Metal-Free Electrochemical Oxidative Difluoroethylation/Cyclization of Olefinic Amides To Construct Difluoroethylated Azaheterocycles

Abstract

A new strategy of electrochemical oxidative difluoroethylation to generate difluoroethyl radical with sodium difluoroethylsulfinate (DFES-Na) has been reported for the first time. The method allows quick access to a variety of valuable difluoroethylated azaheterocycles including oxindoles and isoquinoline-1,3-diones via radical tandem difluoroethylation/cyclization in moderate to good yields. The electrochemical cyclopropyldifluoromethylation of N-arylacrylamides also works well using this strategy. Moreover, radical capture and cyclic voltammetry (CV) experiments are also carried out to determine the proposed mechanism.

Difluoroethylation Reactions of Organic Compounds

“…[28] The usage of a C/Pt electrode and applying In 2023, Tian and co-workers reported electrochemical difluoroethylation/cyclization of olefinic amides using sodium difluoroethylsulfinate (DFES-Na) as the MeCF 2 radical source (Scheme 11). [29] This protocol provided access to a variety of difluoroethylated oxindoles and isoquinoline-1,3-diones under metal-free and oxidant-free conditions. The difluoroethylated products were formed upon MeCF 2 radical addition to an alkene, followed by 6-membered ring-forming homolytic aromatic substitution.…”

Electrochemically Promoted Oxydifluoroethylation of Alkenes for the Synthesis of Difluoroethylated Benzoxazines and Lactones

“…Therefore, we focus on the development of an efficient electrochemical method to produce difluoroethyl radical and apply it to the construction of difluoroethylated heterocycles, especially benzoxazines and lactones, which are prevalent in organic chemistry, pharmacy, and biology [15] . As our continuous studies on the difluoroethylation, [16c] we report our success in electrochemical oxidative difluoroethylation of alkenes for the synthesis of difluoroethylated benzoxazines and lactones by using MeCF 2 SO 2 Na as MeCF 2 radical precursor under metal‐free and chemical oxidant–free conditions.…”

Electrochemical Radical Tandem Difluoroethylation/Cyclization of Unsaturated Amides to Access MeCF2-Featured Indolo/Benzoimidazo [2,1-a]Isoquinolin-6(5H)-ones

“…On the other hand, electrochemical synthesis has also attracted much attention due to the advantages of avoiding the usage of chemical oxidants and reductants [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Very recently, much progress in electrochemical difluoroethylation has been made by Hu [ 24 ] and our group [ 25 , 26 ]. Although these methods have provided innovative transformations, the preparation of CF 2 Me-substituted polycyclic compounds has not been achieved.…”