Catalytic asymmetric dearomatization(CADA)of phenols has emerged as a powerful strategy for constructing stereochemically complicated architectures from planar aromatic feedstocks.However,the development of novel cata...Catalytic asymmetric dearomatization(CADA)of phenols has emerged as a powerful strategy for constructing stereochemically complicated architectures from planar aromatic feedstocks.However,the development of novel catalysts for highly enantioselective phenolic oxidative dearomatization continues to be a time-and resource-intensive endeavor,attributable mainly to the paucity of a reliable predictive catalyst design strategy.In this study,we systematically compiled a dataset of 847 literaturereported asymmetric phenolic dearomatization by hypervalent iodine(III)catalysts(HVI-CADA dataset),a unique type of catalyst that is gaining increasing attention owing to their ecofriendly features.Leveraging this reaction dataset,we established a machine learning predictive model to predict enantioselectivity.The XGBoost algorithm exhibited the optimal performance,with a root-mean-square error of 0.26(kcal/mol)and an R^(2)of 0.84.This established model can effectively guide the selection of the optimal catalyst and additives in out-of-sample tests.Subsequent independent experiments were conducted to validate the results obtained from the model predictions.We anticipate that our current work will facilitate further design,optimization,and development of novel chiral hypervalent iodine catalysts for new asymmetric phenolic dearomatization reactions.展开更多
Hypervalent iodine(Ⅲ)reagents have been vastly used in many useful organic transformations.In this review article,we highlight the strategies that used the common hypervalent iodine(Ⅲ)reagents as oxidants to synthes...Hypervalent iodine(Ⅲ)reagents have been vastly used in many useful organic transformations.In this review article,we highlight the strategies that used the common hypervalent iodine(Ⅲ)reagents as oxidants to synthesize the heterocyclic compounds,based on the patterns of bond formation during the construction of the heterocyclic backbones.展开更多
An effective and environmentally benign benzylic oxidation for transition of alkylarenes into the corresponding carbonyl compounds was reported. Alkylarenes were mixed and stirred with potassium bromide, m-chloroperbe...An effective and environmentally benign benzylic oxidation for transition of alkylarenes into the corresponding carbonyl compounds was reported. Alkylarenes were mixed and stirred with potassium bromide, m-chloroperbenzoic acid and a catalytic amount of iodobenzene in water at 60 ℃ for several hours, a series of the corresponding carbonyl compounds was obtained in moderate to good yields. In the reaction, iodobenzene was first oxidized by m-chloroperbenzoic acid into the hypervalent iodine intermediate which then reacted with potassium bromide to form the key radical initiator for the benzylic oxidation.展开更多
An intermolecular two C-C bond formation procedure for the synthesis of carbocycles mediated by hyperva-lent iodine(III)reagents was developed.This metal free protocol provided a new approach for the synthesis of use-...An intermolecular two C-C bond formation procedure for the synthesis of carbocycles mediated by hyperva-lent iodine(III)reagents was developed.This metal free protocol provided a new approach for the synthesis of use-ful substituted 1-amino-2-naphthoic acid derivatives via benzannulation reactions.Various N-unsubstituted and N-alkyl substituted aromatic enamines with terminal alkynes and non-terminal alkynes can be converted into corre-sponding 1-amino-2-naphthoic acid derivatives under mild reaction conditions.When meta-substituted phenyl enamines were employed in the reaction,two cyclization paths were detected in the reaction and ortho-cyclization products were the only or major products.Good functional group tolerance,readily available material and high atom utilization efficiency make this method a potential procedure which may find broad application in organic synthesis.展开更多
