Mechanistic Study of theN‑Quaternized Pyridoxal-Catalyzed Biomimetic Asymmetric Mannich Reaction: Insights into the Origins of Enantioselectivity and Diastereoselectivity

Xianlu Cui^‡a, QianqianLi^‡a, Lei Yao^a, Yanshun Ma^a, Lixiong Zhang^b, Chuanbao Zhang^c, Lili Zhao^a*

^aInstitute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China.Email:ias_llzhao@njtech.edu.cn

^bCollege of Chemical Engineering, State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing 211816, China

^cCollege of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, China.

ABSTRACT:Density functional theory (DFT) calculations have been performed to gain insight into the catalytic mechanism of the N-quaternizedpyridoxals (i.e.,1a)mediatedbiomimeticasymmetricMannichreaction oftert-butyl glycinate3withN-diphenylphosphinyl imine2ato give thediamino acid ester4ain high yield with excellent enantiomeric and diastereomeric selectivity(Science 2018, 360, 1438).The study reveals that the whole catalysis can be characterized via three stages: (i)the catalyst1areact with thetert-butyl glycinate3generatethe active carbanion complexIM3. (ii)IM3thenreacts with theN-diphenylphosphinyl imine2agivingtheimineintermediateIM8.(iii)IM8undergoes hydrolysis to give the final product anti-4aand regenerate the catalyst1afor the next catalytic cycle.Each stage is kinetically and thermodynamically feasible for experimental realization.Thehydrolysis step in the stage IIIis predicted to be therate-determining step (RDS) during the wholecatalytic cycle.Furthermore,theorigins of the enantioselectivity and diastereoselectivityfor thetarget reaction,as well asthedeactivationof thecatalyst1b,arealso discussed.

J. Org. Chem.2021, 86, 9, 6592–6599影响因子：4.335

论文链接：https://pubs.acs.org/doi/10.1021/acs.joc.1c00381