Computational insights into the effects of reagent structure and bases on nucleophilic monofluoromethylation of aldehydes

作     者：Meng-Meng Zheng Hao-Dong Tan Yueqian Sang Xiao-Song Xue Jin-Pei Cheng Meng-Meng Zheng;Hao-Dong Tan;Yueqian Sang;Xiao-Song Xue;Jin-Pei Cheng

作者机构：State Key Laboratory of Elemento-Organic ChemistryCollege of ChemistryNankai UniversityTianjin 300071China Key Laboratory of Organofluorine ChemistryShanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200032China Center of Basic Molecular ScienceDepartment of ChemistryTsinghua UniversityBeijing 100084China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2022年第33卷第5期

页      面：2387-2390页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：supported by the Natural Science Foundation of China(Nos.22122104 21933004 and 21702098) 

主　　题：Nucleophilic monofluoromethylation Fluoroalkylation reagent DFT calculations Thermodynamic effect Lone pair repulsion 

摘      要：Although fluorobis(phenylsulfonyl)methane(FBSM)and its cyclic analog 2-fluoro-1,3-benzodithiole-1,1,3,3-tetraoxide(FBDT)possess similar physicochemical properties,Shibata et *** that FBSM failed to undergo nucleophilic monofluoromethylation of aldehydes regardless of the reaction conditions at-tempted(using various organic and inorganic bases).However,it was later discovered by Hu et *** the nucleophilic monofluoromethylation could be accomplished by employing lithium hexamethyldisi-lazide(LiHMDS)as a ***,we present an in-depth computational investigation into the intrigu-ing effects of reagent structure and bases on the nucleophilic monofluoromethylation of *** computations reveal the 1,4-diazabicyclo[2.2.2]octane(DABCO)catalyzed nucleophilic monofluoromethy-lation of benzaldehyde with acyclic FBSM is a thermodynamically unfavorable process mainly due to the destabilizing O···O lone pair repulsions in FBSM product,whereas such repulsion could be largely avoided in FBDT product because of its constrained five-membered ring *** LiHMDS as a base can not only facilitate the nucleophilic monofluoromethylation via Li–O interactions but also render the monofluoromethylation of benzaldehyde with FBSM thermodynamically favored.