Enones are widely explored in synthetic chemistry as fundamental building blocks for a wide range of reactions and exhibit intriguing biological activities that are pivotal for drug discovery.The development of synthe...Enones are widely explored in synthetic chemistry as fundamental building blocks for a wide range of reactions and exhibit intriguing biological activities that are pivotal for drug discovery.The development of synthetic strategies for highly efficient preparation of enones thereby receives intense attention,in particular through the transition metal-catalyzed coupling reactions.Here,we describe a carbene-catalyzed cross dehydrogenative coupling(CDC)reaction that enables effective assembly of simple aldehydes and alkenes to afford a diverse set of enone derivatives.Mechanistically,the in situ generated aryl radical is pivotal to“activate”the alkene by forming an allyl radical through intermolecular hydrogen atom transfer(HAT)pathway and thus forging the carbon-carbon bond formation with aldehyde as the acyl synthon.Notably,our method represents the first example on the enone synthesis through coupling of“non-functionalized”aldehydes and alkenes as coupling partners,and offers a distinct organocatalytic pathway to the transition metal-catalyzed coupling transformations.展开更多
A series of novel chiral diphosphite ligands have been synthesized from（1R,2R）-trans-1,2-cyclohexanediol,（1S,2S）-trans-1,2-cyclohexanediol, racemic trans-1,2-cyclohexanediol and chlorophosphoric acid diary ester, ...A series of novel chiral diphosphite ligands have been synthesized from（1R,2R）-trans-1,2-cyclohexanediol,（1S,2S）-trans-1,2-cyclohexanediol, racemic trans-1,2-cyclohexanediol and chlorophosphoric acid diary ester, and were successfully employed in the Cu-catalyzed asymmetric 1,4-conjugate addition of diethylzinc to cyclohexenone with up to 99% ee. It was found that ligand 1,2-bis[（R）-1,10-binaphthyl-2,2＇-diyl]phosphitecyclohexanediol 6a derived from racemic diol skeleton can show similar catalytic performance compared with ligand（1R,2R）-bis[（R）-1,1＇-binaphthyl-2,2＇-diyl]phosphitecyclohexanediol 6a＇ derived from enantiopure starting material. A significant dependence of stereoselectivity on the type of enone and the ring size of the cyclic enone was observed. Moreover, the configuration of the products was mainly determined by the configuration of the binaphthyl moieties of diphosphite ligands in the 1,4-addition of cyclic enones.展开更多
Ni(0)-catalyzed regio-and diastereodivergent[4+2]annulation of biphenylenes withα,βunsaturated ketones is described.This solvent-controlled diastereodivergent reaction integrates C-C bond cleavage of biphenylene and...Ni(0)-catalyzed regio-and diastereodivergent[4+2]annulation of biphenylenes withα,βunsaturated ketones is described.This solvent-controlled diastereodivergent reaction integrates C-C bond cleavage of biphenylene and C=C double bond insertion selectivity,offering a mild approach to all possible diastereoisomers of 9,10-dihydrophenanthrene derivatives from the same starting materials.展开更多
A convergent approach to 1,5-hydroxy ketones,the general precursors for constructing the C ring of bryostatins,has been developed via a Zn/Cu-promoted conjugate addition of a-hydroxy iodides with enones.The reaction l...A convergent approach to 1,5-hydroxy ketones,the general precursors for constructing the C ring of bryostatins,has been developed via a Zn/Cu-promoted conjugate addition of a-hydroxy iodides with enones.The reaction leads to direct formation of the C21-C22 bond and tolerates diverse functionalities at the C17-,C18-and C24-positions.The approach also enables a more concise synthesis of the known C ring intermediate(10 longest linear steps and 14 total steps),in contrast to its previous synthesis(17 longest linear steps and 22 total steps) in our total synthesis of bryostatin 8.展开更多
Deconjugation of cyclopent-2-enone aldols were attempted under various conditions, and the desired deconjugated product was achieved via dianion approach. Various results obtained in this study are explained by struct...Deconjugation of cyclopent-2-enone aldols were attempted under various conditions, and the desired deconjugated product was achieved via dianion approach. Various results obtained in this study are explained by structure and transition state analysis.展开更多