β-Difluorinated alkyl halides are of significant value in the modular synthesis of gem-difluorinated molecules.An exclusive 1,2-halo migratory gem-difluorination of vinyl halides with in situ-generated PhIF_(2)·...β-Difluorinated alkyl halides are of significant value in the modular synthesis of gem-difluorinated molecules.An exclusive 1,2-halo migratory gem-difluorination of vinyl halides with in situ-generated PhIF_(2)·HF is described.This protocol provides a general and practical approach towards a wide variety ofβ-difluorinated alkyl bromides.Bothα-andβ-bromoalkyl alkenes are suitable substrates,leading to two distinct types of products.The extension of this protocol to vinyl chloride and iodide are also feasible.The synthetic versatility of this method has been highlighted by the late-stage modification of complex small molecules and further transformations of theβ-difluorinated alkyl halides to valuable CF_(2)-containing compounds.展开更多
An efficient and facile method for C-H amination of quinoxalinones with heteroaromatic amines under metal-free conditions has been described.In the presence of hypervalent PIDA reagent,the desired products with variou...An efficient and facile method for C-H amination of quinoxalinones with heteroaromatic amines under metal-free conditions has been described.In the presence of hypervalent PIDA reagent,the desired products with various groups were obtained with moderate to high yields.展开更多
Rh(Ⅲ)-catalyzed, chelation-assisted oxidative C-H imidation of arenes with N-H imide have been realized using PhI(OAc)2 as an oxidant. This transformation exhibits a broad substrate scope and tolerates various functi...Rh(Ⅲ)-catalyzed, chelation-assisted oxidative C-H imidation of arenes with N-H imide have been realized using PhI(OAc)2 as an oxidant. This transformation exhibits a broad substrate scope and tolerates various functional groups. The reaction proceeded via in situ generation of an iodine(Ⅲ) imido. DFT calculations suggest that this oxidative imidaton system proceeds via a Rh(Ⅲ)-Rh(Ⅴ)-Rh(Ⅲ) pathway.展开更多
A formal[3+3]annulation of 3-aminopyrazoles with cinnamaldehydes or cinnamyl alcohols mediated by NH_(4)SCN has been developed.This protocol provides a practical route to construct 5-arylated pyrazolo[1,5-a]pyrimidine...A formal[3+3]annulation of 3-aminopyrazoles with cinnamaldehydes or cinnamyl alcohols mediated by NH_(4)SCN has been developed.This protocol provides a practical route to construct 5-arylated pyrazolo[1,5-a]pyrimidines with high functional group tolerance.The use of NH_(4)SCN as the cyanide anion surrogate allows the transient generation of cyanohydrin,which shifts the reactive center within cinnamaldehydes from formyl group to alkene group to realize an opposite regiocontrol comparing with previous reports.展开更多
C(sp2)-H amination represents an attractive approach for the synthesis of enamines,which is intrinsically associated with the challenge of controlling of stereochemistry and primarily relying on transition-metal catal...C(sp2)-H amination represents an attractive approach for the synthesis of enamines,which is intrinsically associated with the challenge of controlling of stereochemistry and primarily relying on transition-metal catalysis.Herein,a metal-free C(sp2)-H amination ofα-substituted styrenes has been achieved,leading to stereodivergent formation of both E-and Z-enamines in 50%–97%yield under mild conditions by using PhI(OAc)2 as a green oxidant and ortho-phenylenediamines as nitrogen source.Interestingly,the Z/E selectivity can be controlled readily by switching the reaction medium.E-isomers were formed preferentially in THF,whereas n-hexane favored the formation of Z-isomers.Preliminary mechanistic studies suggested that in situ formed ortho-benzoquinone diimides are the key intermediates,and there is a correlation between solvent polarity and stereoselectivity.This study enriches the chemical repertoire of ortho-benzoquinone diimides particularly with respect to sustainable amination.展开更多
Atom-and step-economy in IBX assisted diversity-oriented synthesis is achieved with a versatile AQ auxiliary α-amino acid analogs offering rapid access to polycyclic spiro-quinolines featuring a quaternary stereocent...Atom-and step-economy in IBX assisted diversity-oriented synthesis is achieved with a versatile AQ auxiliary α-amino acid analogs offering rapid access to polycyclic spiro-quinolines featuring a quaternary stereocenter in 20%–91% yields under mild conditions via 7,8-dearomatization of quinolines. Free of a preinstalled activation group is highlight of this intramolecular oxidation spiroannulation tandem reaction. This type of N-heterospirocycles, traditionally difficult to access, may open the door to a potentially interest scaffold for synthetic and medicinal chemistry.展开更多
