Supramolecular Cage Architecture Dictates Reaction Trajectory: [Ga 4 L n 6 ] 12– Mediated Dienol Hydrogenation via Confinement-Induced Transition State Modulation

Confined catalysis offers valuable insights into selectivity control by mimicking enzymatic cavity catalysis, overcoming limitations of traditional catalytic systems. The synergy between transition metals and confined spaces enhances reactivity and selectivity that are otherwise difficult to attain. However, the encapsulation mechanisms, synergistic nature, and selectivity regulation remain poorly understood. This study examines 2,4-hexadiene-1-ol hydrogenation using [Ga 4 L n 6 ] 12– metallocages (L 1 = N , N ′-bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene; L 2 = N , N ′-(pyrene-1,6-diyl)bis(2,3-dihydroxybenzamide)) as catalysts. We employed molecular dynamics simulations and attach-pull-release methods to determine initial host–guest structures. Subsequent quantum chemical calculations elucidated the hydrogenation mechanism and selectivity variations across three catalytic conditions. DFT calculations revealed that complete hydrogenation predominates without metallocages or in large ones, whereas cis -2,5-monohydrogenation prevails in smaller metallocages. Cavity size critically influences regioselectivity and product distribution. Moreover, we observed a unique transition from ″full-″ to ″semiencapsulation″ reaction patterns. Our study clarifies the dynamics of transition metal-confined synergistic catalysis, identifies key selectivity inversion factors, and provides theoretical guidance for designing efficient, selective catalysts.