Noncovalent Modulation of Chemoselectivity in the Gas Phase Leads to a Switchover in Reaction Type from Heterolytic to Homolytic to Electrocyclic Cleavage

In the gas phase, thermal activation of supramolecular assemblies such as host–guest complexes leads commonly to noncovalent dissociation into the individual components. Chemical reactions, for example of encapsulated guest molecules, are only found in exceptional cases. As observed by mass spectrometry, when 1‐amino‐methyl‐2,3‐diazabicyclo[2.2.2]oct‐2‐ene (DBOA) is complexed by the macrocycle β‐cyclodextrin, its protonated complex undergoes collision‐induced dissociation into its components, the conventional reaction pathway. Inside the macrocyclic cavity of cucurbit[7]uril (CB7), a competitive chemical reaction of monoprotonated DBOA takes place upon thermal activation, namely a stepwise homolytic covalent bond cleavage with the elimination of N 2 , while the doubly protonated CB7⋅DBOA complex undergoes an inner‐phase elimination of ethylene, a concerted, electrocyclic ring‐opening reaction. These chemical reaction pathways stand in contrast to the gas‐phase chemistry of uncomplexed monoprotonated DBOA, for which an elimination of NH 3 predominates upon collision‐induced activation, as a heterolytic bond cleavage reaction. The combined results, which can be rationalized in terms of organic‐chemical reaction mechanisms and density‐function theoretical calculations, demonstrate that chemical reactions in the gas phase can be steered chemoselectively through noncovalent interactions.