Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]iso...Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.展开更多
A photocatalyst-free photoinduced radical difluoromethylation approach for the convenient synthesis of 3-CF_(2)H-coumarins from alkynoates by difluoromethyl phenoxathiinium salt(PT-CF_(2)H^(+)BF_(4)^(-))was developed....A photocatalyst-free photoinduced radical difluoromethylation approach for the convenient synthesis of 3-CF_(2)H-coumarins from alkynoates by difluoromethyl phenoxathiinium salt(PT-CF_(2)H^(+)BF_(4)^(-))was developed.This transformation in-volves radical difluoromethylation/5-exo spirocyclization/ester migration rearrangement cascade process and features mild reaction conditions,broad substrate scope and good functional groups tolerance.Using this method,a wide range of alkynoates was successfully converted to desired 3-CF_(2)H-coumarins in moderate to good yields.展开更多
Herein,we describe a nickel-catalyzed reductive decarboxylative difluoromethylation reaction of alkenes using inexpensive and easy-to-handle difluoroacetic anhydride(DFAA)/pyridine N-oxide reagent system.A variety of ...Herein,we describe a nickel-catalyzed reductive decarboxylative difluoromethylation reaction of alkenes using inexpensive and easy-to-handle difluoroacetic anhydride(DFAA)/pyridine N-oxide reagent system.A variety of C(sp^(3))-CF_(2)H containing compounds were prepared through a hydrodifluoromethylation process.Besides,various gem–difluoroalkenes bearing CF_(2)H group were synthesized via defluorinative reductive cross-coupling process from trifluoromethyl-substituted alkenes using this new reaction system.Difluoroacetic anhydride has been then extended to other common alkyl anhydrides,and the corresponding hydroalkylation and defluoroalkylation processes have been successfully achieved.This method features broad substrate scope,good functional group tolerance as well as high efficiency.展开更多
A facile and highly efficient approach for selective O-difluoromethylation of 1,3-diones by recently developed bench-stable S-(difluoromethyl)sulfonium salt was described.And a broad range of difluoromthyl enol ethers...A facile and highly efficient approach for selective O-difluoromethylation of 1,3-diones by recently developed bench-stable S-(difluoromethyl)sulfonium salt was described.And a broad range of difluoromthyl enol ethers were readily accessed in good to excellent yields under mild reaction conditions.Mechanistic studies revealed that the O-difluoromethylation reaction proceeds mainly via a difluorocarbene pathway.展开更多
Deuteriodifluoromethyl(CF_(2)D)is a challenging and important functional group due to difficult deuterium incorporation and lack of effective precursor reagents.Herein,we report a bench-stable reagent,deuteriodifluoro...Deuteriodifluoromethyl(CF_(2)D)is a challenging and important functional group due to difficult deuterium incorporation and lack of effective precursor reagents.Herein,we report a bench-stable reagent,deuteriodifluoromethyl phosphine(DDFP)from cheap deuterium source for selectivity deuteriodifluoromethylation of azines with a high deuterium incorporation yield.The late-stage modification of complex molecules further confirmed the potential of this reagent for practical applications.We expect that our reagent to find applications in synthesis of isotope-labelled molecules of interests for drug-discovery and related ilucidation of mechanism of action.展开更多
Practical,undirected and selective catalytic functionalization of unactivated arenes remains a challenging problem in organic synthesis.We herein report a bioinspired L-cystine-derived ligand BCPOM/Fe-enabled innate C...Practical,undirected and selective catalytic functionalization of unactivated arenes remains a challenging problem in organic synthesis.We herein report a bioinspired L-cystine-derived ligand BCPOM/Fe-enabled innate C-H difluoromethylation of unactivated arenes as limiting reagents with stable and inexpensive BrCF_(2)CO_(2)Et as the difluoromethylation source in high efficiency.Notably,this method uses environmentally benign H_(2)O_(2) as the sole oxidant,and enables late-stage functionalization and exceptionally functional-group tolerance,even including oxidation-labile aldehyde,phenolic hydroxy,primary amine,and boronic acid groups,which is difficult to access by current means.展开更多
