ABSTRACT Metal‐organic frameworks (MOFs) provide unique catalytic environments through steric confinement imposed by their pores that govern reactivity, but concomitantly limit complex multicomponent transformations. Here, we first report a crystallography‐guided design of intrinsically dynamic MOFs that overcome this longstanding challenge. A crystallography–catalysis feedback loop with dimensionality and ligand‐flexibility tuning built a homologous Zn‐MOF series, revealing intrinsically dynamic, layer‐pillared Zn‐Bpe as the optimal catalyst. Mechanistic studies with a ligand‐substituted rigid analogue, host‐guest binding, density functional theory (DFT), and ab initio molecular dynamics (AIMD) reveal an adaptive catalytic mechanism where guests induce in situ framework dynamics, enhancing the diffusion of the substrates and the activity of the catalytic center. This dynamicity enables efficient and selective multicomponent couplings, exhibiting broad substrate tolerance and functional group compatibility, including a tandem domino Petasis reaction. Our findings establish intrinsic dynamicity as a generalizable design principle in MOF catalysis, balancing accessibility, selectivity, and structural integrity in complex transformations.
Jia et al. (2026) studied this question.