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/(i)PrOH/MePhC=O system. Experimental values for the activation parameters of acetophenone reduction using the BINOLate/Al/(i)PrOH system (DeltaG# = 21.8 kcal/mol, DeltaH# = 18.5 kcal/mol, DeltaS# = -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.
Cohen
Revital
R
Department of Organic Chemistry, Weizmann Institute of Science, 76100 Rechovot, Israel.
Graves
Christopher R
CR
Nguyen
SonBinh T
ST
Martin
Jan M L
JM
Ratner
Mark A
MA