Reductive iodonio-Claisen rearrangement （RICR） involving 23-iodanes and allyl or substituted-allyl silanes in fluoroalcohols, such as 1,1,1,3,3,3-hexafluoroi- sopropanol （HFIP） and 2,2,2-trifluoroethanol （TFE）, ...Reductive iodonio-Claisen rearrangement （RICR） involving 23-iodanes and allyl or substituted-allyl silanes in fluoroalcohols, such as 1,1,1,3,3,3-hexafluoroi- sopropanol （HFIP） and 2,2,2-trifluoroethanol （TFE）, was studied for the synthesis of complex ortho-allyl or substituted-allyl iodoarenes. In comparison to the pre- viously reported condition involving boron trifluoride diethyl etherate, the RICR mediated by fluoroalcohols was found to proceed more effectively. The resulting complex ortho-allyl iodoarenes are useful synthetic intermediates and can be readily converted to various heterocyclic compounds.展开更多
We report a 2-iodoxybenzoic acid(IBX)-mediated intarmolecular oxidative spiro-fused tandem cyclization reaction of tryptophan analogs bearing an N-arylamides side-chain to rapidly afford polycyclic spiroindolines feat...We report a 2-iodoxybenzoic acid(IBX)-mediated intarmolecular oxidative spiro-fused tandem cyclization reaction of tryptophan analogs bearing an N-arylamides side-chain to rapidly afford polycyclic spiroindolines featuring multiple stereocenters including a quaternary stereocenters under mild reaction conditions.Among them,a novelty azaphosphol idine-containing spiroindoline compound is synthesized for the first time.It may open the door to azaphos pholidine-containing spiroindoline compound of potential interest in synthetic and medicinal chemistry.A plausible mechanism is proposed.展开更多
An efficient method was developed for chlorination of aromatic compounds with electron-donating groups using iodobenzene as the catalyst and m-chloroperbenzoic acid as the terminal oxidant in the presence of 4-methylb...An efficient method was developed for chlorination of aromatic compounds with electron-donating groups using iodobenzene as the catalyst and m-chloroperbenzoic acid as the terminal oxidant in the presence of 4-methylbenzenesulfonic acid in THF at room temperature for 24 h,and a series of the monochlorinated compounds was obtained in good yields.In this protocol,the catalyst iodobenzene was first oxidized into the hypervalent iodine intermediate,which then treated with lithium chloride and finally reacted with aromatic compounds to form the chlorinated compounds.展开更多
Umpolung is a fundamental concept in organic chemistry, which provides an alternative strategy for the synthesis of target compounds which were not easily accessible by conventional methods. Herein, a mild and efficie...Umpolung is a fundamental concept in organic chemistry, which provides an alternative strategy for the synthesis of target compounds which were not easily accessible by conventional methods. Herein, a mild and efficient PhI(OAc)_2-promoted umpolung acetoxylation reactions of enamides was developed for the synthesis of α-acetoxy ketones. The reaction tolerates a wide range of functional groups and affords α-acetoxy ketones in good to excellent yields. PhI(OAc)_2 serves as a source of acetoxy in the reaction.展开更多
The polysubstituted and spirocyclic cyclobutanes were efficiently constructed by the utilization of a novel skeletal contraction strategy which only took one-step synthesis from the readily accessible pyrrolidines.The...The polysubstituted and spirocyclic cyclobutanes were efficiently constructed by the utilization of a novel skeletal contraction strategy which only took one-step synthesis from the readily accessible pyrrolidines.The mechanistic studies indicated that a key intermediate N-aminated pyrrolidine was formed initially and subsequent extrusion of a nitrogen via a radical pathway completed the transformation.This practical methodology was further highlighted by the concise,formal synthesis of the cytotoxic natural product piperarborenine B.展开更多
基金supported by the Ministry of Science and Technology of China(grant no.2021YFF0701700)the National Natural Science Foundation of China(grant nos.22122104,22193012,and 21933004)+1 种基金the CAS Project for Young Scientists in Basic Research(grant nos.YSBR-052 and YSBR-095)the Strategic Priority Research Program of the Chinese Academy of Sciences(grant no.XDB0590000).
