Effect of the regulation of quinine in Cinchona Base derived primary amine on the addition reaction of nitrostyrene with 2-methylpropionaldehyde

Abstract The Michael addition of nitrostyrene and 2-methylpropionaldehyde catalyzed via cinchona alkaloid-based primary amines (9-epi-QDA-R'') with the aid of benzoic acid have been carried out at the PCM(toluene)/B3LYP/6-311 + + G(2df,2p)//B3LYP/6-31G(d) level. The calculations showed that the whole reaction consisted of four consecutive steps: ⑴ the production of an imine ion intermediate, ⑵ an addition reaction between the imine ion and nitrostyrene, ⑶ the second proton transfer stage, and ⑷ hydrolysis and regeneration stage of the catalyst. The rate-determining step of the whole reaction is the addition process between the imine ion and nitrostyrene. The correlation calculations determined that 9-epi-QDA-R'' containing -NH electron-absorbing group in the quinine ring exhibit stronger activation than that containing -CH2 electron-donating group, while 9-epi-QDA-R'' with -NCONHPh electron-absorbing group in the quinine ring exhibit weaker activation than that containing -CH2 electron-donating group. Natural Bond Orbital analysis of atomic charges of the tertiary amine nitrogen in the quinine ring determined that the electron-absorbing group slightly reduce the negative charges on the nitrogen atom of the tertiary amine, which is favorable for the addition reaction of the imine ion to nitrostyrene. However, the negative charge on tertiary amine nitrogen is much reduced by the electron-absorbing substituents, which is not conducive to the addition reaction of nitrostyrene with the imine ion. Accordingly, the calculations exhibit that the charge distribution of the nitrogen atom of the tertiary amine influences the catalytic efficiency of the whole system.