The pursuit of sustainable and environmentally benign synthetic methods continues to challenge organic chemists. Herein, we introduce a magnetoredox system for tri- and difluoromethylation of isocyanides and N-arylacr...The pursuit of sustainable and environmentally benign synthetic methods continues to challenge organic chemists. Herein, we introduce a magnetoredox system for tri- and difluoromethylation of isocyanides and N-arylacrylamides using a rotating magnetic field and steel rods. This magnetoredox approach enables facile synthesis of functionalized phenanthridines and oxindoles without the need for catalysts and additives under mild conditions. Such a system potentially represents an attractive strategy for selective formation of bonds through multifaceted regulation of magnetic intensity, rotating frequency, and rod size.展开更多
Herein,we report a photo-induced,metal-/additive-free protocol for the difluoromethylation of N-heteroaromatics with[bis(difluoroacetoxy)iodo]benzene as the difluoromethylation reagent.The protocol affords difluoromet...Herein,we report a photo-induced,metal-/additive-free protocol for the difluoromethylation of N-heteroaromatics with[bis(difluoroacetoxy)iodo]benzene as the difluoromethylation reagent.The protocol affords difluoromethylated N-heteroaromatics in moderate to good yield(up to 91%).The transformation is compatible with a wide range of substrates and has good tolerance towards various functional groups.Moreover,the synthetic value of this method is further demonstrated by applications in gram-scale synthesis and the late-stage functionalization of biologically important molecules.展开更多
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
Difluoromethyltri（n-butyl）ammonium chloride 1 was found to be an effective difluorocarbene reagent for O-, S-, N-, C-difluoromethylation under basic conditions. It is particularly remarkable that, when only 1.2 equi...Difluoromethyltri（n-butyl）ammonium chloride 1 was found to be an effective difluorocarbene reagent for O-, S-, N-, C-difluoromethylation under basic conditions. It is particularly remarkable that, when only 1.2 equivalent of reagent 1 was used, the difluoromethylated products were obtained in moderate to excellent yields.展开更多
CF_(2)H-containing molecules play pivotal roles in diverse fields from medicinal chemistry to materials science. However, the application of existing CF_(2)H reagents as a source of CF_(2)H radical is limited by their...CF_(2)H-containing molecules play pivotal roles in diverse fields from medicinal chemistry to materials science. However, the application of existing CF_(2)H reagents as a source of CF_(2)H radical is limited by their reactivity and preparation. Herein, we develop a simple and general visible-light-catalyzed radical difluoromethylation reaction of alkenes, dienes, and heteroaromatics using commercially available, easy-to-handle, and low-cost difluoroacetic anhydride as the CF_(2)H reagent. This scalable protocol enables the convenient synthesis of a range of CF_(2)H-containing compounds under mild conditions, exhibiting a broad substrate scope and functional group tolerance. Potential applications are further demonstrated by gram-scale synthesis, sunlight experiments, derivatization experiments as well as the synthesis of bioactive molecules.展开更多
The divergent reductive cross-coupling with an ambident electrophile is rare.Previously,we demonstrated a nickel-catalyzed reductive 2-pyridination of aryl iodides with difluoromethyl 2-pyridyl sulfone(2-Py SO_(2)CF_(...The divergent reductive cross-coupling with an ambident electrophile is rare.Previously,we demonstrated a nickel-catalyzed reductive 2-pyridination of aryl iodides with difluoromethyl 2-pyridyl sulfone(2-Py SO_(2)CF_(2)H)via selective C(sp^(2))-S bond cleavage of the sulfone by using a phosphine ligand.In this communication,we report a novel nickel-catalyzed reductive coupling of aryl iodides and 2-Py SO_(2)CF_(2)H reagent,which constitutes a new method for aromatic difluoromethylation.The use of a tridentate terpyridine ligand is pivotal for the selective C(sp^(3))-S bond cleavage of the sulfone.This method employs readily available nickel catalyst and 2-Py SO_(2)CF_(2)H as the difluoromethylation reagent,providing a facile access to difluoromethylarenes under mild reaction conditions without pre-generation of arylmetal reagents.展开更多
