The activity and stereoselectivity of asymmetric catalytic reactions often depend on small free-energy differences among structurally similar intermediates and transition states. Conformational variations, noncovalent interactions, solvent effects, and competition among different reaction pathways further complicate mechanistic elucidation. Computational chemistry enables the molecular-level characterisation of key species and transition states that are difficult to observe experimentally, thereby providing important insights into chiral induction and selectivity control. Drawing on representative studies from our work on asymmetric organocatalysis [1–4], this talk will illustrate how density functional theory, conformational searching, distortion–interaction and noncovalent interaction analysis can be used to establish catalytic cycles, identify selectivity-determining steps, compare competing transition states, and uncover the physical origins of stereoselectivity. These studies demonstrate that the value of computational chemistry extends beyond reproducing experimental results: it translates subtle energy differences into understandable molecular mechanisms and advances asymmetric catalysis from retrospective explanation towards testable prediction.

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