Self-Assembly, Adaptive Response, and in,out-Stereoisomerism of Large Orthoformate Cryptands.

We report on triethylene glycol-based orthoformate cryptands, which adapt their bridgehead configurations in response to metal templates and intramolecular hydrogen bonding in a complex manner. In contrast to smaller 1.1.1-orthoformate cryptands, the inversion from out,out-2.2.2 to in,in-2.2.2 occurs spontaneously by thermal homeomorphic isomerization, i. e., without bond breakage. The global thermodynamic minimum of the entire network, which includes an unprecedented third isomer (in,out-2.2.2), could only be reached under conditions that facilitate dynamic covalent exchange. Both inversion processes were studied in detail, including DFT calculations and MD simulations, which were particularly helpful for explaining differences between equilibrium compositions in solvents chloroform and acetonitrile. Unexpectedly, the system could be driven to the in,out-2.2.2 state by using a metal template with a size mismatch with respect to the out,out-2.2.2 cage.