A library of novel 3-aryl isoindolinone derivatives with aromatic amino acid derivative fragments was designed and synthesized. Two synthetic routes were employed to construct 3-aryl isoindolinone ring system for diff...A library of novel 3-aryl isoindolinone derivatives with aromatic amino acid derivative fragments was designed and synthesized. Two synthetic routes were employed to construct 3-aryl isoindolinone ring system for different amino acid derivatives.展开更多
A series of 3-acyl-substituted isoindolinone derivatives were synthesized in a one-pot manner via the reaction of o-bromobenzaldehydes,isocyanides,and carboxylic acids in the presence of palladium catalyst and base. T...A series of 3-acyl-substituted isoindolinone derivatives were synthesized in a one-pot manner via the reaction of o-bromobenzaldehydes,isocyanides,and carboxylic acids in the presence of palladium catalyst and base. The reaction employing easily available starting materials features simple operation and high efficiency. The mechanistic study showed that the reaction might undergo 1) Pd-catalyzed [3+2] cyclization of o-bromobenzaldehyde with isocyanide and the re-insertion of another molecule of isocyanide,2) addition of carboxylic acid to in situ formed ketenimine followed by a rearrangement relay to give 3,3-diacyl-substituted isoindolinone derivative. Further transformations of the obtained products through decarbonylation could also be realized.展开更多
The isoindolinone and biaryl scaffolds are prevalent in natural products and drug molecules,which have showed broad and interesting biological activities.The efficient construction of such hybridized molecules and bio...The isoindolinone and biaryl scaffolds are prevalent in natural products and drug molecules,which have showed broad and interesting biological activities.The efficient construction of such hybridized molecules and biological evaluation are of great interest to medicinal chemistry community.In this communication,we report an efficient BrΦnsted acid-promoted C(sp^3)-H functionalization approach that enables the rapid construction of biologically important isoindolinone/[1,2,4]triazolo[1,5-a]pyrimidine hybrids from 5-methyl-7-(2,4,6-trimethoxyphenyl)-[1,2,4]triazolo[1,5-a]pyrimidine,2-formylbenzoic acid and various anilines.The title compounds were generated in high to excellent yields(up to 96%)regardless of the electronic nature and steric effects of the substituents.In this reaction,an isoindolinone scaffold,one C-C single bond,and two C-N bonds were formed simultaneously with high atom economy.In this work,we have envisioned that the methyl group linked to the electron-deficient Nheterocycles could be used as a new synthetic handle for late-state diversification and may have broad applications in the field of organic and medicinal chemistry.Besides,the title compounds have exhibited promising activity against the SKP2-CKS1 interaction.展开更多
A H_(4)SiW_(12)O_(40)-catalyzed three-component tandem reaction of 2-acylbenzoic acids,primary amines and phosphine oxides to form 3,3-disubstituted isoindolinones was developed.By employing A H_(4)SiW_(12)O_(40)as th...A H_(4)SiW_(12)O_(40)-catalyzed three-component tandem reaction of 2-acylbenzoic acids,primary amines and phosphine oxides to form 3,3-disubstituted isoindolinones was developed.By employing A H_(4)SiW_(12)O_(40)as the catalyst and dimethyl carbonate(DMC)as the solvent,a diverse range of 2-acylbenzoic acid derivatives and primary amines worked well to give the C3-phosphinoyl-functionalized 3,3-disubstituted isoindolinones with the yield range of 61%-87%.Advantages of this transformation include green catalyst and solvent,available starting materials,broad substrate scope,high efficiency and operational simplicity with water as the sole by-product.The strategy achieved an efficient and green molecular fragment assembly to access isoindolinones,which would provide opportunities for the synthesis of potential biologically active molecules in a green manner.展开更多