Visible-light induced direct C–H difluoromethylation of quinoxalinones with 2-((difluoromethyl)sulfonyl)benzo[d]thiazole has been developed for the first time.A broad range of quinoxalinones were well tolerated and r...Visible-light induced direct C–H difluoromethylation of quinoxalinones with 2-((difluoromethyl)sulfonyl)benzo[d]thiazole has been developed for the first time.A broad range of quinoxalinones were well tolerated and reacted with difluorosulfone smoothly to give the corresponding products in moderate to good yields.Notably,no external photocatalyst or oxidant was required,which provides a practical and green protocol to access difluoromethylated quinoxalinones.Finally,the control experiments demonstrated a radical mechanism,and the density functional theory(DFT)calculations indicated the radicals were generated through the formation of an electron donoracceptor(EDA)complex.展开更多
Highly regiodivergent copper-catalyzed allylic/propargylic difluoromethylation reactions by employing different ligands are described. When 5,6-dimethyl-1,10-phenanthroline was used as the ligand, exclusively α-diflu...Highly regiodivergent copper-catalyzed allylic/propargylic difluoromethylation reactions by employing different ligands are described. When 5,6-dimethyl-1,10-phenanthroline was used as the ligand, exclusively α-difluoromethylated products were obtained, while γ-selective difluoromethylated products were generated when N-heterocyclic carbene-SIPr was used as the ligand. Likewise, high α- vs. γ-selectivities were achieved in the presence of similar copper catalysts for the reactions of propargyl bromides. Moreover, a copper-catalyzed asymmetric allylic difluoromethylation reaction with moderate to good enantioselectivity by the use of chiral ligands was developed.展开更多
Difluoromethyl ethers are formed through mechanochemical reactions of alcohols with difluorocarbene in a mixer mill.The protocol could be applied to primary,secondary,and tertiary alcohols,yielding the corresponding p...Difluoromethyl ethers are formed through mechanochemical reactions of alcohols with difluorocarbene in a mixer mill.The protocol could be applied to primary,secondary,and tertiary alcohols,yielding the corresponding products in excellent yields(up to 99%)after 1 h reaction time at room temperature.The transformations proceeded under solvent-free reaction conditions,followed by product purification by filtration,which drastically reduced the amount of waste generated during the process.展开更多
The active Cu(Ⅰ)species Q^(+)[Cu^(Ⅰ)(CF_(2)CO_(2)Et)(Cl)]^(-)1a and Q^(+)[Cu^(Ⅰ)(CF_(2)CO_(2)Et)_(2)]^(-)1b(Q=Ph_(4)P),which played an important role in the copper mediated ethoxycarbonyl difluoromethylation of org...The active Cu(Ⅰ)species Q^(+)[Cu^(Ⅰ)(CF_(2)CO_(2)Et)(Cl)]^(-)1a and Q^(+)[Cu^(Ⅰ)(CF_(2)CO_(2)Et)_(2)]^(-)1b(Q=Ph_(4)P),which played an important role in the copper mediated ethoxycarbonyl difluoromethylation of organic halides,have been isolated and characterized for the first time.Stoichiometric reaction showed complex 1b is much more reactive than 1a.Furthermore,while oxidative addition of complex 1b with aryl iodide resulted in the formation of the reductive elimination product without the observation of the Cu(Ⅲ)intermediate,the oxidative addition of iodoacetronitrile to 1b successfully generated Cu(Ⅲ)intermediates that reductively eliminate to give the products.Building on the stoichiometric reaction,a copper-catalyzed ethoxycarbonyl difluoromethylation of benzylic,allylic halides was developed.Additionally,it has been found that complex 1b serves as a powerful ethoxycarbonyl difluoromethylation reagent capable of ethoxycarbonyl difluoromethylating a variety of electrophiles including(hetero)aryl electrophiles,alkyl electrophiles and acid chloride,disulfide.Moreover,the oxidative ethoxycarbonyl difluoromethylation of complex 1b with various lithium n–butyl(hetero)aryl boronic acid pinacol esters has been achieved in the presence of an oxidant.展开更多
