The lithihum (a-carbalkoxyvinyl) (2-thienyl) mixed higher order cyanocuprate, de-rived from ethyl propargylic ester with (n-C13H27) (2-thienyl)CuCNLi2, reacted with cis-1-bromo-l-propylene under Pd (PPh3)4 catalysis t...The lithihum (a-carbalkoxyvinyl) (2-thienyl) mixed higher order cyanocuprate, de-rived from ethyl propargylic ester with (n-C13H27) (2-thienyl)CuCNLi2, reacted with cis-1-bromo-l-propylene under Pd (PPh3)4 catalysis to give a diene ester ethyl 1- (Z-propylidene)-1-E-hexadecenate. Then the target product (±)-litsenolide C2 was stereoselectively synthe-sized by employing cis-dihydroxylation of the diene ester using a NMO-OsO4 system as the oxidant and stereospecific lactonation by acidic catalyst. The ratio of E to Z carbon-carbon double bond is >98: 2, and the ratio of trans- and cis-disubstituted lactones is >95: 5.展开更多
This paper summarizes significant progress in quantifying organic substituent effects in the last 20 years. The main content is as follows： （1） The principle of electronegativity equalization has gained wide accept...This paper summarizes significant progress in quantifying organic substituent effects in the last 20 years. The main content is as follows： （1） The principle of electronegativity equalization has gained wide acceptance, and has been used to calculate the intramolecular charge distribution and inductive effect of groups. A valence electrons equalization method was proposed to compute the molecular electronegativity on the basis of geometric mean method, harmonic mean method, and weighted mean method. This new calculation method further extended the application of the principle of electronegativity equalization. （2） A scale method was established for experimentally determining the electrophilic and nucleophilic ability of reagents, in which benzhydryliumions and quinone methides were taken as the reference compounds, and the research field was extended to the gas phase conditions, organometallic reaction and radicals system. Moreover, the nucleophilicity parameters N and electro- philicity parameters E for a series of reagents were obtained. The definition and quantitative expression of electrophilicity in- dex co and nucleophilicity index co were proposed theoretically, and the correlation between the parameters from experimental determination and the indexes from theoretical calculation was also investigated. （3） The polarizability effect parameter was initially calculated by empirical method and further developed by quantum chemistry method. Recently, the polarizability ef- fect index of alkyl （PEI） and groups （PEIx） were proposed by statistical method, and got wide applications in explaining and estimating gas-phase acidity and basicity, ionization energy, enthalpy of formation, bond energy, reaction rate, water solubility and chromatographic retention for organic compounds. （4） The excited-state substituent constant Crcc obtained directly from the UV absorption energy data of substituted benzenes, is different from the polar constants in molecular ground state and the radical spin-delocalization effects constants in molecular radical state. The proposed constant Crcc correlated well with the UV absorption energy of many kinds of organic compounds, such as 1,4-disubstituted benzenes, substituted stilbenes, and di- substituted N-benzylidenebenzenamine. （5） The establishment of the steric shielding effect distinguished the three traditional steric effects. The stereoselectivity index Ci was proposed to quantify the stereoselectivity of the addition reaction of carbonyl with nucleophilic reagent. The shielding parameter Rs was defined to quantitatively express the specific surface of the reac- tion center screened by a group. Further, the Topological Steric Effect Index （TSEI） of a group was proposed on the basis of the relative specific volume of reaction center screened by the atoms of substituents. These parameters can be applied in esti- mating the intramolecular dihedral angles, stereoselectivity of reaction, enthalpies of formation of alkenes and alkylbenzene, acidity of substitutedimidazolium ionic liquid, and the reaction rate of alkane and hydroxyl radical. In addition, some sugges- tions and prospects for further studies on quantifying the organic substituent effects were presented in this paper.展开更多