文摘Catalytic asymmetric dearomatization(CADA)of phenols has emerged as a powerful strategy for constructing stereochemically complicated architectures from planar aromatic feedstocks.However,the development of novel catalysts for highly enantioselective phenolic oxidative dearomatization continues to be a time-and resource-intensive endeavor,attributable mainly to the paucity of a reliable predictive catalyst design strategy.In this study,we systematically compiled a dataset of 847 literaturereported asymmetric phenolic dearomatization by hypervalent iodine(III)catalysts(HVI-CADA dataset),a unique type of catalyst that is gaining increasing attention owing to their ecofriendly features.Leveraging this reaction dataset,we established a machine learning predictive model to predict enantioselectivity.The XGBoost algorithm exhibited the optimal performance,with a root-mean-square error of 0.26(kcal/mol)and an R^(2)of 0.84.This established model can effectively guide the selection of the optimal catalyst and additives in out-of-sample tests.Subsequent independent experiments were conducted to validate the results obtained from the model predictions.We anticipate that our current work will facilitate further design,optimization,and development of novel chiral hypervalent iodine catalysts for new asymmetric phenolic dearomatization reactions.
基金the National Natural Science Foundation of China(21072148)Foundation(B)for Peiyang Scholar-Young Core Faculty of Tianjin University(2013XR-0144)the Innovation Foundation of Tianjin University(2013XJ-0005)for financial support
文摘Hypervalent iodine(Ⅲ)reagents have been vastly used in many useful organic transformations.In this review article,we highlight the strategies that used the common hypervalent iodine(Ⅲ)reagents as oxidants to synthesize the heterocyclic compounds,based on the patterns of bond formation during the construction of the heterocyclic backbones.
基金support from the Natural Science Foundation of China (No. 21072176)the Zhejiang ProvinceNatural Science Foundation of China (No. Y4100231)
文摘An effective and environmentally benign benzylic oxidation for transition of alkylarenes into the corresponding carbonyl compounds was reported. Alkylarenes were mixed and stirred with potassium bromide, m-chloroperbenzoic acid and a catalytic amount of iodobenzene in water at 60 ℃ for several hours, a series of the corresponding carbonyl compounds was obtained in moderate to good yields. In the reaction, iodobenzene was first oxidized by m-chloroperbenzoic acid into the hypervalent iodine intermediate which then reacted with potassium bromide to form the key radical initiator for the benzylic oxidation.
基金support of this work by Baoji University of Arts and Sciences(No.ZK15046).
文摘An intermolecular two C-C bond formation procedure for the synthesis of carbocycles mediated by hyperva-lent iodine(III)reagents was developed.This metal free protocol provided a new approach for the synthesis of use-ful substituted 1-amino-2-naphthoic acid derivatives via benzannulation reactions.Various N-unsubstituted and N-alkyl substituted aromatic enamines with terminal alkynes and non-terminal alkynes can be converted into corre-sponding 1-amino-2-naphthoic acid derivatives under mild reaction conditions.When meta-substituted phenyl enamines were employed in the reaction,two cyclization paths were detected in the reaction and ortho-cyclization products were the only or major products.Good functional group tolerance,readily available material and high atom utilization efficiency make this method a potential procedure which may find broad application in organic synthesis.
