Assembly of water-soluble, dynamic, covalent container molecules and their application in the room-temperature stabilization of protoadamantene

The thermodynamically controlled reactions of water-soluble tetraformylcavitand 2 with two equivalents of H₂N(CH ₂)_nNH₂ (n=2-4) in the presence of a suitable templating guest give hemicarceplexes 1 a-c·guest, the yield of which depends on the match between size and shape of the guest and that of the inner phase. These hemicarceplexes are dynamic and dissociate upon addition of acid and reform upon basification. In water, they exchange guests through temporary hydrolysis of imine bonds. To test 1 b as molecular reaction flask, 3-noradamantyldiazirine 6 was encapsulated and photolyzed at 350 nm to produce Bredt olefin protoadamantene 5 and 1-noradamantyldiazomethane 8 in a 4:1 ratio. Encapsulated protoadamantene is stable for days at room temperature in (CD ₃)₂SO/CD₃CN (t_1/2=5.5 days) and has a lifetime of several minutes in D₂O. Molecular nanoflask! Room-temperature stabilization of protoadamantene was achieved inside a water-soluble, dynamic, covalent, hemicarcerand nanoflask. The nanoflask spontaneously assembles from a cavitand and propylenediamine in water in the presence of 3-noradamantyldiazirine as a template (see scheme). Photolysis of the imprisoned diazirine yields the Bredt olefin, which survives for days at room temperature.