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

Abstract

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.

Transfer Hydrogenation Including the Meerwein‐Ponndorf‐Verley Reduction

“…When employing a catalyst with deuterium at the a-positions of the isopropoxide ligands (17), complete retention of the deuterium was observed. A computational study using the density functional theory comparing the six-membered transition state (as in Scheme 20.3, the direct transfer mechanism) with the hydride mechanism (Scheme 20.3, the hydride mechanism) supported the experimental results obtained [36]. A similar mechanism has been proposed for the MPV alkynylations [37] and cyanations [38].…”

Zr‐TUD‐1: A Lewis Acidic, Three‐Dimensional, Mesoporous, Zirconium‐Containing Catalyst

“…[2][3][4][5] The mechanism of both the homogenous and the heterogeneous MPVO reaction has been shown to proceed through a carbon-to-carbon hydride transfer from an alcohol to a ketone or aldehyde (Scheme 1). [6][7][8] The heterogeneous catalysts can also be used to racemise benzylic alcohols; in this case, however, the reaction occurs through an addition-elimination process. [6,9] Moreover, Lewis acids catalyse such important reactions as the carbon-carbon bond forming Prins reaction.…”

Comparing Neutral (Monometallic) and Anionic (Bimetallic) Aluminum Complexes in Hydroboration Catalysis: Influences of Lithium Cooperation and Ligand Set

“…Thus 4 may be considered a masked hydride complex in hydroboration of ketones. Elaborating this step further, it is pertinent to consider the Meerwein–Ponndorf–Verley (MPV) reduction,11a, 12, 13 employing aluminum alkoxides as the hydride source to reduce ketones. Two competing mechanisms have been studied in silico 13.…”

“…Elaborating this step further, it is pertinent to consider the Meerwein–Ponndorf–Verley (MPV) reduction,11a, 12, 13 employing aluminum alkoxides as the hydride source to reduce ketones. Two competing mechanisms have been studied in silico 13. The first involves β‐hydride transfer from the alkoxide ligand giving a high energy Al–H intermediate, which can then follow the pathway represented in Scheme 1.…”