Article
Chemistry, Physical
Fangfang Guo, Jiean Chen, Yong Huang
Summary: Recently, chiral N-heterocyclic carbenes (NHCs) have been established as powerful catalysts for enantioselective bond-forming processes via noncovalent interactions. A bifunctional NHC with an embedded hydrogen-bonding motif has been reported in this study, showing remarkable tolerance of various Michael acceptors in an asymmetric aza-conjugate addition reaction, with catalytic efficiency far exceeding that of the benchmark tertiary amine-thiourea scaffold.
Review
Chemistry, Multidisciplinary
Guangcai Xu, Gerrit J. Poelarends
Summary: The application of biocatalysis in challenging synthesis has greatly benefited from the development of new enzymes. By incorporating catalysis modes from synthetic chemistry, novel biocatalysts have been created, and the design of iminium catalysis plays a fundamental role in this process. It has been shown that repurposing existing enzymes or constructing artificial enzymes can promote valuable abiological transformations, demonstrating the power of combining chemomimetic biocatalyst design and directed evolution in generating new-to-nature enzymes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Applied
Andrea Guerrero-Corella, Miguel A. Valle-Amores, Alberto Fraile, Jose Aleman
Summary: An asymmetric organocatalytic aza-Michael addition reaction of ketimines to nitroolefins is described, utilizing 2-hydroxybenzophenone imine to improve the enantioselective addition of N-centered nucleophiles to nitroalkenes. The versatility of the process is demonstrated under both batch and flow conditions, resulting in the synthesis of a wide variety of nitroamine derivatives with excellent yields and enantioselectivities. Additionally, this methodology was successfully applied to the formal synthesis of VNI, a drug-like scaffold for the treatment of Chagas disease.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Applied
Irma Garcia-Monzon, Jorge Borges-Gonzalez, Tomas Martin
Summary: The heterogenization of homogeneous catalysts onto a solid support is a crucial step towards sustainable chemistry. In this study, we developed a series of polymer-supported tetrahydropyran-based hybrid dipeptides as active catalysts for the enantioselective Michael addition of aldehydes to beta-nitrostyrenes. The optimal anchor position and orientation between the catalyst and solid support, as well as the linker length, were carefully designed to enhance the catalytic efficiency. These supported catalysts exhibited high yields and enantiomeric excesses, and detailed deactivation studies provided important insights for prolonging their useful life.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Zhao-Fei Zhang, Zhong-Hua Gao, Chun-Lin Zhang, Song Ye
Summary: The intramolecular aza-Michael addition of alkyl amines to α,β-unsaturated carboxylic acids catalyzed by N-heterocyclic carbenes has been successfully achieved, allowing for the synthesis of pyrrolidine and piperidine derivatives. The use of chiral NHC catalysts demonstrated promising enantioselectivities up to 55% ee. Further chemical transformations of the products provided carboxylic acids, alcohols, and unprotected amines.
Review
Chemistry, Applied
Yong-Xing Song, Da-Ming Du
Summary: The aza-Michael addition cascade reaction is an important synthetic method for constructing functionalized C-N bonds, widely used in the synthesis of chiral drugs, intermediates, and natural products. This review highlights recent developments in asymmetric synthesis, including various types of aza-Michael addition triggered cascade reactions, reaction mechanisms, and derivatization experiments.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Jade A. Bing, Jeffrey N. Johnston
Summary: The synthesis of 7-membered carbocyclic fi-fluoro-amines is achieved by combining the enantioselective aza-Henry reaction of aliphatic N-Boc imines and ring-closing metathesis. Reductive denitration is used to obtain both diastereomers of the fi-fluoro amine carbocycle, each with high enantiomeric excess.
Article
Chemistry, Applied
Fabian Scharinger, Matthias Weil, Michael Schnuerch, Katharina Bica-Schroeder
Summary: We introduce a simple method for the synthesis of chiral diazabicycloalkanes in a single reaction step. This method is applicable to a wide range of enals and has high functional group tolerance.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Jing Cao, Antonia Seitz, Jose A. Forni, Anastasios Polyzos, David W. Lupton
Summary: This article reports on a reaction design that avoids the facile oxidation of phosphine organocatalyst and combines traditional nucleophilic phosphine organocatalysis with photoredox catalysis to enable Giese coupling with ynoates. The approach exhibits good generality, and its mechanism is supported by cyclic voltametric, Stern-Volmer quenching, and interception studies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Applied
Laura A. Bryant, Kenneth Shankland, Hannah E. Straker, Callum D. Johnston, Nicholas R. Lees, Alexander J. A. Cobb
Summary: The article describes a rare organocatalytic intramolecular cyclization of resorcinols with a high enantioselectivity using a specific organocatalyst. The obtained bicyclic resorcinols show excellent utility in the synthesis of cannabinoid-like compounds, and exhibit anticonvulsant activity.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Multidisciplinary
En Li, Jiean Chen, Yong Huang
Summary: The Michael reaction is an important method for preparing functional molecules with a β-stereogenic center. However, the enantioselective seleno-Michael addition is still poorly explored. In this study, a highly enantioselective Michael addition reaction of alkyl selenols to enones was reported, introducing a Se atom asymmetrically to an electron-deficient double bond. A chiral bifunctional N-heterocyclic carbene (NHC)/thiourea catalyst was developed and showed remarkable selectivity in delivering chiral β-seleno ketones.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Xiao-Yan Dong, Da-Ming Du
Summary: This paper investigated the organocatalytic asymmetric 1,4-Michael addition reaction of azadienes and alpha-thiocyanoindanones, successfully synthesizing a series of chiral thiocyano compounds. By describing a possible reaction mechanism, it broadens the scope of application of azadiene substrates.