Stereoselective approach for preparation ofα-difluoromethylα-propargylamines has been developed.1,2-Addition of lithium acetylides to diverse chiral difluoromethylated（S）-N-tert-butanesulfinyl ketimines by using T...Stereoselective approach for preparation ofα-difluoromethylα-propargylamines has been developed.1,2-Addition of lithium acetylides to diverse chiral difluoromethylated（S）-N-tert-butanesulfinyl ketimines by using Ti（O^iPr）_4 as catalyst and THF as solvent afforded N-tert-butanesulfinamides in good to excellent yields（51-93%） and good diastereoselectivities（dr.85：15 to 93：7）.The N-tert -butanesulfinyl group can be readily cleaved under mild acidic condition（4 mol/L HCl in dioxane） to provide the correspondingα-difiuoromethylα-propargylamine in excellent yields（90-95%）.展开更多
Two discrete octahedral metallo-supramolecular cages were designed and constructed by using truxene-based pyridine L with enPd(NO_(3))_(2)or enPt(NO_(3))_(2),followed by detailed NMR,MS,UV absorption,and fluorescence ...Two discrete octahedral metallo-supramolecular cages were designed and constructed by using truxene-based pyridine L with enPd(NO_(3))_(2)or enPt(NO_(3))_(2),followed by detailed NMR,MS,UV absorption,and fluorescence spectroscopy.Owing to the determined cavity size and excellent optical performance of cages,the resulting supramolecular cages were confirmed to be the light-harvesting system based on Foster resonance energy-transfer(FRET).The developed cages display good water solubilities and can act as nanoreactors and light-harvesting systems to catalyze the difluoromethylation of quinoxalin-2(1H)-ones with sodium difluoromethanesulfinate under the irradiation of sunlight.Compared with eosin Y alone,this system displayed enhanced catalytic activity in catalyzing the difluoromethylation,which realizes the simulation of the photosynthesis process.展开更多
A novel iodonium-ylide compound 2 that appends a trifluoromethylthio （SCF3） group is disclosed as a new, shelf-stable electrophilic trifluoromethylation reagent. Unlike known shelf-stable electrophilic trifluorometh...A novel iodonium-ylide compound 2 that appends a trifluoromethylthio （SCF3） group is disclosed as a new, shelf-stable electrophilic trifluoromethylation reagent. Unlike known shelf-stable electrophilic trifluoromethylation reagents, 2 has a stable SCF3 group which is activated by appending iodonium ylide under copper catalysis via sul- fonium ylide to generate a cationic trifluoromethyl （CF3） species. Reagent 2 was found to be an efficient electro- philic trifluoromethylation reagent for a wide range of silyl enol ethers 3 under copper catalysis. Cyclic and acyclic a-trifiuoromethyl ketones 4 were obtained by reagent 2 in moderate to good yields. On the other hand, a difluoro- methylthio analogue 5 did not affect intermolecular transfer difluoromethylation to substrates. Instead, intramolecu- lar 1,4-migration proceeded similar to the Stevens rearrangement to provide 6 in 21% yield, independent of the presence of nucleophiles 3.展开更多
The direct excitation of dihydroquinazolinone(DHQ)anions by visible light has been demonstrated by photophysical experiments.The excited-state DHQ anion serves as both a potent reductant and a radical precursor in a r...The direct excitation of dihydroquinazolinone(DHQ)anions by visible light has been demonstrated by photophysical experiments.The excited-state DHQ anion serves as both a potent reductant and a radical precursor in a redox neutral radical cascade,circumventing the use of an external photoredox catalyst.Various gem-difluoroalkyl radicals(CF_(2)H and CF_(2)R)are produced from the excited-state DHQ anions,leading to the first example of intermolecular 1,2-difluoroalkylarylation(CF_(2)H-and CF_(2)R-arylation)of alkenes in overall redox-neutral manner.Similarly,1,2-difluoroalkylamination of styrenes has also been realized,offering a practical pathway for the preparation of diverseβ-CF_(2)H amines.This general and efficient strategy for the generation of CF_(2)H and CF_(2)R radicals exhibits great potential for applications in drug discovery.展开更多
文摘Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.