Stereochemical control is an important issue in carbohydrate synthesis.Glycosyl donors with participating acyl protective groups on 2-O have been shown to give 1,2-trans glycosides reliably under the pre-activation ba...Stereochemical control is an important issue in carbohydrate synthesis.Glycosyl donors with participating acyl protective groups on 2-O have been shown to give 1,2-trans glycosides reliably under the pre-activation based reaction condition.In this work,the effects of additives and reaction solvents on stereoselectivity were examined using donors without participating protective groups on 2-O.While several triflate salt additives did not have major effects,the amount of AgOTf was found to significantly impact the reaction outcome.Excess AgOTf led to lower stereochemical control presumably due to its coordination with the glycosyl triflate intermediate and a more SN1 like reaction pathway.In contrast,the stereoselectivity could be directed by reaction solvents,with diethyl ether favoring the formation of glycosides and dichloromethane leading to β isomers.The trend of stereochemical dependence on reaction solvent was applicable to a variety of building blocks including the selective formation of β-mannosides.展开更多
Imidazo[1,2-a]pyridines are present in numerous biologically active compounds as the core structural motif.Herein,we report an asymmetric interrupted Barton-Zard reaction of electron-deficient imidazo[1,2-a]pyridines ...Imidazo[1,2-a]pyridines are present in numerous biologically active compounds as the core structural motif.Herein,we report an asymmetric interrupted Barton-Zard reaction of electron-deficient imidazo[1,2-a]pyridines withα-substituted isocyanoacetates.The reaction enables the dearomatization of 8-nitroimidazo[1,2-a]pyridines and hence offers straightforward access to an array of optically active highly functionalized imidazo[1,2-a]pyridine derivatives that possess three contiguous stereogenic centers in good yields(up to 98%)with high stereoselectivities(>19:1 dr,>99%ee).It is worth noting that the catalytic system consisting of a chiral squaramide and silver oxide displays remarkable reactivity and stereoselectivity,and a gram-scale reaction is compatible with the catalyst loading of 0.5 mol%.In addition,the synthetic potential of this method was showcased by versatile transformations of the product.展开更多
A facile and efficient method for the stereoselective synthesis of β-amino acid esters via SmI2-promoted imino-Reformatsky reaction is described.Asymmetric addition of tert-butyl bromoacetate to N-tert-butanesulfinyl...A facile and efficient method for the stereoselective synthesis of β-amino acid esters via SmI2-promoted imino-Reformatsky reaction is described.Asymmetric addition of tert-butyl bromoacetate to N-tert-butanesulfinyl aldimines afforded β-amino acid esters in moderate to high yields with excellent diastereoselectivities.The synthetic utilities of the tert-butyl β-amino acid esters were expanded by the preparation of β-lactams and 3-aminoindan-1-ones derivatives.展开更多
文摘The lithihum (a-carbalkoxyvinyl) (2-thienyl) mixed higher order cyanocuprate, de-rived from ethyl propargylic ester with (n-C13H27) (2-thienyl)CuCNLi2, reacted with cis-1-bromo-l-propylene under Pd (PPh3)4 catalysis to give a diene ester ethyl 1- (Z-propylidene)-1-E-hexadecenate. Then the target product (±)-litsenolide C2 was stereoselectively synthe-sized by employing cis-dihydroxylation of the diene ester using a NMO-OsO4 system as the oxidant and stereospecific lactonation by acidic catalyst. The ratio of E to Z carbon-carbon double bond is >98: 2, and the ratio of trans- and cis-disubstituted lactones is >95: 5.