The present paper narrates the addition of 5-trimethylsilylcyclohex-3-enone to Grig-nard reagent to give 1-substituted 5-trimethylsilylcyclohex-3-enol in a good yield. The stereochemistry of the addition reaction and ...The present paper narrates the addition of 5-trimethylsilylcyclohex-3-enone to Grig-nard reagent to give 1-substituted 5-trimethylsilylcyclohex-3-enol in a good yield. The stereochemistry of the addition reaction and their products are discussed.展开更多
In this study,we present an innovative and efficient approach to amine conjugation that offers many advantages over existing methods.Our method employs an easily preparedβ-alkoxy enone as the core reagent,achieving u...In this study,we present an innovative and efficient approach to amine conjugation that offers many advantages over existing methods.Our method employs an easily preparedβ-alkoxy enone as the core reagent,achieving unparalleled specificity to primary amines.It operates effectively under neutral pH conditions and at room temperature.This eliminates the need for metal catalysts or additives,thereby simplifying the process and reducing potential contaminants.A key attribute of our method is its remarkable cleanliness,with ethanol as the sole by-product,ensuring minimal environmental and biological impact.The conjugation products exhibit exceptional stability,even in the presence of diverse biomolecules,making this method highly suitable for intricate biological systems.Our approach demonstrates a broad substrate scope,effectively conjugating a range of compounds from lysine derivatives to complex protein and drug conjugates as well as amino-sugar conjugates.Its ability to selectively target different amine types while remaining unreactive toward anilines and secondary amines such as proline underscores its potential for advancing drug development and biologic synthesis.This method marks a significant breakthrough,offering promising avenues for exploration in biochemical and pharmaceutical research.展开更多
The asymmetric conjugate additions of aryl Grignard reagents to trisubstituted enones by chiral P,N ligand L6 with low catalyst loading(0.25–1.0 mol%)are disclosed.Chiral 2-ester chromanone and its analogs bearing a ...The asymmetric conjugate additions of aryl Grignard reagents to trisubstituted enones by chiral P,N ligand L6 with low catalyst loading(0.25–1.0 mol%)are disclosed.Chiral 2-ester chromanone and its analogs bearing a quaternary stereogenic centers at C2 position were produced in high to excellent yields,enantioselectivities and high turnover number.The notable features of this reaction include its broad substrate scope,complete 1,4-addition regioselectivities,applicability to both batch and flow for large scale synthesis.This report develops an efficient strategy to apply aryl Grignard reagents in asymmetric 1,4-conjugation reactions and provides a direct method to incorporate quaternary chiral centers toward the synthesis of biologically relevant chromanone derivatives.展开更多
Chiral sulfonamides derived from(d)-10-camphorsulfonyl chloride and chiral amines were prepared and used in the copper-catalyzed conjugate addition of organometallic reagents to enones.The chiral sulfonamides/CuCN cat...Chiral sulfonamides derived from(d)-10-camphorsulfonyl chloride and chiral amines were prepared and used in the copper-catalyzed conjugate addition of organometallic reagents to enones.The chiral sulfonamides/CuCN catalysts provided high catalytic activity and moderate enantioselectivity in the conjugate addition of diethylzinc to 2-cyclohexenone and 2-cyclohepteneone,but low enantioselectivity to the 2-cyclopentenone and acyclic enones.展开更多
Several cross-conjugate enone compounds with different electron withdrawing substituents have been synthesized. The spectroscopy and photophysical behavior of these compounds in different conditions were studied. Resu...Several cross-conjugate enone compounds with different electron withdrawing substituents have been synthesized. The spectroscopy and photophysical behavior of these compounds in different conditions were studied. Results show that TICT formation which depends strongly on the solvent polarity and electron withdrawing ability of substituents was observed for compounds with different electron withdrawing groups.For compound (Ⅳ) which possesses strong electron withdrawing ability, the TICT formation can be ob served in weak polar solvent, such as in toluene. But, for compounds (Ⅱ) and (Ⅲ), it can be observed in THF and ethyl ether, respectively. It can also be observed that the fluorescence quanum yields of these compounds are varied with the solvent polarity, and a maximum appears in this variation. Results obtaind have been discussed preliminary.展开更多