文摘A photocatalyst-free photoinduced radical difluoromethylation approach for the convenient synthesis of 3-CF_(2)H-coumarins from alkynoates by difluoromethyl phenoxathiinium salt(PT-CF_(2)H^(+)BF_(4)^(-))was developed.This transformation in-volves radical difluoromethylation/5-exo spirocyclization/ester migration rearrangement cascade process and features mild reaction conditions,broad substrate scope and good functional groups tolerance.Using this method,a wide range of alkynoates was successfully converted to desired 3-CF_(2)H-coumarins in moderate to good yields.
基金financial support from the National Natural Science Foundation of China(NSFC,No.21877067)Tsinghua-Peking Centre for Life Science。
文摘Herein,we describe a nickel-catalyzed reductive decarboxylative difluoromethylation reaction of alkenes using inexpensive and easy-to-handle difluoroacetic anhydride(DFAA)/pyridine N-oxide reagent system.A variety of C(sp^(3))-CF_(2)H containing compounds were prepared through a hydrodifluoromethylation process.Besides,various gem–difluoroalkenes bearing CF_(2)H group were synthesized via defluorinative reductive cross-coupling process from trifluoromethyl-substituted alkenes using this new reaction system.Difluoroacetic anhydride has been then extended to other common alkyl anhydrides,and the corresponding hydroalkylation and defluoroalkylation processes have been successfully achieved.This method features broad substrate scope,good functional group tolerance as well as high efficiency.
基金supported by the Science and Technology Foundation of Shenzhen, Shenzhen Science and Technology Innovation Committee (No. JCYJ20170818143001461)
文摘A facile and highly efficient approach for selective O-difluoromethylation of 1,3-diones by recently developed bench-stable S-(difluoromethyl)sulfonium salt was described.And a broad range of difluoromthyl enol ethers were readily accessed in good to excellent yields under mild reaction conditions.Mechanistic studies revealed that the O-difluoromethylation reaction proceeds mainly via a difluorocarbene pathway.
基金financial supported by Innovation Program of Shanghai Municipal Education Commission(No.201701070002E00037)supported by National Key Research Program of China(No.2017YFD0200505)the Fundamental Research Funds for the Central Universities。
文摘Deuteriodifluoromethyl(CF_(2)D)is a challenging and important functional group due to difficult deuterium incorporation and lack of effective precursor reagents.Herein,we report a bench-stable reagent,deuteriodifluoromethyl phosphine(DDFP)from cheap deuterium source for selectivity deuteriodifluoromethylation of azines with a high deuterium incorporation yield.The late-stage modification of complex molecules further confirmed the potential of this reagent for practical applications.We expect that our reagent to find applications in synthesis of isotope-labelled molecules of interests for drug-discovery and related ilucidation of mechanism of action.
基金sponsored by the Natural Science Foundation of China(Nos.22371126,21776139 and 22072067)the“Qing Lan Project”Young and Middle-aged Academic Leaders of Jiangsu Provincial Colleges and Universities,the Natural Science Foundation of Jiangsu Province(No.BK20161553)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Practical,undirected and selective catalytic functionalization of unactivated arenes remains a challenging problem in organic synthesis.We herein report a bioinspired L-cystine-derived ligand BCPOM/Fe-enabled innate C-H difluoromethylation of unactivated arenes as limiting reagents with stable and inexpensive BrCF_(2)CO_(2)Et as the difluoromethylation source in high efficiency.Notably,this method uses environmentally benign H_(2)O_(2) as the sole oxidant,and enables late-stage functionalization and exceptionally functional-group tolerance,even including oxidation-labile aldehyde,phenolic hydroxy,primary amine,and boronic acid groups,which is difficult to access by current means.
基金support by the National Natural Science Foundation of China(22101157)is gratefully acknowledgedWe are very grateful to Prof.Xiao Shen(Wuhan University,China)for helpful discussion.