Article
Chemistry, Applied
Jen-Yu Kuan, I-Ting Chen, Hsuan Lin, Jeng-Liang Han
Summary: We have developed a substrate-dependent, regio- and stereocontrolled diversity-oriented organocatalytic vinylogous Michael addition/cyclization cascade of 2-alkylidene indane-1,3-diones with enals, using secondary amines as the catalyst. This method allows for the selective synthesis of spiroindane-1,3-diones, tetrahydrofluoren-9-one derivatives, and benzofused oxabicyclo[3.3.1]nonanes. Plausible catalytic pathways have been proposed, and DFT calculations have clarified the mechanisms involved.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Abhisek Midya, Laxman Devidas Khalse, Prasanta Ghorai
Summary: In this study, an amine-catalyzed reductive aldol-condensation followed by an intramolecular reductive Michael-addition cascade was demonstrated, using Hantzsch ester as a hydride source to a keto-bis-enone, leading to the synthesis of enantio- and diastereoselective benzannulated diquinanes with three consecutive stereocenters, including an all-carbon quaternary formyl stereocenter. Interestingly, changing the tether from an aliphatic to an aromatic moiety resulted in a change in reactivity, where an asymmetric aldol reaction, followed by an iminium/enamine isomerization and diastereoselective Michael addition reaction, resulted in the formation of a bis-benzannulated diquinane with vicinal congested quaternary chiral centers.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Abhisek Midya, Laxman Devidas Khalse, Prasanta Ghorai
Summary: An unprecedented enantioselective organocatalytic spirocyclization strategy was developed by in situ generation of aminoisobenzofulvenes and utilizing iminium-enamine catalysis for a reductive Michael/aldol-condensation/Michael addition cascade. This strategy showed remarkable success in the synthesis of all carbon quaternary spirocycles and demonstrated post-methodological manipulation of the products.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Yu-Hua Deng, Wen-Dao Chu, Xiang-Zhi Zhang, Xu Yan, Ke-Yin Yu, Liang-Liang Yang, Hanmin Huang, Chun-An Fan
JOURNAL OF ORGANIC CHEMISTRY
(2017)
Article
Chemistry, Organic
Ji-Yuan Du, Xian-Tao An, Xian-He Zhao, Xiao-Yan Ma, Ye-Xing Cao, Chun-An Fan
Article
Chemistry, Organic
Zhi-Gang Ma, Jie-Lu Wei, Jun-Bing Lin, Guan-Jun Wang, Jia Zhou, Kai Chen, Chun-An Fan, Shu-Yu Zhang
Article
Chemistry, Organic
Ting Pan, Pan Shi, Bo Chen, Da-Gang Zhou, Ya-Li Zeng, Wen-Dao Chu, Long He, Quan-Zhong Liu, Chun-An Fan
Article
Chemistry, Multidisciplinary
Xian-Tao An, Ji-Yuan Du, Zhi-Long Jia, Qing Zhang, Ke-Yin Yu, Yi-Zhou Zhang, Xian-He Zhao, Ran Fang, Chun-An Fan
CHEMISTRY-A EUROPEAN JOURNAL
(2020)
Article
Chemistry, Organic
Zhi-Long Jia, Xian-Tao An, Yu-Hua Deng, Hui-Bin Wang, Kang-Ji Gan, Jing Zhang, Xian-He Zhao, Chun-An Fan
Article
Chemistry, Organic
Yu-Hua Deng, Wen-Dao Chu, Yun-Han Shang, Ke-Yin Yu, Zhi-Long Jia, Chun-An Fan
Article
Chemistry, Organic
Zhi-Long Jia, Xian-Tao An, Yu-Hua Deng, Lin-Han Pang, Chun-Fang Liu, Le-Le Meng, Jia-Kun Xue, Xian-He Zhao, Chun-An Fan
Summary: An unprecedented asymmetric catalytic (4 + 2) annulation reaction has been developed for the synthesis of chiral cyclohexadienone-fused cyclohexyl spirooxindoles using aryl-substituted gamma-methylidene-delta-valerolactones (GMDVs) and isatin-derived para-quinone methides (p-QMs) catalyzed by palladium(0) and (S,S,S)-(-)-Xyl-SKP. This reaction can efficiently and selectively forge three highly congested contiguous tetrasubstituted carbon atoms, including two vicinal quaternary stereogenic centers.