基金financially supported by the National Natural Science Foundation of China (21272063, 21072053, 20772028, 20472019 and20172043)the Scientific Research Fund of Hunan Provincial Education Department (10K025)
文摘This paper summarizes significant progress in quantifying organic substituent effects in the last 20 years. The main content is as follows： （1） The principle of electronegativity equalization has gained wide acceptance, and has been used to calculate the intramolecular charge distribution and inductive effect of groups. A valence electrons equalization method was proposed to compute the molecular electronegativity on the basis of geometric mean method, harmonic mean method, and weighted mean method. This new calculation method further extended the application of the principle of electronegativity equalization. （2） A scale method was established for experimentally determining the electrophilic and nucleophilic ability of reagents, in which benzhydryliumions and quinone methides were taken as the reference compounds, and the research field was extended to the gas phase conditions, organometallic reaction and radicals system. Moreover, the nucleophilicity parameters N and electro- philicity parameters E for a series of reagents were obtained. The definition and quantitative expression of electrophilicity in- dex co and nucleophilicity index co were proposed theoretically, and the correlation between the parameters from experimental determination and the indexes from theoretical calculation was also investigated. （3） The polarizability effect parameter was initially calculated by empirical method and further developed by quantum chemistry method. Recently, the polarizability ef- fect index of alkyl （PEI） and groups （PEIx） were proposed by statistical method, and got wide applications in explaining and estimating gas-phase acidity and basicity, ionization energy, enthalpy of formation, bond energy, reaction rate, water solubility and chromatographic retention for organic compounds. （4） The excited-state substituent constant Crcc obtained directly from the UV absorption energy data of substituted benzenes, is different from the polar constants in molecular ground state and the radical spin-delocalization effects constants in molecular radical state. The proposed constant Crcc correlated well with the UV absorption energy of many kinds of organic compounds, such as 1,4-disubstituted benzenes, substituted stilbenes, and di- substituted N-benzylidenebenzenamine. （5） The establishment of the steric shielding effect distinguished the three traditional steric effects. The stereoselectivity index Ci was proposed to quantify the stereoselectivity of the addition reaction of carbonyl with nucleophilic reagent. The shielding parameter Rs was defined to quantitatively express the specific surface of the reac- tion center screened by a group. Further, the Topological Steric Effect Index （TSEI） of a group was proposed on the basis of the relative specific volume of reaction center screened by the atoms of substituents. These parameters can be applied in esti- mating the intramolecular dihedral angles, stereoselectivity of reaction, enthalpies of formation of alkenes and alkylbenzene, acidity of substitutedimidazolium ionic liquid, and the reaction rate of alkane and hydroxyl radical. In addition, some sugges- tions and prospects for further studies on quantifying the organic substituent effects were presented in this paper.
基金the National Institutes of Health (R01-GM-72667) for financial support of this work
文摘Stereochemical control is an important issue in carbohydrate synthesis.Glycosyl donors with participating acyl protective groups on 2-O have been shown to give 1,2-trans glycosides reliably under the pre-activation based reaction condition.In this work,the effects of additives and reaction solvents on stereoselectivity were examined using donors without participating protective groups on 2-O.While several triflate salt additives did not have major effects,the amount of AgOTf was found to significantly impact the reaction outcome.Excess AgOTf led to lower stereochemical control presumably due to its coordination with the glycosyl triflate intermediate and a more SN1 like reaction pathway.In contrast,the stereoselectivity could be directed by reaction solvents,with diethyl ether favoring the formation of glycosides and dichloromethane leading to β isomers.The trend of stereochemical dependence on reaction solvent was applicable to a variety of building blocks including the selective formation of β-mannosides.
基金supported by the National Key R&D Program of China(2021YFA1500100)the National Natural Science Foundation of China(21821002,22031012,and 22171282)the Science and Technology Commission of Shanghai Municipality(19590750400 and 21520780100)。
文摘Imidazo[1,2-a]pyridines are present in numerous biologically active compounds as the core structural motif.Herein,we report an asymmetric interrupted Barton-Zard reaction of electron-deficient imidazo[1,2-a]pyridines withα-substituted isocyanoacetates.The reaction enables the dearomatization of 8-nitroimidazo[1,2-a]pyridines and hence offers straightforward access to an array of optically active highly functionalized imidazo[1,2-a]pyridine derivatives that possess three contiguous stereogenic centers in good yields(up to 98%)with high stereoselectivities(>19:1 dr,>99%ee).It is worth noting that the catalytic system consisting of a chiral squaramide and silver oxide displays remarkable reactivity and stereoselectivity,and a gram-scale reaction is compatible with the catalyst loading of 0.5 mol%.In addition,the synthetic potential of this method was showcased by versatile transformations of the product.
基金Financial support from the National Natural Science Foundation of China (20721003)the Chinese Academy of Sciences, the State Key Laboratory of Drug Research, SIMM and National Science & Technology Major Project (2009ZX09301-001 & 2008ZX09401-004) is acknowledged
文摘A facile and efficient method for the stereoselective synthesis of β-amino acid esters via SmI2-promoted imino-Reformatsky reaction is described.Asymmetric addition of tert-butyl bromoacetate to N-tert-butanesulfinyl aldimines afforded β-amino acid esters in moderate to high yields with excellent diastereoselectivities.The synthetic utilities of the tert-butyl β-amino acid esters were expanded by the preparation of β-lactams and 3-aminoindan-1-ones derivatives.