基金funding supports from the National Natural Science Foundation of China(Nos.21732002,22061007,22071036,and 22207022)Frontiers Science Center for Asymmetric Synthesis and Medicinal Molecules,National Natural Science Fund for Excellent Young Scientists Fund Program(Overseas),the starting grant of Guizhou University[No.(2022)47)]+10 种基金Department of Education,Guizhou Province[Qianjiaohe KY No.(2020)004]The 10 Talent Plan(Shicengci)of Guizhou Province(No.[2016]5649)Science and Technology Department of Guizhou Province(Nos.[Qiankehe-jichu-ZK[2022]zhongdian024],[2018]2802,[2019]1020,QKHJC-ZK[2022]-455)Department of Education of Guizhou Province(No.QJJ(2022)205)Program of Introducing Talents of Discipline to Universities of China(111 Program,No.D20023)at Guizhou UniversitySingapore National Research Foundation under its NRF Investigatorship(No.NRF-NRFI2016–06)Competitive Research Program(No.NRF-CRP22–2019–0002)Ministry of Education,Singapore,under its MOE Ac RF Tier 1 Award(Nos.RG7/20,RG70/21)MOE AcRF Tier 2(No.MOE2019-T2–2–117)MOE AcRF Tier 3 Award(No.MOE2018-T3–1–003)a Chair Professorship Grant,and Nanyang Technological University。
文摘Enones are widely explored in synthetic chemistry as fundamental building blocks for a wide range of reactions and exhibit intriguing biological activities that are pivotal for drug discovery.The development of synthetic strategies for highly efficient preparation of enones thereby receives intense attention,in particular through the transition metal-catalyzed coupling reactions.Here,we describe a carbene-catalyzed cross dehydrogenative coupling(CDC)reaction that enables effective assembly of simple aldehydes and alkenes to afford a diverse set of enone derivatives.Mechanistically,the in situ generated aryl radical is pivotal to“activate”the alkene by forming an allyl radical through intermolecular hydrogen atom transfer(HAT)pathway and thus forging the carbon-carbon bond formation with aldehyde as the acyl synthon.Notably,our method represents the first example on the enone synthesis through coupling of“non-functionalized”aldehydes and alkenes as coupling partners,and offers a distinct organocatalytic pathway to the transition metal-catalyzed coupling transformations.
基金the National Natural Science Foundation of China (Nos. 20773147, 21073211, and 21174155)
文摘A series of novel chiral diphosphite ligands have been synthesized from（1R,2R）-trans-1,2-cyclohexanediol,（1S,2S）-trans-1,2-cyclohexanediol, racemic trans-1,2-cyclohexanediol and chlorophosphoric acid diary ester, and were successfully employed in the Cu-catalyzed asymmetric 1,4-conjugate addition of diethylzinc to cyclohexenone with up to 99% ee. It was found that ligand 1,2-bis[（R）-1,10-binaphthyl-2,2＇-diyl]phosphitecyclohexanediol 6a derived from racemic diol skeleton can show similar catalytic performance compared with ligand（1R,2R）-bis[（R）-1,1＇-binaphthyl-2,2＇-diyl]phosphitecyclohexanediol 6a＇ derived from enantiopure starting material. A significant dependence of stereoselectivity on the type of enone and the ring size of the cyclic enone was observed. Moreover, the configuration of the products was mainly determined by the configuration of the binaphthyl moieties of diphosphite ligands in the 1,4-addition of cyclic enones.
基金supported by the National Natural Science Foundation of China (Nos. 21801067, U1804283, 21801066)the Central Plains Scholars and Scientists Studio Fund (No. 2018002)+2 种基金the Project funded by the Natural Science Foundation of Henan (Nos. 202300410225, 212300410181, 222102310562 and 201901023)China Postdoctoral Science Foundation (Nos. 2020T130176 and 2020M682306)financial support from Henan Key Laboratory of Organic Functional Molecules and Drug Innovation
文摘Ni(0)-catalyzed regio-and diastereodivergent[4+2]annulation of biphenylenes withα,βunsaturated ketones is described.This solvent-controlled diastereodivergent reaction integrates C-C bond cleavage of biphenylene and C=C double bond insertion selectivity,offering a mild approach to all possible diastereoisomers of 9,10-dihydrophenanthrene derivatives from the same starting materials.
