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 

机构地区：[1]State Key Laboratory of Elemento-Organic Chemistry,College of Chemistry,Nankai University,Tianjin 300071,China [2]Key Laboratory of Organofluorine Chemistry,Shanghai Institute of Organic Chemistry,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200032,China [3]Center of Basic Molecular Science,Department of Chemistry,Tsinghua University,Beijing 100084,China

出　　处：《Chinese Chemical Letters》2022年第5期2387-2390,共4页中国化学快报（英文版）

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

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 al.found 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 al.that the nucleophilic monofluoromethylation could be accomplished by employing lithium hexamethyldisi-lazide(LiHMDS)as a base.Herein,we present an in-depth computational investigation into the intrigu-ing effects of reagent structure and bases on the nucleophilic monofluoromethylation of aldehydes.The 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 structure.Employing 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.

关 键 词：Nucleophilic monofluoromethylation Fluoroalkylation reagent DFT calculations Thermodynamic effect Lone pair repulsion 

分 类 号：O621.25[理学—有机化学]