Copper-Catalyzed Mechanochemical Racemization of BINOL

The mechanochemical racemization of enantiopure 1,1'-bi-2-naphthol (BINOL) is reported using copper(I) chloride and several nitrogen-donor ligands with a 30-fold solvent reduction compared to the solution-phase reaction. Systematic optimization of milling parameters, including ball number, vessel material, catalyst loading, and liquid-assisted grinding (LAG) agent, establishes that the Cu/ligand system is the primary driver of racemization. Weakly coordinating aprotic LAG agents deliver superior performance, with DCM performing the best in the tested LAG series. DCM may be substituted by a greener MeCN/toluene (78:22 v/v) mixture with comparable efficiency. Ex situ kinetic studies reveal sigmoidal enantiomeric excess vs. time profiles across most conditions, attributed to an induction period preceding mobile interfacial layer formation. All conditions converge to a plateau of ∼5% ee, proposed to arise from a kinetically trapped Cu-ligand-BINOL complex under solid state conditions. These findings establish mechanochemistry as a viable and sustainable platform for the racemization of configurationally stable atropisomers.