基金the financial support from the National Natural Science Foundation of China(No.21921002)the NationalScience and Technology Major Project of the Ministry of Science and Technology of the People’s Republic of China(No.2018ZX09711001-005-004)the Fundamental Research Funds for the Central Universities(No.2012017yjsy210)。
文摘A convergent approach to 1,5-hydroxy ketones,the general precursors for constructing the C ring of bryostatins,has been developed via a Zn/Cu-promoted conjugate addition of a-hydroxy iodides with enones.The reaction leads to direct formation of the C21-C22 bond and tolerates diverse functionalities at the C17-,C18-and C24-positions.The approach also enables a more concise synthesis of the known C ring intermediate(10 longest linear steps and 14 total steps),in contrast to its previous synthesis(17 longest linear steps and 22 total steps) in our total synthesis of bryostatin 8.
文摘Deconjugation of cyclopent-2-enone aldols were attempted under various conditions, and the desired deconjugated product was achieved via dianion approach. Various results obtained in this study are explained by structure and transition state analysis.
基金Supported by the National Natural Science Foundation of China Youth Foundation of Tianjin
文摘The present paper narrates the addition of 5-trimethylsilylcyclohex-3-enone to Grig-nard reagent to give 1-substituted 5-trimethylsilylcyclohex-3-enol in a good yield. The stereochemistry of the addition reaction and their products are discussed.
基金support from a Distinguished University Professor grant(Nanyang Technological University)the Agency for Science,Technology,and Research(A*STAR)under its MTC Individual Research grant(M21K2c0114)and RIE2025 MTC Programmatic Fund(M22K9b0049)(to T.-P.L.).
文摘In this study,we present an innovative and efficient approach to amine conjugation that offers many advantages over existing methods.Our method employs an easily preparedβ-alkoxy enone as the core reagent,achieving unparalleled specificity to primary amines.It operates effectively under neutral pH conditions and at room temperature.This eliminates the need for metal catalysts or additives,thereby simplifying the process and reducing potential contaminants.A key attribute of our method is its remarkable cleanliness,with ethanol as the sole by-product,ensuring minimal environmental and biological impact.The conjugation products exhibit exceptional stability,even in the presence of diverse biomolecules,making this method highly suitable for intricate biological systems.Our approach demonstrates a broad substrate scope,effectively conjugating a range of compounds from lysine derivatives to complex protein and drug conjugates as well as amino-sugar conjugates.Its ability to selectively target different amine types while remaining unreactive toward anilines and secondary amines such as proline underscores its potential for advancing drug development and biologic synthesis.This method marks a significant breakthrough,offering promising avenues for exploration in biochemical and pharmaceutical research.
基金the financial support from the Sichuan Science and Technology Program(No.2022NSFSC0619)。
文摘The asymmetric conjugate additions of aryl Grignard reagents to trisubstituted enones by chiral P,N ligand L6 with low catalyst loading(0.25–1.0 mol%)are disclosed.Chiral 2-ester chromanone and its analogs bearing a quaternary stereogenic centers at C2 position were produced in high to excellent yields,enantioselectivities and high turnover number.The notable features of this reaction include its broad substrate scope,complete 1,4-addition regioselectivities,applicability to both batch and flow for large scale synthesis.This report develops an efficient strategy to apply aryl Grignard reagents in asymmetric 1,4-conjugation reactions and provides a direct method to incorporate quaternary chiral centers toward the synthesis of biologically relevant chromanone derivatives.
文摘Chiral sulfonamides derived from(d)-10-camphorsulfonyl chloride and chiral amines were prepared and used in the copper-catalyzed conjugate addition of organometallic reagents to enones.The chiral sulfonamides/CuCN catalysts provided high catalytic activity and moderate enantioselectivity in the conjugate addition of diethylzinc to 2-cyclohexenone and 2-cyclohepteneone,but low enantioselectivity to the 2-cyclopentenone and acyclic enones.
文摘Several cross-conjugate enone compounds with different electron withdrawing substituents have been synthesized. The spectroscopy and photophysical behavior of these compounds in different conditions were studied. Results show that TICT formation which depends strongly on the solvent polarity and electron withdrawing ability of substituents was observed for compounds with different electron withdrawing groups.For compound (Ⅳ) which possesses strong electron withdrawing ability, the TICT formation can be ob served in weak polar solvent, such as in toluene. But, for compounds (Ⅱ) and (Ⅲ), it can be observed in THF and ethyl ether, respectively. It can also be observed that the fluorescence quanum yields of these compounds are varied with the solvent polarity, and a maximum appears in this variation. Results obtaind have been discussed preliminary.
