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DFT Study on the Mechanism of Amides to Aldehydes Using Cp2Zr(H)Cl

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journal contribution
posted on 11.01.2010, 00:00 by Juping Wang, Huiying Xu, Hui Gao, Cheng-Yong Su, Cunyuan Zhao, David Lee Phillips
Density functional theory (DFT) calculations at the B3LYP/6-31G(d,p) (LANL2DZ for Zr) level of theory were performed to elucidate the reaction mechanism for the reduction of amides to aldehydes using Cp2Zr(H)Cl as a reducer. In particular, a detailed study was done that involved a proposed iminium cation species in the reaction mechanism. Our calculations suggest the first step of the reaction is the insertion of the CO moiety into Zr−H through an “inside” mode of action that leads to the formation of a Zr−O intermediate that has been observed in previously reported experiments. Under anhydrous conditions, the cleavage of the O−C bond of the Zr−O intermediate results in the formation of an iminium cation, but this process is both kinetically and thermodynamically unfavorable. Nevertheless, under hydrous conditions, the cleavage of the O−C bond of the Zr−O intermediate leads to the formation of a highly active iminium cation intermediate, and this process occurs with the assistance of water hydrogen bonding. This step is also the rate-determining step, and the activation energy was determined to be 19.8 kcal/mol. Subsequently a water molecule attacks the iminium cation to produce an amine intermediate. Finally, the water-catalyzed elimination reaction occurs to yield the aldehyde product. Water hydrogen bonding plays an important role in assisting the cleavage of the O−C and the C−N bonds during the reaction. The above reaction mechanism indicates that the sources of the aldehyde-group oxygen and the hydrogen in the aldehyde product are H2O and Cp2Zr(H)Cl, respectively, which is consistent with the experimental observations of Georg and co-workers.