cryptates

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.

. Slow exchange on the NMR timescale. K > 20 can be deduced for this competition experiment, because at equimolar addition not even traces of [Na + o-Me2-1.  Zeolite type A (molecular sieves 4Å) is clearly responsible for the exchange of lithium against sodium (which was also observed by 1 H, 23 Na, 7 Li NMR spectroscopy and mass spectrometry) 2 . Acid (TFA) seems to be not necessary for this cation exchange to occur and an equilibrium between Li + /Na + is reached even before orthoester exchange is initiated. The concentration of sodium ions was also measured, but poor quality data was obtained due to the ubiquity of sodium in glassware and reagents. (See also Supporting Table 3 7 Li NMR spectroscopy and mass spectrometry) 2 . Acid (TFA) seems to be not necessary for this cation exchange to occur and an equilibrium between K + /Na + is reached even before orthoester exchange is initiated. The concentration of sodium ions was also measured, but poor quality data was obtained due to the ubiquity of sodium in glassware and reagents. (See also Supporting Table 3   HPLC chromatogram (210 nm). b) ESI + mass spectrum for peak at 4.18 min. c) ESImass spectrum for peak at 6.17 min.

Supplementary Notes
Supplementary Note 1

Calculation of kobs based on EXSY data:
Using the equations shown below, where IAA, IBB (½) and ICC are the diagonal peak integrals and IAB, IBA, IBC and ICB are the cross-peak integrals, we obtain the magnetization rate r, from which we calculate k which is the sum of the forward, k1, and backward, k-1, pseudo-first order rate constants for the cation

Reagents and instruments
All commercially purchased reagents were used without further purification. Molecular sieves were dried for 3 days at 150 °C under reduced pressure (10 -2 mbar) before use. CDCl3, DMSO-d6, MeCN-d3 and benzene-d6 were stored over molecular sieves. NMR spectra were recorded on Bruker Avance 300 (

Preparation of stock solutions
To achieve a high level of stoichiometric accuracy and adequate exclusion of moisture, metal salts and diethylene glycol were added from stock solutions that were dried over molecular sieves prior to addition of orthoester and acid catalyst.
To obtain the acid stock solution, trifluoroacetic acid (TFA, 240 µmol, 18.4 µL) was topped up with CDCl3 to obtain a total volume of 2 mL.

General procedure
Molecular sieves 4 Å (1 g) were added to 6.0 mL of the salt stock solution and the reaction mixture was left to stand at room temperature for 16 h. The orthoester (0.12 mmol) and 10 µL of the acid stock solution (1 mol%) was added and the reaction mixture was shaken. Every 24 h, 10 µL of the acid stock solution (1 mol%) was added to keep the exchange reaction active (molecular sieves slowly transform the acid catalyst into inactive anhydride and/or esters) and the reaction progress was monitored regularly by 1 H NMR spectroscopy.

Exclusion of moisture
Molecular sieves were dried by heating for 3 days at 150 °C under reduced pressure (10 -2 mbar). All solvents were dried over molecular sieves for at least 24 hours. All orthoester exchange reactions (catalyzed by TFA) were carried out under nitrogen. After the acid is quenched (e.g., by addition of triethylamine or basic aluminum oxide), many of the orthoesters described herein were found to be unusually stable against water (see Supplementary Figure 2).
[Na + o-Me2-1.1.1]BArFwas prepared according to the general procedure from NaBArF, trimethyl orthoacetate and diethylene glycol. After 5 days, the solvent was removed under reduced pressure and the title compound was obtained as a colourless solid in 67% yield. Further purification could be achieved by passing a solution of the crude mixture in chloroform through a short plug of silica gel or by crystallization (e.g. slow diffusion of cyclopentane  8, 162.3, 161.8, 161.3, 135.1, 129.7, 129.4, 129.1, 128.9, 128.8, 126.2, 123.5, 120.8, 117.7, 113.0, 69.2, 62.0, 17.7 ppm. 11  [Na + o-Et2-1.1.1]BArFwas prepared according to the general procedure from NaBArF, trimethyl orthopropionate and diethylene glycol. After 5 days, the solvent was removed under reduced pressure and the title compound was obtained as a colourless solid in 52% yield. Further purification could be achieved by passing a solution of the crude mixture through a short plug of aluminium oxide or silica gel.