近日，河南师范大学Hai-Ming Guo及其研究组理性设计2-取代DMAP-N-氧化物作为酰基转移催化剂，用于动态动力学拆分吖内酯。 相关论文于2020年10月29日发表于国际顶尖学术期刊《美国化学会志》上。

研究人员展示了一个新的概念，手性转换2-取代DMAP到其DMAP-N-氧化物可以显著提高催化活性，同时仍可作为酰基转移催化剂。研究人员理性设计并合成了一种来自L-酪酰胺的新型手性2-取代DMAP-N-氧化物，将其用于动态动力学拆分吖内酯。使用简单的甲醇作为亲核试剂，可以以高产率（高达98%的产率）和对映选择性（高达96%的ee）产生多种L-氨基酸衍生物。此外,α-氘取代L-苯丙氨酸衍生物也能获得。

实验和DFT计算表明，在2-取代的DMAP-N-氧化物中，氧原子充当亲核位点，而N–H键充当H键供体。反应的高对映选择性受空间因素控制，苯甲酸的加入通过参与氢键桥的构建而降低了活化能。理论化学研究表明，只有充分考虑手性催化剂的攻击方向才能得到正确的计算结果。这项工作为利用吡啶环C2位置和发展手性2-取代DMAP-N-氧化物作为高效酰基转移催化剂铺平了道路。

附：英文原文

Title: Rational Design of 2-Substituted DMAP-N-oxides as Acyl Transfer Catalysts: Dynamic Kinetic Resolution of Azlactones

Author: Ming-Sheng Xie, Bin Huang, Ning Li, Yin Tian, Xiao-Xia Wu, Yun Deng, Gui-Rong Qu, Hai-Ming Guo

Issue&Volume: October 29, 2020

Abstract: A novel concept that conversion of chiral 2-substituted DMAP into its DMAP-N-oxide could significantly enhance the catalytic activity and still be used as an acyl transfer catalyst is presented. A new type of chiral 2-substituted DMAP-N-oxides, derived from l-prolinamides, has been rationally designed, facilely synthesized, and applied in the dynamic kinetic resolution of azlactones. Using simple MeOH as the nucleophile, various l-amino acid derivatives were produced in high yields (up to 98% yield) and enantioselectivities (up to 96% ee). Furthermore, α-deuterium labeled l-phenylalanine derivative was also obtained. Experiments and DFT calculations revealed that in 2-substituted DMAP-N-oxide, the oxygen atom acted as the nucleophilic site and the N–H bond functioned as the H-bond donor. High enantioselectivity of the reaction was governed by steric factors, and the addition of benzoic acid reduced the activation energy by participating in the construction of a H-bond bridge. The theoretical chemical study indicated that only when attack directions of the chiral catalyst were fully considered could the correct calculation results be obtained. This work paves the way for the utilization of the C2 position of the pyridine ring and the development of chiral 2-substituted DMAP-N-oxides as efficient acyl transfer catalysts.

DOI: 10.1021/jacs.0c09075

Source: https://pubs.acs.org/doi/10.1021/jacs.0c09075