Computational Insight into the Mechanism of Mannich Reaction between Glycinate and Aryl NDiphenylphosphinyl Imine Catalyzed by N-Quaternized Pyridoxal

摘要

Recently,Chen et al.reported an asymmetric biomimetic Mannich reaction of tert-butyl glycinate(sub-1)with aryl Ndiphenylphosphinyl imine(sub-2)catalyzed by N-quaternized pyridoxal analogue(cat)(Chen et al.,Science,2018,360,1438– 1442).By utilizing Gaussian 09 program,we provide the detailed density functional theory(DFT,including B3LYP-D3 and M06-2X)investigations on the mechanisms of each section of the reaction with CHCl3 as implicit solvent.These cat,sub-1 and OH-if it exists can act as catalytic base and need to overcome relative free energy barrier of ~12,13.5 and 4.2 kcal/mol,respectively,to achieve α-carbon deprotonation.During the addition reaction,the most favorable transition structure was calculated to overcome a relative free energy barrier of 6.3 kcal/mol,verifying the bifunctional activation mode of cat.The final hydrolysis reaction starts with hydration to achieve protonation at the N atom of sub-2 portion and generates a carbinolamine.These computational results help one obtain deep understanding of the reaction mechanism and benefit future design of pyridoxal catalyst and similar biomimetic reaction.