DFT study on the reaction of the α-amino acid anion catalyzed by the aldehyde: Decarboxylation vs. intramolecular CO2 transfer

It is well known that the substituent effect has a great impact on the reaction mechanism. In this paper, basing on the density functional theory (DFT) method, we have carried out a systematic theoretical study about the reaction of the amino acid anion catalyzed by the aldehyde, where the amino group can react with the aldehyde to produce the imine. Two reaction pathways have been assumed: one is the direct decarboxylation; the other is the intramolecular CO2 transfer. It is found that substituents R1 (from the amino acid) on the α-carbon of the carboxylate and R2 (from the aldehyde) adjacent to the CN bond have crucial influence upon the reaction pathway. When the substituent has π-system, such as Ph, NO2, CN and CO2Et, the decarboxylation is prior to the intramolecular CO2 transfer. On the other hand, when the substituent has not π-system, such as Me, i-Pr, t-Bu, Cl, and OMe, the intramolecular CO2 transfer has an advantage over the decarboxylation. Whichever pathway the reaction proceeds in, electron-withdrawing substituent plays a obvious role in promoting, while the electron-donating substituent has the opposite effect.