The Mechanism of Aluminum-Catalyzed Meerwein−Schmidt−Ponndorf−Verley Reduction of Carbonyls to Alcohols

The mechanistic details of the Meerwein−Schmidt−Ponndorf−Verley (MSPV) reduction of
ketones to the corresponding alcohols were investigated both experimentally and computationally. Density
functional theory (DFT) was used to assess the energetics of several proposed pathways (direct hydrogen
transfer, hydridic, and radical). Our results demonstrate that a direct hydrogen transfer mechanism involving
a concerted six-membered ring transition state is the most favorable pathway for all calculated systems
starting from a small model system and concluding with the experimentally investigated BINOLate/Al/iPrOH/MePhCO system. Experimental values for the activation parameters of acetophenone reduction using
the BINOLate/Al/iPrOH system (ΔG# = 21.8 kcal/mol, ΔH# = 18.5 kcal/mol, ΔS# = −11.7 au) were
determined on the basis of kinetic investigation of the reaction and are in good agreement with the
computational findings for this system. Calculated and experimental kinetic isotope effects support the
concerted mechanism.