Spontaneous macrocyclization through multiple dynamic cyclic aminal formation

The use of aminals in dynamic covalent chemistry is slightly underexplored, probably due to their inherent instability. Here we report the spontaneous [2+2] macrocyclization of tetrakis(aminals). Their unexpected stability and structural modularity, the dynamic nature of the connections and their water tolerance make them appealing systems for future applications as stimulus-responsive materials. The efficient cyclic aminal formation leads to the stereoselective synthesis of the corresponding [2+2] macrocycles, for which the dynamic covalent nature of the aminal bond can be controlled under specific conditions.