Although bromodifluoromethane （BrCF2H） is a simple and readily available fluorine source, direct formation of difluoromethylated arenes with BrCF2H has not been reported. Herein, we describe an efficient method to a...Although bromodifluoromethane （BrCF2H） is a simple and readily available fluorine source, direct formation of difluoromethylated arenes with BrCF2H has not been reported. Herein, we describe an efficient method to access difluoromethylated arenes through a nickel-catalyzed difluoromethylation of arylboronic acids with BrCF2H. The reaction exhibits high efficiency, good functional group tolerance and broad substrate scope, thus providing an efficient route for applications in drug discovery and development. Preliminary mechanistic studies reveal that a difluoromethyl radical is involved in the reaction.展开更多
Difluoromethylated alkynes are a versatile synthon for the diversity-oriented synthesis of difluoromethyl compounds that are of great interest in life and materials sciences.However,the catalytic cross-coupling for th...Difluoromethylated alkynes are a versatile synthon for the diversity-oriented synthesis of difluoromethyl compounds that are of great interest in life and materials sciences.However,the catalytic cross-coupling for the synthesis of difluoromethylated alkynes remains challenging,despite impressive achievements made in the cross-coupling reactions for alkynes,including the Sonogashira reaction.Here,we report a palladium difluorocarbene involvement in catalytic coupling with terminal alkynes,representing a new mode of conjugation reaction,which circumvents the radical pathway usually encountered during the coupling of alkynes with fluoroalkyl electrophiles.The reaction uses inexpensive and abundant industrial raw material chlorodifluoromethane(ClCF_(2)H)as the difluorocarbene precursor,and features cost-effectiveness,excellent functional group tolerance,and broad substrate scope,including synthesis of drug-like complex molecules.Our mechanistic studies showed a unique catalytic pathway of this process,in which additive hydroquinone plays a pivotal role in promoting the reaction.展开更多
基金This work was financially supported by the National Natural Science Foundation of China （Nos. 21425208, 21672238, 21332010, and 21421002）, the Strategic Priority Research Program of Chinese Academy of Sciences （No. XDB20000000）, and SIOC.
文摘Although bromodifluoromethane （BrCF2H） is a simple and readily available fluorine source, direct formation of difluoromethylated arenes with BrCF2H has not been reported. Herein, we describe an efficient method to access difluoromethylated arenes through a nickel-catalyzed difluoromethylation of arylboronic acids with BrCF2H. The reaction exhibits high efficiency, good functional group tolerance and broad substrate scope, thus providing an efficient route for applications in drug discovery and development. Preliminary mechanistic studies reveal that a difluoromethyl radical is involved in the reaction.
基金Project supported by the National Natural Science Foundation of China(No.31401289)the Zhejiang Provincial Natural Science Foundation of China(No.LQ12C10001)the Education Department of Zhejiang Province(No.Y201122219),China
基金This research was made possible as a result of a generous grant from the National Natural Science Foundation of China(nos.21931013,21991122,21672238,and 21421002)the Strategic Priority Research Program of the Chinese Academy of Sciences(no.XDB20000000).
文摘Difluoromethylated alkynes are a versatile synthon for the diversity-oriented synthesis of difluoromethyl compounds that are of great interest in life and materials sciences.However,the catalytic cross-coupling for the synthesis of difluoromethylated alkynes remains challenging,despite impressive achievements made in the cross-coupling reactions for alkynes,including the Sonogashira reaction.Here,we report a palladium difluorocarbene involvement in catalytic coupling with terminal alkynes,representing a new mode of conjugation reaction,which circumvents the radical pathway usually encountered during the coupling of alkynes with fluoroalkyl electrophiles.The reaction uses inexpensive and abundant industrial raw material chlorodifluoromethane(ClCF_(2)H)as the difluorocarbene precursor,and features cost-effectiveness,excellent functional group tolerance,and broad substrate scope,including synthesis of drug-like complex molecules.Our mechanistic studies showed a unique catalytic pathway of this process,in which additive hydroquinone plays a pivotal role in promoting the reaction.