文摘The pursuit of sustainable and environmentally benign synthetic methods continues to challenge organic chemists. Herein, we introduce a magnetoredox system for tri- and difluoromethylation of isocyanides and N-arylacrylamides using a rotating magnetic field and steel rods. This magnetoredox approach enables facile synthesis of functionalized phenanthridines and oxindoles without the need for catalysts and additives under mild conditions. Such a system potentially represents an attractive strategy for selective formation of bonds through multifaceted regulation of magnetic intensity, rotating frequency, and rod size.
基金support from the National Key Research and Development Program of China(2021YFC2101901)National Natural Science Foundation of China(22202060)+6 种基金the Funding plan of key scientific research projects in colleges and universities of Henan Province(23A150029)Doctoral Scientific Research Start-up Foundation from Henan University of Technology(2021BS080)the Project of Youth Backbone Teachers of Henan University of Technology(21421251,21420072)the Science and Technology Cooperation Foundation of Zhengzhou City(21ZZXTCX16)the Innovative Funds Plan of Henan University of Technology(2021ZKCJ08)the Science and Technology Foundation of Henan Province(232102230093)Natural Science Foundation of Henan Province(242300421616).
文摘Herein,we report a photo-induced,metal-/additive-free protocol for the difluoromethylation of N-heteroaromatics with[bis(difluoroacetoxy)iodo]benzene as the difluoromethylation reagent.The protocol affords difluoromethylated N-heteroaromatics in moderate to good yield(up to 91%).The transformation is compatible with a wide range of substrates and has good tolerance towards various functional groups.Moreover,the synthetic value of this method is further demonstrated by applications in gram-scale synthesis and the late-stage functionalization of biologically important molecules.
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Projrct supportted by the National Natural Science Foundation of China （Nos. 20772144, 20825209, 20832008） and the Chinese Academy of Sciences （Hundreds-Talent Program and Knowledge Innovation Program）.
文摘Difluoromethyltri（n-butyl）ammonium chloride 1 was found to be an effective difluorocarbene reagent for O-, S-, N-, C-difluoromethylation under basic conditions. It is particularly remarkable that, when only 1.2 equivalent of reagent 1 was used, the difluoromethylated products were obtained in moderate to excellent yields.
基金supported by the China Postdoctoral Science Foundation (2021M702516)the National Key R&D Program of China (2021YFA1500104)+1 种基金the National Natural Science Foundation of China (22031008)the Science Foundation of Wuhan(2020010601012192)。
文摘CF_(2)H-containing molecules play pivotal roles in diverse fields from medicinal chemistry to materials science. However, the application of existing CF_(2)H reagents as a source of CF_(2)H radical is limited by their reactivity and preparation. Herein, we develop a simple and general visible-light-catalyzed radical difluoromethylation reaction of alkenes, dienes, and heteroaromatics using commercially available, easy-to-handle, and low-cost difluoroacetic anhydride as the CF_(2)H reagent. This scalable protocol enables the convenient synthesis of a range of CF_(2)H-containing compounds under mild conditions, exhibiting a broad substrate scope and functional group tolerance. Potential applications are further demonstrated by gram-scale synthesis, sunlight experiments, derivatization experiments as well as the synthesis of bioactive molecules.
基金supported by the National Key Research and Development Program of China(2021YFF0701700)the National Natural Science Foundation of China(22271299,22261132514)+1 种基金the Natural Science Foundation of Shandong Province(ZR2021LFG006)the State Key Laboratory of Fluorine-Containing Functional Membrane Materials。
文摘The divergent reductive cross-coupling with an ambident electrophile is rare.Previously,we demonstrated a nickel-catalyzed reductive 2-pyridination of aryl iodides with difluoromethyl 2-pyridyl sulfone(2-Py SO_(2)CF_(2)H)via selective C(sp^(2))-S bond cleavage of the sulfone by using a phosphine ligand.In this communication,we report a novel nickel-catalyzed reductive coupling of aryl iodides and 2-Py SO_(2)CF_(2)H reagent,which constitutes a new method for aromatic difluoromethylation.The use of a tridentate terpyridine ligand is pivotal for the selective C(sp^(3))-S bond cleavage of the sulfone.This method employs readily available nickel catalyst and 2-Py SO_(2)CF_(2)H as the difluoromethylation reagent,providing a facile access to difluoromethylarenes under mild reaction conditions without pre-generation of arylmetal reagents.
