It is a challenge to separate the enantiomers of native chiral amines prone to deleterious silanol interactions. Aset of 39 underivatized chiral primary amines was screened for enantiomeric separation. Seven recentlyi...It is a challenge to separate the enantiomers of native chiral amines prone to deleterious silanol interactions. Aset of 39 underivatized chiral primary amines was screened for enantiomeric separation. Seven recentlyintroduced commercial chiral columns were tested. They included six polysaccharide based chiral stationaryphases (CSP) with bonded derivatives, ChiralPak? IA, IB, IC, ID, IE and IF columns and a cyclofructanderivatized CSP, Larihc? CF6-P column. Both the normal phase (NP) mode with heptane/alcohol mobile phasesand the polar organic (PO) mode with acetonitrile/alcohol were evaluated. It was found that the cyclofructanbased CSP demonstrated the highest success rate in separating primary amines in the PO mode with only onechiral amine not resolved. It is shown that, when screening the columns, there is no standard optimal condition;an excellent mobile phase composition for one column may be poorly suited to another one. Althoughbutylamine was a good mobile phase additive for the polysaccharide columns in both PO and NP modes, it wasdetrimental to the enantio-recognition capability of the cyclofructan column. Triethylamine was the appropriatesilanol screening agent for this latter column.展开更多
A highly efficient catalytic system composed of a simple and commercially available chiral primary diamine（1R,2R）-cyclohexane-1,2-diamine（6） and trifluoroacetic acid（TFA） was employed for asymmetric Aldol reacti...A highly efficient catalytic system composed of a simple and commercially available chiral primary diamine（1R,2R）-cyclohexane-1,2-diamine（6） and trifluoroacetic acid（TFA） was employed for asymmetric Aldol reaction in i-PrOH at room temperature.A loading of 10%（molar fraction） catalyst 6 with TFA as a cocatalyst could catalyze the Aldol reactions of various ketones or aldehydes with a series of aromatic aldehydes,furnishing Aldol products in moderate to high yields（up to 99%） with enantioselectivities of up to 99% and diastereoselectivities of up to 99：1.展开更多
Direct alkylation with skipped enynes or cyclopropropylacetylenes represents an ideal process for the installation of pentadienyl group in terms of atom- and step-economy.The development of catalytic asymmetric versio...Direct alkylation with skipped enynes or cyclopropropylacetylenes represents an ideal process for the installation of pentadienyl group in terms of atom- and step-economy.The development of catalytic asymmetric versions has been frequently pursued and most of the successes have been achieved with enolizable aldehydes.We herein describe a synergistic chiral primary amine/Pd catalysis for asymmetric α-pentadienylation of β-ketocarbonyls and aldehydes with skipped enynes or cyclopropropylacetylenes.The reaction features the construction of acyclic all-carbon quaternary centers with high enantioselectivity,and good functional group tolerance and scalability.展开更多
We report herein the first example of asymmetric hydroazidation of α-substituted vinyl ketones by using chiral primary amines as the catalysts.A simple chiral primary-tertiary diamine catalyst derived from lphenylala...We report herein the first example of asymmetric hydroazidation of α-substituted vinyl ketones by using chiral primary amines as the catalysts.A simple chiral primary-tertiary diamine catalyst derived from lphenylalanine was found to readily promote this aza-Michael addition reaction with enamine protonation as the key stereogenic step,thus enabling the effective synthesis of α-chiral β-azido ketones with good yields and moderate enantioselectivities.展开更多