Under photocatalytic reductive conditions,trifluoromethyl radical addition onto an ynamide followed by cyclization on a benzoyl moiety produces diverse isoindolinone platforms with good yields.The selectivity of the r...Under photocatalytic reductive conditions,trifluoromethyl radical addition onto an ynamide followed by cyclization on a benzoyl moiety produces diverse isoindolinone platforms with good yields.The selectivity of the radical cyclization,N-benzoyl vs.N-benzyl as radical acceptor and the E/Z ratio of isomers have been rationalized by modeling.展开更多
A mild and efficient oxidative synthesis of isoindolinones has been realized by Rh(III)‐catalyzed C?H activation of benzamides and[4+1]coupling with propargyl alcohols.This coupling system proceeds with broad substra...A mild and efficient oxidative synthesis of isoindolinones has been realized by Rh(III)‐catalyzed C?H activation of benzamides and[4+1]coupling with propargyl alcohols.This coupling system proceeds with broad substrate scope and mild conditions and provides a new approach to access the useful skeleton ofγ‐lactams with a stereogenic center.展开更多
Herein,we report a condition-controlled divergent synthesis of spiro indene-2,1'-isoindolinones and spiro isochroman-3,1'-isoindolinones through cobalt-catalyzed formal[4+1]and[4+1+1]spirocyclization of aromat...Herein,we report a condition-controlled divergent synthesis of spiro indene-2,1'-isoindolinones and spiro isochroman-3,1'-isoindolinones through cobalt-catalyzed formal[4+1]and[4+1+1]spirocyclization of aromatic amides with 2-diazo-1H-indene-1,3(2H)-dione.When the reaction is carried out under air in ethyl acetate,spiro indene-2,1'-isoindolinones are formed through Co(II)-catalyzed C—H/N—H[4+1]spirocyclization.When the reaction is run under O2 in CH3CN,on the other hand,spiro isochroman-3,1'-isoindolinones are generated through Baeyer-Villiger oxidation of the in situ formed spiro indene-2,1'-isoindolinones with O2 as a cheaper and environmental-friendly oxygen source.In general,these protocols have advantages such as using non-precious and earth-abundant metal catalyst,no extra additive,high efficiency and regioselectivity.A gram-scale synthesis and the removal of the directing group further highlight its utility.展开更多
基金Supported by the National Natural Science Foundation of China（No.81072526） and the Fund of the Department of Science and Technology of Jilin Province of China（No.20106039）.
文摘A library of novel 3-aryl isoindolinone derivatives with aromatic amino acid derivative fragments was designed and synthesized. Two synthetic routes were employed to construct 3-aryl isoindolinone ring system for different amino acid derivatives.
基金the National Natural Science Foundation of China(Nos.21772138 and 21672157)the Natural Science Foundation of Jiangsu Province(BK20221356)PAPD。
文摘A series of 3-acyl-substituted isoindolinone derivatives were synthesized in a one-pot manner via the reaction of o-bromobenzaldehydes,isocyanides,and carboxylic acids in the presence of palladium catalyst and base. The reaction employing easily available starting materials features simple operation and high efficiency. The mechanistic study showed that the reaction might undergo 1) Pd-catalyzed [3+2] cyclization of o-bromobenzaldehyde with isocyanide and the re-insertion of another molecule of isocyanide,2) addition of carboxylic acid to in situ formed ketenimine followed by a rearrangement relay to give 3,3-diacyl-substituted isoindolinone derivative. Further transformations of the obtained products through decarbonylation could also be realized.
