Understanding the Reactivity and Selectivity of Fluxional Chiral DMAP‐Catalyzed Kinetic Resolutions of Axially Chiral Biaryls

Fluxional chiral DMAP‐catalyzed kinetic resolutions of axially chiral biaryls were examined using density functional theory. Computational analyses lead to a revised understanding of this reaction in which the interplay of numerous non‐covalent interactions control the conformation and flexibility of the active catalyst, the preferred mechanism, and the stereoselectivity. Notably, while the DMAP catalyst itself is confirmed to be highly fluxional, electrostatically driven π⋅⋅⋅π+ interactions render the active, acylated form of the catalyst highly rigid, explaining its pronounced stereoselectivity. Non‐covalent interactions impact every aspect of the fluxional chiral DMAP‐catalyzed kinetic resolution of BINOL derivatives, from locking the conformation of the acylated catalyst and steering the reaction toward a nucleophilic pathway to controlling the stereoselectivity.