A general method for the synthesis of bench-stable bis(difluoromethyl)pentacoordinate phosphoranes has been developed.The reaction is rapid,operationally simple,and easily scalable.The pentacoordinate phosphoranes can...A general method for the synthesis of bench-stable bis(difluoromethyl)pentacoordinate phosphoranes has been developed.The reaction is rapid,operationally simple,and easily scalable.The pentacoordinate phosphoranes can generate both difluoromethyl radical(·CF_(2)H)and difluorocarbene(:CF_(2))intermediates.Thus,a variety of fluoroalkylation transformations havebeen achieved by·CF_(2)H,such asoxidativedifluoromethylation of electron-deficient heterocycles,nickel/photoredox dual-catalyzed difluoromethylation of aryl bromides,and photoredox difluoromethylation of alkenes,or by:CF_(2),such as gem-difluorocyclopropanation of alkenes,base-promoted difluoromethylation of heteroatom nucleophiles,Pd-catalyzed difluoromethylation of arylboronic acids,and Cu-mediated trifluoromethylation of aryl iodides(via:CF_(2) and recombined CF_(3)-).These fluoroalkylation methods have been successfully applied to late-stage fluoroalkylation of drugs and drug-like molecules.展开更多
The fluoroalkyl fragment plays a vital role in various fields such as pharmaceuticals and materials science, and has a significant impact on human life not only on the present but also in the future. The insertion of ...The fluoroalkyl fragment plays a vital role in various fields such as pharmaceuticals and materials science, and has a significant impact on human life not only on the present but also in the future. The insertion of fluoroalkyl groups into the chemical skeletons can cause considerable alternations in the chemical, physical and biological properties of molecules, which has attracted numerous scientists from different fields. This review focuses on N-heterocyclic carbene(NHC)-catalyzed fluoroalkylation reactions, providing a detailed analysis and summary of the achievements in the past two decades. Many successful examples clearly indicate that NHCs can catalyze the tranformation of fluoroalkylation reagents with various electronic characteristics, whether electrophilic, nucleophilic, or radical precursors. Herein, the fluoroalkylation reactions are classified based on different catalytic modes of NHCs: Lewis base catalysis, Umploung catalysis, radical catalysis and others. Meanwhile, by refining and systematically studying the contribution of NHC catalysis in fluoroalkylation reactions, this review is expected to provide valuable insights and enlightenment for related fields.展开更多
The development of synthetic methods for the introduction of the fluorine atom and fluoroalklyl groups into organic molecules has gained increased attention.Synthetic organic chemists have recently jumped into the fie...The development of synthetic methods for the introduction of the fluorine atom and fluoroalklyl groups into organic molecules has gained increased attention.Synthetic organic chemists have recently jumped into the field of organofluorine chemistry and have thus made significant contributions.Furthermore,these newly developed methods are typically safer and more effective than the traditional methods.In this review,wewill summarize the representative contributions of new reagents and reactions developed in the past decade.展开更多
Ⅰ. INTRODUCTION Perfluoroalkylation of alkenes is one of the most important methods for industrial as well as laboratory syntheses of a variety of organofluorine compounds. It is usually induced by light, heat or rad...Ⅰ. INTRODUCTION Perfluoroalkylation of alkenes is one of the most important methods for industrial as well as laboratory syntheses of a variety of organofluorine compounds. It is usually induced by light, heat or radical initiators. A few of transition metals and their complexes have been shown to be able to catalyse the addition reaction展开更多
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 nucleo...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.展开更多
We report a Ni-catalyzed three-component cross-electrophile coupling of alkynes with alkenyl halides and fluoroalkyl halides to generate fluoroalkyl-incorporated 1,3-dienes.This mild and operationally simple protocol ...We report a Ni-catalyzed three-component cross-electrophile coupling of alkynes with alkenyl halides and fluoroalkyl halides to generate fluoroalkyl-incorporated 1,3-dienes.This mild and operationally simple protocol is distinguished by its broad substrate scope and excellent chemo-,regio-,and stereo-selectivity,offering a new and organometallic agent-free platform for the construction of fluoroalkyl-incorporated diene motifs.Preliminary mechanistic studies have been conducted to probe the potential reaction pathway.展开更多
Herein, we report an unprecedented regiospecific oxidative Mizoroki-Heck type reaction for the synthesis of α-difluoromethyl homoallylic alcohols. The reaction shows broad substrate scopes and high functional group t...Herein, we report an unprecedented regiospecific oxidative Mizoroki-Heck type reaction for the synthesis of α-difluoromethyl homoallylic alcohols. The reaction shows broad substrate scopes and high functional group tolerance. Late-stage functionalization of complex biologically active molecules demonstrates the synthetic potential of this transformation. Mechanistic study supports the involvement of MnBr_(2) catalyzed radical 1,2-silyl transfer.展开更多
基金supported by National Natural Science Foundation of China(grant no.21901196)the Natural Science Basic Research Plan in Shaanxi Province of China(grant nos.2020JQ-016 and 2021GXLH-Z-096)+1 种基金the Fundamental Research Funds for the Central Universities(grant no.xhj032021007-01)Xi’an Jiaotong University(grant no.71211920000001).