基金Financial support from the National Natural Science Foundation of China(Nos.22101267,U1904212,U2004191 and 21803059)is gratefully appreciated.
文摘Visible-light induced direct C–H difluoromethylation of quinoxalinones with 2-((difluoromethyl)sulfonyl)benzo[d]thiazole has been developed for the first time.A broad range of quinoxalinones were well tolerated and reacted with difluorosulfone smoothly to give the corresponding products in moderate to good yields.Notably,no external photocatalyst or oxidant was required,which provides a practical and green protocol to access difluoromethylated quinoxalinones.Finally,the control experiments demonstrated a radical mechanism,and the density functional theory(DFT)calculations indicated the radicals were generated through the formation of an electron donoracceptor(EDA)complex.
基金The Nationa authors gratefully acknowledge the financial support from Natural Science Foundation of China （21625206, 21632009, 21372247, 21572258, 21572259, 21421002） and the Strategic Priority Research Program of the Chinese Academy of Sciences （XDB20000000） and the Syngenta Ph.D. Fellowship （Y. Gu and C. Lu）.
文摘Highly regiodivergent copper-catalyzed allylic/propargylic difluoromethylation reactions by employing different ligands are described. When 5,6-dimethyl-1,10-phenanthroline was used as the ligand, exclusively α-difluoromethylated products were obtained, while γ-selective difluoromethylated products were generated when N-heterocyclic carbene-SIPr was used as the ligand. Likewise, high α- vs. γ-selectivities were achieved in the presence of similar copper catalysts for the reactions of propargyl bromides. Moreover, a copper-catalyzed asymmetric allylic difluoromethylation reaction with moderate to good enantioselectivity by the use of chiral ligands was developed.
基金research was made possible by the generous support of the Rhine-Westphalia Technical University of Aachen(RWTH Aachen University)We also acknowledge the Alexander von Humboldt Foundation for support of K.R.(AvH research award).
文摘Difluoromethyl ethers are formed through mechanochemical reactions of alcohols with difluorocarbene in a mixer mill.The protocol could be applied to primary,secondary,and tertiary alcohols,yielding the corresponding products in excellent yields(up to 99%)after 1 h reaction time at room temperature.The transformations proceeded under solvent-free reaction conditions,followed by product purification by filtration,which drastically reduced the amount of waste generated during the process.
基金the financial support from the National Key Research and Development Program of China(No.2021YFF0701700)the National Natural Science Foundation of China(No.22061160465)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB0590000)the Research Grants Council of Hong Kong(NSFC/RGC Joint Research Scheme,No.N_CUHK403/20)the Chinese University of Hong Kong(Faculty of Science-Direct Grant for Research)for funding。
文摘The active Cu(Ⅰ)species Q^(+)[Cu^(Ⅰ)(CF_(2)CO_(2)Et)(Cl)]^(-)1a and Q^(+)[Cu^(Ⅰ)(CF_(2)CO_(2)Et)_(2)]^(-)1b(Q=Ph_(4)P),which played an important role in the copper mediated ethoxycarbonyl difluoromethylation of organic halides,have been isolated and characterized for the first time.Stoichiometric reaction showed complex 1b is much more reactive than 1a.Furthermore,while oxidative addition of complex 1b with aryl iodide resulted in the formation of the reductive elimination product without the observation of the Cu(Ⅲ)intermediate,the oxidative addition of iodoacetronitrile to 1b successfully generated Cu(Ⅲ)intermediates that reductively eliminate to give the products.Building on the stoichiometric reaction,a copper-catalyzed ethoxycarbonyl difluoromethylation of benzylic,allylic halides was developed.Additionally,it has been found that complex 1b serves as a powerful ethoxycarbonyl difluoromethylation reagent capable of ethoxycarbonyl difluoromethylating a variety of electrophiles including(hetero)aryl electrophiles,alkyl electrophiles and acid chloride,disulfide.Moreover,the oxidative ethoxycarbonyl difluoromethylation of complex 1b with various lithium n–butyl(hetero)aryl boronic acid pinacol esters has been achieved in the presence of an oxidant.
