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Computational Insight into the Mechanism of Mannich Reaction between Glycinate and Aryl N ‐Diphenylphosphinyl Imine Catalyzed by N‐Quaternized Pyridoxal
Author(s) -
Yang Yongsheng,
Zhang Yan,
Yang Junxia,
Xue Ying
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202001606
Subject(s) - chemistry , imine , catalysis , deprotonation , bifunctional , reaction mechanism , transition state , pyridoxal , computational chemistry , aryl , medicinal chemistry , mannich reaction , organic chemistry , ion , alkyl , phosphate
Recently, Chen et al. reported an asymmetric biomimetic Mannich reaction of tert ‐butyl glycinate ( sub‐1 ) with aryl N ‐diphenylphosphinyl 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 CHCl 3 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.