College of Chemistry, Chemical Engineering and Materials Science, Soochow University , Suzhou 215123, PR China.
J Org Chem. 2017 Dec 15;82(24):13109-13114. doi: 10.1021/acs.joc.7b02168. Epub 2017 Nov 21.
A mechanism study of quinine-squaramide catalyzed enantioselective aza-Friedel-Crafts (aza-F-C) reaction is described using density functional theory (DFT). The most favorable pathway is obtained through the discussions of four possible modes of hydrogen bond interactions, in which the nucleophile is activated by the squaramide N-H groups (N-Ha and N-Hb) and the electrophile binds to the protonated amine by hydrogen bonding. Meanwhile, we have also studied the energy barrier of the stereocontrolling transition states that might play a role of stereoselectivity. In addition, noncovalent interaction (NCI) analyses show a series of favorable cooperative noncovalent interactions, including N-H···O and C-H···F hydrogen-bonding, and π···π interactions. The strong interactions and lower barrier were found for TS3, indicating the preference for the R-configuration adduct, which is in good agreement with the experimental observations.
采用密度泛函理论（DFT）研究了奎宁-脒催化的对映选择性氮杂弗里德尔-克拉夫茨（aza-F-C）反应的机理。通过讨论四种可能的氢键相互作用模式，得到了最有利的途径，其中亲核试剂被脒 N-H 基团（N-Ha 和 N-Hb）激活，而亲电试剂通过氢键与质子化的胺结合。同时，我们还研究了立体控制过渡态的能垒，它可能对立体选择性起作用。此外，非共价相互作用（NCI）分析表明存在一系列有利的协同非共价相互作用，包括 N-H···O 和 C-H···F 氢键以及π···π相互作用。对于 TS3，发现了较强的相互作用和较低的势垒，表明 R-构型加成物具有优势，这与实验观察结果一致。