文摘A general method for the synthesis of bench-stable bis(difluoromethyl)pentacoordinate phosphoranes has been developed.The reaction is rapid,operationally simple,and easily scalable.The pentacoordinate phosphoranes can generate both difluoromethyl radical(·CF_(2)H)and difluorocarbene(:CF_(2))intermediates.Thus,a variety of fluoroalkylation transformations havebeen achieved by·CF_(2)H,such asoxidativedifluoromethylation of electron-deficient heterocycles,nickel/photoredox dual-catalyzed difluoromethylation of aryl bromides,and photoredox difluoromethylation of alkenes,or by:CF_(2),such as gem-difluorocyclopropanation of alkenes,base-promoted difluoromethylation of heteroatom nucleophiles,Pd-catalyzed difluoromethylation of arylboronic acids,and Cu-mediated trifluoromethylation of aryl iodides(via:CF_(2) and recombined CF_(3)-).These fluoroalkylation methods have been successfully applied to late-stage fluoroalkylation of drugs and drug-like molecules.
基金supported by the National Natural Science Foundation of China (21871160, 21672121, 22071130)the Bayer Investigator Fellowthe Fellowship of Tsinghua-Peking Center for Life Sciences (CLS)。
文摘The fluoroalkyl fragment plays a vital role in various fields such as pharmaceuticals and materials science, and has a significant impact on human life not only on the present but also in the future. The insertion of fluoroalkyl groups into the chemical skeletons can cause considerable alternations in the chemical, physical and biological properties of molecules, which has attracted numerous scientists from different fields. This review focuses on N-heterocyclic carbene(NHC)-catalyzed fluoroalkylation reactions, providing a detailed analysis and summary of the achievements in the past two decades. Many successful examples clearly indicate that NHCs can catalyze the tranformation of fluoroalkylation reagents with various electronic characteristics, whether electrophilic, nucleophilic, or radical precursors. Herein, the fluoroalkylation reactions are classified based on different catalytic modes of NHCs: Lewis base catalysis, Umploung catalysis, radical catalysis and others. Meanwhile, by refining and systematically studying the contribution of NHC catalysis in fluoroalkylation reactions, this review is expected to provide valuable insights and enlightenment for related fields.
基金support from the National Natural Science Foundation of China(grant nos.21991121,21931013,21925105,22025103,and 21961142015)the National Key Research and Development Program of China(grant no.2021YFF0701700).
文摘The development of synthetic methods for the introduction of the fluorine atom and fluoroalklyl groups into organic molecules has gained increased attention.Synthetic organic chemists have recently jumped into the field of organofluorine chemistry and have thus made significant contributions.Furthermore,these newly developed methods are typically safer and more effective than the traditional methods.In this review,wewill summarize the representative contributions of new reagents and reactions developed in the past decade.
文摘Ⅰ. INTRODUCTION Perfluoroalkylation of alkenes is one of the most important methods for industrial as well as laboratory syntheses of a variety of organofluorine compounds. It is usually induced by light, heat or radical initiators. A few of transition metals and their complexes have been shown to be able to catalyse the addition reaction
基金supported by the Natural Science Foundation of China(Nos.22122104,21933004 and 21702098).
文摘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.
基金financial support provided by the National Natural Science Foundation of China(Nos.21991123,21971036,21901036)the Shanghai Rising-Star Program(No.20QA1400200)。
文摘We report a Ni-catalyzed three-component cross-electrophile coupling of alkynes with alkenyl halides and fluoroalkyl halides to generate fluoroalkyl-incorporated 1,3-dienes.This mild and operationally simple protocol is distinguished by its broad substrate scope and excellent chemo-,regio-,and stereo-selectivity,offering a new and organometallic agent-free platform for the construction of fluoroalkyl-incorporated diene motifs.Preliminary mechanistic studies have been conducted to probe the potential reaction pathway.
基金the National Natural Science Foundation of China (No. 21901191)the Fundamental Research Funds for the Central Universities and Wuhan University for financial support
文摘Herein, we report an unprecedented regiospecific oxidative Mizoroki-Heck type reaction for the synthesis of α-difluoromethyl homoallylic alcohols. The reaction shows broad substrate scopes and high functional group tolerance. Late-stage functionalization of complex biologically active molecules demonstrates the synthetic potential of this transformation. Mechanistic study supports the involvement of MnBr_(2) catalyzed radical 1,2-silyl transfer.
