Mechanism and Origins of Selectivity in the Supramolecular [Ga₄L₆]^12–-Catalyzed Aza-Prins Reaction: The Mechanistic Studies

The mechanism, reactivity, and selectivity of the aza-Prins reaction in both the bulk solution and under [Ga4L6]12- (L = N,N-bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene) supramolecular catalysis were studied by means of theoretical calculations. In bulk solution, the steric effect and donor–acceptor interaction which favor the parallel-conformation transition state, in the selectivity-determining cyclization step, account for the observed chemoselectivity that leads to the alcohol product. While under the [Ga4L6]12– catalysis, the host–guest noncovalent interaction and confinement effect are more critical and make the vertical-conformation transition state more favorable, i.e., switch the chemoselectivity of the reaction that leads to the piperidine product. The presented calculations explain the reactivities of substrates by the cavity size-determined guest recognition. The computational findings are in good agreement with experiment. This work sheds light on development of more efficient and selective supramolecular catalysis.