基金supported by the National Natural Science Foundation of China(Nos.81773562 and 81703326)China Postdoctoral Science Foundation(Nos.2018M630840 and 2019T120641)Scientific Program of Henan Province(No.182102310123)。
文摘The isoindolinone and biaryl scaffolds are prevalent in natural products and drug molecules,which have showed broad and interesting biological activities.The efficient construction of such hybridized molecules and biological evaluation are of great interest to medicinal chemistry community.In this communication,we report an efficient BrΦnsted acid-promoted C(sp^3)-H functionalization approach that enables the rapid construction of biologically important isoindolinone/[1,2,4]triazolo[1,5-a]pyrimidine hybrids from 5-methyl-7-(2,4,6-trimethoxyphenyl)-[1,2,4]triazolo[1,5-a]pyrimidine,2-formylbenzoic acid and various anilines.The title compounds were generated in high to excellent yields(up to 96%)regardless of the electronic nature and steric effects of the substituents.In this reaction,an isoindolinone scaffold,one C-C single bond,and two C-N bonds were formed simultaneously with high atom economy.In this work,we have envisioned that the methyl group linked to the electron-deficient Nheterocycles could be used as a new synthetic handle for late-state diversification and may have broad applications in the field of organic and medicinal chemistry.Besides,the title compounds have exhibited promising activity against the SKP2-CKS1 interaction.
基金the National Natural Science Foundation of China(No.22001034)Jiangxi Provincial Natural Science Foundation(No.20212BAB213001).
文摘A H_(4)SiW_(12)O_(40)-catalyzed three-component tandem reaction of 2-acylbenzoic acids,primary amines and phosphine oxides to form 3,3-disubstituted isoindolinones was developed.By employing A H_(4)SiW_(12)O_(40)as the catalyst and dimethyl carbonate(DMC)as the solvent,a diverse range of 2-acylbenzoic acid derivatives and primary amines worked well to give the C3-phosphinoyl-functionalized 3,3-disubstituted isoindolinones with the yield range of 61%-87%.Advantages of this transformation include green catalyst and solvent,available starting materials,broad substrate scope,high efficiency and operational simplicity with water as the sole by-product.The strategy achieved an efficient and green molecular fragment assembly to access isoindolinones,which would provide opportunities for the synthesis of potential biologically active molecules in a green manner.
文摘Under photocatalytic reductive conditions,trifluoromethyl radical addition onto an ynamide followed by cyclization on a benzoyl moiety produces diverse isoindolinone platforms with good yields.The selectivity of the radical cyclization,N-benzoyl vs.N-benzyl as radical acceptor and the E/Z ratio of isomers have been rationalized by modeling.
基金supported by the Dalian Institute of Chemical Physics,Chinese Academy of Sciencesthe National Natural Science Foundation of China (21525208,21472186)~~
文摘A mild and efficient oxidative synthesis of isoindolinones has been realized by Rh(III)‐catalyzed C?H activation of benzamides and[4+1]coupling with propargyl alcohols.This coupling system proceeds with broad substrate scope and mild conditions and provides a new approach to access the useful skeleton ofγ‐lactams with a stereogenic center.
基金the National Natural Science Foundation of China(22101075,U2004189)Central Plains Science and Technology Innovation Leader Project(224200510009)+1 种基金Postdoctoral Research Grant in Henan Province(202103085)Henan Key Laboratory of Organic Functional Molecules and Drug Innovation,and 111 Project(D17007)for financial support.
文摘Herein,we report a condition-controlled divergent synthesis of spiro indene-2,1'-isoindolinones and spiro isochroman-3,1'-isoindolinones through cobalt-catalyzed formal[4+1]and[4+1+1]spirocyclization of aromatic amides with 2-diazo-1H-indene-1,3(2H)-dione.When the reaction is carried out under air in ethyl acetate,spiro indene-2,1'-isoindolinones are formed through Co(II)-catalyzed C—H/N—H[4+1]spirocyclization.When the reaction is run under O2 in CH3CN,on the other hand,spiro isochroman-3,1'-isoindolinones are generated through Baeyer-Villiger oxidation of the in situ formed spiro indene-2,1'-isoindolinones with O2 as a cheaper and environmental-friendly oxygen source.In general,these protocols have advantages such as using non-precious and earth-abundant metal catalyst,no extra additive,high efficiency and regioselectivity.A gram-scale synthesis and the removal of the directing group further highlight its utility.