基金The Shanghai Pujiang Program(No09PJ1400800)the Fundamental Research Funds for the Central Universities and the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry
文摘Stereoselective approach for preparation ofα-difluoromethylα-propargylamines has been developed.1,2-Addition of lithium acetylides to diverse chiral difluoromethylated（S）-N-tert-butanesulfinyl ketimines by using Ti（O^iPr）_4 as catalyst and THF as solvent afforded N-tert-butanesulfinamides in good to excellent yields（51-93%） and good diastereoselectivities（dr.85：15 to 93：7）.The N-tert -butanesulfinyl group can be readily cleaved under mild acidic condition（4 mol/L HCl in dioxane） to provide the correspondingα-difiuoromethylα-propargylamine in excellent yields（90-95%）.
基金National Natural Science Foundation of China(Nos.22101267,21672192,21803059,U2004191,U1904212 and 21801063)for financial support.
文摘Two discrete octahedral metallo-supramolecular cages were designed and constructed by using truxene-based pyridine L with enPd(NO_(3))_(2)or enPt(NO_(3))_(2),followed by detailed NMR,MS,UV absorption,and fluorescence spectroscopy.Owing to the determined cavity size and excellent optical performance of cages,the resulting supramolecular cages were confirmed to be the light-harvesting system based on Foster resonance energy-transfer(FRET).The developed cages display good water solubilities and can act as nanoreactors and light-harvesting systems to catalyze the difluoromethylation of quinoxalin-2(1H)-ones with sodium difluoromethanesulfinate under the irradiation of sunlight.Compared with eosin Y alone,this system displayed enhanced catalytic activity in catalyzing the difluoromethylation,which realizes the simulation of the photosynthesis process.
文摘A novel iodonium-ylide compound 2 that appends a trifluoromethylthio （SCF3） group is disclosed as a new, shelf-stable electrophilic trifluoromethylation reagent. Unlike known shelf-stable electrophilic trifluoromethylation reagents, 2 has a stable SCF3 group which is activated by appending iodonium ylide under copper catalysis via sul- fonium ylide to generate a cationic trifluoromethyl （CF3） species. Reagent 2 was found to be an efficient electro- philic trifluoromethylation reagent for a wide range of silyl enol ethers 3 under copper catalysis. Cyclic and acyclic a-trifiuoromethyl ketones 4 were obtained by reagent 2 in moderate to good yields. On the other hand, a difluoro- methylthio analogue 5 did not affect intermolecular transfer difluoromethylation to substrates. Instead, intramolecu- lar 1,4-migration proceeded similar to the Stevens rearrangement to provide 6 in 21% yield, independent of the presence of nucleophiles 3.
基金the National Natural Science Foundation of China(grant nos.22101176 and 22137003).
文摘The direct excitation of dihydroquinazolinone(DHQ)anions by visible light has been demonstrated by photophysical experiments.The excited-state DHQ anion serves as both a potent reductant and a radical precursor in a redox neutral radical cascade,circumventing the use of an external photoredox catalyst.Various gem-difluoroalkyl radicals(CF_(2)H and CF_(2)R)are produced from the excited-state DHQ anions,leading to the first example of intermolecular 1,2-difluoroalkylarylation(CF_(2)H-and CF_(2)R-arylation)of alkenes in overall redox-neutral manner.Similarly,1,2-difluoroalkylamination of styrenes has also been realized,offering a practical pathway for the preparation of diverseβ-CF_(2)H amines.This general and efficient strategy for the generation of CF_(2)H and CF_(2)R radicals exhibits great potential for applications in drug discovery.