Article
Chemistry, Multidisciplinary
Ye-Xing Cao, Patamawadee Silalai, Chun-Fang Liu, Ke-Yin Yu, Xu Bao, Xian-He Zhao, Rungnapha Saeeng, Chun-An Fan
Summary: This study presents a novel hypervalent-iodine(III)-mediated tandem reaction for the synthesis of structurally interesting and synthetically useful aziridines. The resulting densely functionalized aziridines offer a platform for accessing architecturally diverse aza-heterocycles through selective ring-opening transformations initiated by the reaction.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Organic
Ke-Yin Yu, Yu-Hua Deng, Xiao-Min Ge, Xian-Tao An, Peng-Fei Shu, Ye-Xing Cao, Xian-He Zhao, Chun-An Fan
Summary: A new tandem annulation reaction between p-quinone methides and ynamides has been described, resulting in the synthesis of functionalized aminoindene compounds. The reaction involves a unique structural rearrangement of p-QMs, with cleavage of the C5-C6 bond and late-stage formation of the C4-C6 bond, leading to the development of a methodology for constructing functionalized aminoindenes.
Article
Chemistry, Organic
Xu Yan, Chun-Fang Liu, Xian-Tao An, Xiao-Min Ge, Qing Zhang, Lin-Han Pang, Xu Bao, Chun-An Fan
Summary: A novel strategy based on Cu-catalyzed (4+1) cascade annulation of terminal alkynes with 2-(tosylmethyl)anilines has been developed for the expeditious synthesis of 2,3-disubstituted indoles, involving in situ generations of aza-o-quinone methides and alkynyl-copper(I) species. This annulation provides an effective method for the assembly of synthetically and structurally interesting 2,3-disubstituted indoles.
Article
Chemistry, Organic
Hu Qu, Xin-Shen Liang, Wen-Juan Wang, Xian-He Zhao, Yu-Hua Deng, Xian-Tao An, Wen-Dao Chu, Xiang-Zhi Zhang, Chun-An Fan
Summary: Triacylamines with Cs symmetry have been studied in asymmetric organocatalysis, leading to the development of a novel catalytic enantioselective reaction for prochiral triacylamines. This method provides an effective approach for synthesizing chiral imide-esters with a 1,5-dicarbonyl moiety, and has been successfully applied in the asymmetric synthesis of two GABA analogue drugs.
Article
Chemistry, Multidisciplinary
Xian -He Zhao, Le -Le Meng, Xiao-Tao Liu, Peng-Fei Shu, Cheng Yuan, Xian -Tao An, Tian-Xi Jia, Qi-Qiong Yang, Xiang Zhen, Chun-An Fan
Summary: A unified strategy for asymmetric divergent syntheses of nine C8-ethano-bridged diterpenoids has been developed based on late-stage transformations of common synthons. This strategy allows for the efficient synthesis of these compounds through the regioselective and diastereoselective cyclization reactions of specific functional groups. The successful synthesis of these compounds demonstrates the versatility and reactivity of densely functionalized polycyclic substrates.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Xian-Tao An, Xiao-Min Ge, Xin-Yu Liu, Yu-Han Yang, Xian-He Zhao, Xiao-Yan Ma, Chao Peng, Yi-Jun Fan, Yong Qin, Chun-An Fan
Summary: A new strategy for the asymmetric assembly of the ring D in (-)-cephalotaxine has been developed. This strategy involves a novel Rh-catalyzed annulation reaction for enantioselective construction of the cyclopentane ring D with a spirocyclic aza-quaternary stereocenter. Using this strategy, a concise enantioselective total synthesis of (-)-cephalotaxine has been achieved in nine steps from readily available starting materials. Additionally, the synthesis of related compounds (-)-cephalotine B, (-)-fortuneicyclidin B, and (-)-fortuneicyclidin A has also been accomplished.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Ke-Yin Yu, Xiao-Min Ge, Yi-Jun Fan, Xiao-Tao Liu, Xue Yang, Yu-Han Yang, Xian-He Zhao, Xian-Tao An, Chun-An Fan
Summary: The unique reactivity of indolyl-substituted p-QMs as a new type of two-carbon synthon in a novel iron(iii)-catalyzed tandem annulation has been explored for the first time. The (2+2) annulation/retro-4 pi electrocyclization/imino-Nazarov cyclization cascade reaction is characterized by an unusual structural reconstruction of indolyl-substituted p-QMs, leading to the rapid assembly of synthetically important functionalized cyclopenta[b]indoles.
CHEMICAL COMMUNICATIONS
(2022)