Kinetics and Mechanism of Enantioselective Cu-Catalyzed Alcohol Silylation

The enantioselective Cu-catalyzed dehydrogenative Si–O coupling of secondary benzylic alcohols with (nBu)3SiH was investigated using a combination of in situ 1H/19F NMR spectroscopic reaction monitoring, isotopic labeling, kinetic modeling, and computational studies. Macrokinetic behavior is governed by substrate-inhibited L*CuOR·ROH resting states: rates rise with conversion when [(nBu)3SiH] > [ROH] and fall when [(nBu)3SiH] 2 generation and mitigates catalyst deactivation, increasing process safety and efficiency. Dynamic kinetic resolution, enabled by addition of a ruthenium racemization cocatalyst, results in reaction rates comparable to those of the faster enantiomer while improving overall efficiency.