Esters are abundant in natural and synthetic products and their conversion into primary alcohols holds great importance in fine chemical synthesis.However,achieving asymmetric hydrogenation(AH)of racemic esters with r...Esters are abundant in natural and synthetic products and their conversion into primary alcohols holds great importance in fine chemical synthesis.However,achieving asymmetric hydrogenation(AH)of racemic esters with remote stereocenters via kinetic resolution(KR)remains a formidable challenge due to the difficulties associated with discerning spatially distant stereocenters.To address this issue,we have designed a hydroxy-assisted strategy that introduces a hydroxy group into racemicβ-aryl esters to facilitate hydrogenation and enhance chiral discrimination through a lactone form.By employing chiral Ir-SpiroPAP catalysts,we achieved exceptional AH of racemic 4-substituted chroman-2-ones,lactone form of ortho-hydroxylatedβ-aryl esters,via KR,resulting in impressive selectivity factor(s)values of up to 600.This approach exhibited significant efficacy for racemic chroman-2-ones containingβ-aryl,alkenyl,alkynyl,and alkyl groups,enabling the synthesis of chiralγ-aryl primary alcohols and the recovery of chiralβ-aryl esters or chroman-2-ones,typically difficult to access using existing methods.The scalability and broad synthetic applications of this method were exemplified by successfully synthesizing chiral drugs(R)-fesoterodine and enrasentan,alongside various chiral intermediates essential for producing chiral drugs and natural products.These promising results highlight the potential of this approach as a powerful tool for synthesizing valuable chiral compounds.展开更多
Herein,we report tunable asymmetric addition and telomerization of butadiene by synergistic chiral primary amine/achiral palladium catalysis.A selection of different achiral phosphine ligand in concert with the chiral...Herein,we report tunable asymmetric addition and telomerization of butadiene by synergistic chiral primary amine/achiral palladium catalysis.A selection of different achiral phosphine ligand in concert with the chiral primary amine-trifluoromethanesulfonic acid(TfOH)conjugates enables both chemo-and enantioselective control of the coupling with butadiene.Bidentate[(oxydi-2,1-phenylene)-bis-(diphenylphosphine)](DPEPhos)ligand led to 1,4-addition adduct whereas monodentate(p-Tol)3P ligand gave the telomerization product.A range ofα-branchedβ-ketoesters and aldehydes could be applied to afford allylation or telomerization products bearing allcarbon quaternary centers at high efficiency and good chemo-,regio-,and stereoselectivities.展开更多
基金supported by the Robert A.Welch Foundation(Y-0026)the University of Texas at Arlington.A.Berthod thanks the French National Center for Scientific Research ISA UMR5280 for continuous support
文摘It is a challenge to separate the enantiomers of native chiral amines prone to deleterious silanol interactions. Aset of 39 underivatized chiral primary amines was screened for enantiomeric separation. Seven recentlyintroduced commercial chiral columns were tested. They included six polysaccharide based chiral stationaryphases (CSP) with bonded derivatives, ChiralPak? IA, IB, IC, ID, IE and IF columns and a cyclofructanderivatized CSP, Larihc? CF6-P column. Both the normal phase (NP) mode with heptane/alcohol mobile phasesand the polar organic (PO) mode with acetonitrile/alcohol were evaluated. It was found that the cyclofructanbased CSP demonstrated the highest success rate in separating primary amines in the PO mode with only onechiral amine not resolved. It is shown that, when screening the columns, there is no standard optimal condition;an excellent mobile phase composition for one column may be poorly suited to another one. Althoughbutylamine was a good mobile phase additive for the polysaccharide columns in both PO and NP modes, it wasdetrimental to the enantio-recognition capability of the cyclofructan column. Triethylamine was the appropriatesilanol screening agent for this latter column.
基金Supported by the National Basic Research Program of China(No.2010CB833300)the Research Fund for the Doctoral Program of Higher Education,China(No.20090031110019)
文摘A highly efficient catalytic system composed of a simple and commercially available chiral primary diamine（1R,2R）-cyclohexane-1,2-diamine（6） and trifluoroacetic acid（TFA） was employed for asymmetric Aldol reaction in i-PrOH at room temperature.A loading of 10%（molar fraction） catalyst 6 with TFA as a cocatalyst could catalyze the Aldol reactions of various ketones or aldehydes with a series of aromatic aldehydes,furnishing Aldol products in moderate to high yields（up to 99%） with enantioselectivities of up to 99% and diastereoselectivities of up to 99：1.