基金This work was supported by the National Natural Science Foundation of China(21961047,21901266,21971261,22022114).
文摘β-Difluorinated alkyl halides are of significant value in the modular synthesis of gem-difluorinated molecules.An exclusive 1,2-halo migratory gem-difluorination of vinyl halides with in situ-generated PhIF_(2)·HF is described.This protocol provides a general and practical approach towards a wide variety ofβ-difluorinated alkyl bromides.Bothα-andβ-bromoalkyl alkenes are suitable substrates,leading to two distinct types of products.The extension of this protocol to vinyl chloride and iodide are also feasible.The synthetic versatility of this method has been highlighted by the late-stage modification of complex small molecules and further transformations of theβ-difluorinated alkyl halides to valuable CF_(2)-containing compounds.
基金supported by the National Natural Science Foundation of China (No.21772107)Shandong Province Key Research and Development Plan (No.2019GSF108017)。
文摘An efficient and facile method for C-H amination of quinoxalinones with heteroaromatic amines under metal-free conditions has been described.In the presence of hypervalent PIDA reagent,the desired products with various groups were obtained with moderate to high yields.
文摘Rh(Ⅲ)-catalyzed, chelation-assisted oxidative C-H imidation of arenes with N-H imide have been realized using PhI(OAc)2 as an oxidant. This transformation exhibits a broad substrate scope and tolerates various functional groups. The reaction proceeded via in situ generation of an iodine(Ⅲ) imido. DFT calculations suggest that this oxidative imidaton system proceeds via a Rh(Ⅲ)-Rh(Ⅴ)-Rh(Ⅲ) pathway.
文摘A formal[3+3]annulation of 3-aminopyrazoles with cinnamaldehydes or cinnamyl alcohols mediated by NH_(4)SCN has been developed.This protocol provides a practical route to construct 5-arylated pyrazolo[1,5-a]pyrimidines with high functional group tolerance.The use of NH_(4)SCN as the cyanide anion surrogate allows the transient generation of cyanohydrin,which shifts the reactive center within cinnamaldehydes from formyl group to alkene group to realize an opposite regiocontrol comparing with previous reports.
基金supported by the National Natural Science Foundation of China(No.22001085)Shandong Provincial Natural Science Foundation(No.ZR2021QB148)+1 种基金Fundamental Research Funds for the Central Universities(No.HUST:2023JCYJ001)Research Institute of Zhejiang Sci-Tech University in Longgang(No.LGYJY2021013)for financial support。
文摘C(sp2)-H amination represents an attractive approach for the synthesis of enamines,which is intrinsically associated with the challenge of controlling of stereochemistry and primarily relying on transition-metal catalysis.Herein,a metal-free C(sp2)-H amination ofα-substituted styrenes has been achieved,leading to stereodivergent formation of both E-and Z-enamines in 50%–97%yield under mild conditions by using PhI(OAc)2 as a green oxidant and ortho-phenylenediamines as nitrogen source.Interestingly,the Z/E selectivity can be controlled readily by switching the reaction medium.E-isomers were formed preferentially in THF,whereas n-hexane favored the formation of Z-isomers.Preliminary mechanistic studies suggested that in situ formed ortho-benzoquinone diimides are the key intermediates,and there is a correlation between solvent polarity and stereoselectivity.This study enriches the chemical repertoire of ortho-benzoquinone diimides particularly with respect to sustainable amination.