基金the Natural Science Foundation of China(21861132003 and 22031006)Tsinghua University Initiative Scientific Research Program for financial support.
文摘Direct alkylation with skipped enynes or cyclopropropylacetylenes represents an ideal process for the installation of pentadienyl group in terms of atom- and step-economy.The development of catalytic asymmetric versions has been frequently pursued and most of the successes have been achieved with enolizable aldehydes.We herein describe a synergistic chiral primary amine/Pd catalysis for asymmetric α-pentadienylation of β-ketocarbonyls and aldehydes with skipped enynes or cyclopropropylacetylenes.The reaction features the construction of acyclic all-carbon quaternary centers with high enantioselectivity,and good functional group tolerance and scalability.
基金National Natural Science Foundation of China(NSFC Nos.21390400,21521002 and 21502198)the Ministry of Science and Technology,Chinese Academy of Sciences(No.QYZDJSSW-SLH023)for generous financial supportsupported by National Program for Support of Top-notch Young Professionals,CAS Youth Innovation Promotion Association and CAS onehundred talented program(D)
文摘We report herein the first example of asymmetric hydroazidation of α-substituted vinyl ketones by using chiral primary amines as the catalysts.A simple chiral primary-tertiary diamine catalyst derived from lphenylalanine was found to readily promote this aza-Michael addition reaction with enamine protonation as the key stereogenic step,thus enabling the effective synthesis of α-chiral β-azido ketones with good yields and moderate enantioselectivities.
基金supported by the National Key R&D Program of China(grant no.2021YFA1500200)the National Natural Science Foundation of China(grant nos.92056105,92256303,22221002,and 22188101)the Fundamental Research Funds for the Central Universities,China,and the Haihe Laboratory of Sustainable Chemical Transformations,China.
文摘Esters are abundant in natural and synthetic products and their conversion into primary alcohols holds great importance in fine chemical synthesis.However,achieving asymmetric hydrogenation(AH)of racemic esters with remote stereocenters via kinetic resolution(KR)remains a formidable challenge due to the difficulties associated with discerning spatially distant stereocenters.To address this issue,we have designed a hydroxy-assisted strategy that introduces a hydroxy group into racemicβ-aryl esters to facilitate hydrogenation and enhance chiral discrimination through a lactone form.By employing chiral Ir-SpiroPAP catalysts,we achieved exceptional AH of racemic 4-substituted chroman-2-ones,lactone form of ortho-hydroxylatedβ-aryl esters,via KR,resulting in impressive selectivity factor(s)values of up to 600.This approach exhibited significant efficacy for racemic chroman-2-ones containingβ-aryl,alkenyl,alkynyl,and alkyl groups,enabling the synthesis of chiralγ-aryl primary alcohols and the recovery of chiralβ-aryl esters or chroman-2-ones,typically difficult to access using existing methods.The scalability and broad synthetic applications of this method were exemplified by successfully synthesizing chiral drugs(R)-fesoterodine and enrasentan,alongside various chiral intermediates essential for producing chiral drugs and natural products.These promising results highlight the potential of this approach as a powerful tool for synthesizing valuable chiral compounds.
基金the Natural Science Foundation of China(nos.21672217,21861132003,and 22031006)Tsinghua University Initiative Scientific Research Program for financial support.
文摘Herein,we report tunable asymmetric addition and telomerization of butadiene by synergistic chiral primary amine/achiral palladium catalysis.A selection of different achiral phosphine ligand in concert with the chiral primary amine-trifluoromethanesulfonic acid(TfOH)conjugates enables both chemo-and enantioselective control of the coupling with butadiene.Bidentate[(oxydi-2,1-phenylene)-bis-(diphenylphosphine)](DPEPhos)ligand led to 1,4-addition adduct whereas monodentate(p-Tol)3P ligand gave the telomerization product.A range ofα-branchedβ-ketoesters and aldehydes could be applied to afford allylation or telomerization products bearing allcarbon quaternary centers at high efficiency and good chemo-,regio-,and stereoselectivities.