基金the National Natural Science Foundation of China (Nos. 22101074, 21877206, and 21772032)the 111 Project (No. D17007)+2 种基金Excellent Youth Foundation of Henan Scientific Committee (No. 222300420012)China Postdoctoral Science Foundation (No. 2019M660173)the Natural Science Foundation of Henan Province (No. 202300410233)。
文摘Atom-and step-economy in IBX assisted diversity-oriented synthesis is achieved with a versatile AQ auxiliary α-amino acid analogs offering rapid access to polycyclic spiro-quinolines featuring a quaternary stereocenter in 20%–91% yields under mild conditions via 7,8-dearomatization of quinolines. Free of a preinstalled activation group is highlight of this intramolecular oxidation spiroannulation tandem reaction. This type of N-heterospirocycles, traditionally difficult to access, may open the door to a potentially interest scaffold for synthetic and medicinal chemistry.
文摘Reductive iodonio-Claisen rearrangement （RICR） involving 23-iodanes and allyl or substituted-allyl silanes in fluoroalcohols, such as 1,1,1,3,3,3-hexafluoroi- sopropanol （HFIP） and 2,2,2-trifluoroethanol （TFE）, was studied for the synthesis of complex ortho-allyl or substituted-allyl iodoarenes. In comparison to the pre- viously reported condition involving boron trifluoride diethyl etherate, the RICR mediated by fluoroalcohols was found to proceed more effectively. The resulting complex ortho-allyl iodoarenes are useful synthetic intermediates and can be readily converted to various heterocyclic compounds.
基金the National Natural Science Foundation of China(Nos.U1604285,21772032 and 21702051)Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT)of Ministry of Education of China(No.IRT1061)+3 种基金the 111 Project(No.D17007)Henan Provincial Natural Science Foundation(No.162300410180)Key Project of Henan Educational Committee(No.18A150009)Program for Innovative Research Team of Science and Technology in the University of Henan Province(No.18IRTSTHN004)。
文摘We report a 2-iodoxybenzoic acid(IBX)-mediated intarmolecular oxidative spiro-fused tandem cyclization reaction of tryptophan analogs bearing an N-arylamides side-chain to rapidly afford polycyclic spiroindolines featuring multiple stereocenters including a quaternary stereocenters under mild reaction conditions.Among them,a novelty azaphosphol idine-containing spiroindoline compound is synthesized for the first time.It may open the door to azaphos pholidine-containing spiroindoline compound of potential interest in synthetic and medicinal chemistry.A plausible mechanism is proposed.
基金Financial support from the Natural Science Foundation of China (No.21072176)
文摘An efficient method was developed for chlorination of aromatic compounds with electron-donating groups using iodobenzene as the catalyst and m-chloroperbenzoic acid as the terminal oxidant in the presence of 4-methylbenzenesulfonic acid in THF at room temperature for 24 h,and a series of the monochlorinated compounds was obtained in good yields.In this protocol,the catalyst iodobenzene was first oxidized into the hypervalent iodine intermediate,which then treated with lithium chloride and finally reacted with aromatic compounds to form the chlorinated compounds.
基金supported by the National Natural Science Foundation of China (21622203, 21472147, 21272183)the Fund of Northwest University (334100036)
文摘Umpolung is a fundamental concept in organic chemistry, which provides an alternative strategy for the synthesis of target compounds which were not easily accessible by conventional methods. Herein, a mild and efficient PhI(OAc)_2-promoted umpolung acetoxylation reactions of enamides was developed for the synthesis of α-acetoxy ketones. The reaction tolerates a wide range of functional groups and affords α-acetoxy ketones in good to excellent yields. PhI(OAc)_2 serves as a source of acetoxy in the reaction.
基金C.Xu is grateful to Fuzhou University for the funding support(No.GXRC21051).
文摘The polysubstituted and spirocyclic cyclobutanes were efficiently constructed by the utilization of a novel skeletal contraction strategy which only took one-step synthesis from the readily accessible pyrrolidines.The mechanistic studies indicated that a key intermediate N-aminated pyrrolidine was formed initially and subsequent extrusion of a nitrogen via a radical pathway completed the transformation.This practical methodology was further highlighted by the concise,formal synthesis of the cytotoxic natural product piperarborenine B.
