Article
Chemistry, Multidisciplinary
Titouan Desrues, Jeremy Merad, Daniela Andrei, Jean-Marc Pons, Jean-Luc Parrain, Maurice Medebielle, Adrien Quintard, Cyril Bressy
Summary: This study reported an enantioselective organocatalyzed acylation of alpha,alpha-difluorohydrins using a commercially available chiral isothiourea, greatly improving the enantioselectivity of the kinetic resolution process through electrostatic fluorine-cation interactions. The method allows for the synthesis of various fluorinated alcohols with exquisite enantiocontrol, such as 4,4-difluoro-1,3-diols, as well as demonstrated compatibility between aromatic and fluorinated groups in providing enantioenriched adducts.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Xueyang Liu, Jean-Marc Pons, Valerie Monnier, Laurence Charles, Adrien Quintard, Cyril Bressy
Summary: This paper describes an efficient enantioselective kinetic resolution method for the separation of secondary alcohols with a quaternary stereocenter. It utilizes a commercially available chiral isothiourea organocatalyst and achieves high levels of stereoselectivity in a wide range.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Applied
Yongkai Pan, Qianwen Jiang, Subramani Rajkumar, Chaofan Zhu, Jinglei Xie, Shaoze Yu, Yunrong Chen, Yu-Peng He, Xiaoyu Yang
Summary: A series of cyclohexyl-fused SPINOL-derived phosphoric acids have been developed for the kinetic resolution of 2-N-acylamido tertiary allylic alcohols, providing access to chiral oxazolines with high enantioselectivities. Gram-scale reactions with 1 mol% catalyst loading and transformations of the chiral products demonstrate the value of these methods.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Review
Chemistry, Organic
Bo Ding, Qilin Xue, Shihu Jia, Hong-Gang Cheng, Qianghui Zhou
Summary: This review provides an overview of recent advances in catalytic nonenzymatic kinetic resolution (KR) of tertiary alcohols, including organocatalysis and metal catalysis.
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Multidisciplinary
Min Gao, Yanshu Luo, Qianlan Xu, Yukun Zhao, Xiangnan Gong, Yuanzhi Xia, Lin Hu
Summary: The research achieved a unified catalytic asymmetric (N+1) (N=4, 5) annulation reaction of oxindoles with bifunctional peroxides using a chiral phase-transfer catalyst (PTC). This method provides a distinct way to access valuable chiral spirooxindole-tetrahydrofurans and -tetrahydropyrans with good yields and high enantioselectivities under mild conditions. The DFT calculations were performed to rationalize the high enantioselectivity observed in the reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Jihoon Moon, Takusho Kin, Karin Mizuno, Shuji Akai, Kyohei Kanomata
Summary: This study presents a chemoenzymatic dynamic kinetic resolution (DKR) of racemic sec-alcohols using immobilized lipase and aqueous sulfuric acid as catalysts for kinetic resolution and racemization, respectively. The use of nanoparticle-stabilized phase separation in a Pickering emulsion allowed the use of these incompatible catalysts in a single vessel. The racemization reaction in the aqueous sulfuric acid solution effectively suppressed side reactions, resulting in high yields and optical purities.
Article
Chemistry, Multidisciplinary
Yi Gong, Cai Wang, Feng Zhou, Kui Liao, Xi-Yu Wang, Ying Sun, Yan-Xue Zhang, Zhi Tu, Xin Wang, Jian Zhou
Summary: This study presents the first highly selective kinetic resolution of racemic alpha-chiral azides through Cu-catalyzed azide-alkyne cycloaddition (CuAAC). Newly developed pyridine-bisoxazoline (PYBOX) ligands bearing a C4 sulfonyl group enabled effective kinetic resolution and asymmetric CuAAC of racemic azides derived from privileged scaffolds such as indanone, cyclopentenone, and oxindole, leading to alpha-tertiary 1,2,3-triazoles with high to excellent ee values. DFT calculations and control experiments revealed that the C4 sulfonyl group decreased the Lewis basicity of the ligand and increased the electrophilicity of the copper center for better recognition of azides, while also functioning as a shielding group to enhance the efficacy of the chiral pocket of the catalyst.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Sushovan Paladhi, Si Joon Park, In-Soo Hwang, Jin Hyun Park, Han Yong Bae, Amol P. Jadhav, Choong Eui Song
Summary: In this study, a biomimetic catalytic retro-aldol reaction using a chiral oligoEG cation-binding catalyst as a mimic of type-II aldolase was described. The investigation of various aldol substrates showed that our biomimetic retro-aldol protocol allows for rapid access to highly enantiomerically enriched aldols with a selectivity factor (s) of up to 70. Additionally, the feasibility of the synthetic strategy for accessing diverse and valuable axially chiral aldehydes was demonstrated.
Article
Chemistry, Multidisciplinary
Daniel Moser, Kalipada Jana, Christof Sparr
Summary: In this study, the feasibility of atroposelective P-III/P-V=O redox organocatalysis by the Staudinger-aza-Wittig reaction is described. The formation of isoquinoline heterocycles allows for the synthesis of a wide range of valuable atropisomers with high enantioselectivities. The reaction is catalyzed by a chiral phosphine catalyst, with stereocontrol achieved through a silane reductant and Bronsted acid co-catalysis. The products can be easily transformed into N-oxides, naphthol, and triaryl phosphine variants, providing access to diverse aromatic heterocycles with precise control over their configuration.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Chemistry, Organic
Helene Pellissier
Summary: Organocatalytic dynamic kinetic resolution (DKR) has emerged as a promising field in the past two decades, allowing efficient separation of chiral compounds. This review aims to provide an update on organocatalytic DKRs since 2016.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Dan Hu, Si Bei Poh, Feipeng Liu, Zhifeng Tu, Xia Wang, Shenci Lu, Yu Zhao
Summary: The effect of counter-anions on enantio-control in oxidative NHC catalysis is systematically investigated in this study. The results demonstrate that the identity of counter-anions has a significant impact on the enantioselectivity of the catalytic system, and highly efficient kinetic resolution can be achieved by selecting appropriate counter-anions.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Ken Okuno, Yasuaki Furuya, Seiji Shirakawa
Summary: The kinetic resolution of racemic compounds is a reliable method to prepare chiral molecules in highly optically enriched forms. However, the kinetic resolution of racemic carboxylic acids has not been well developed. Esterification and lactonization promoted by chiral organocatalysts have been found to be effective methods for the kinetic resolution of chiral carboxylic acids.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Avene C. Colgan, Rupert S. J. Proctor, David C. Gibson, Padon Chuentragool, Antti S. K. Lahdenpera, Kristaps Ermanis, Robert J. Phipps
Summary: This study reports a significant advancement in the catalytic enantioselective Minisci reaction, allowing the use of α-hydroxy radical coupling partners to obtain valuable enantioenriched secondary alcohol products. The approach is highly regioselective as well as highly enantioselective.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Yunrong Chen, Chaofan Zhu, Zheng Guo, Wei Liu, Xiaoyu Yang
Summary: The first kinetic resolution of hydroquinoline derivatives with alpha,alpha-disubstitution has been achieved through asymmetric remote aminations with azodicarboxylates enabled by chiral phosphoric acid catalysis. Mechanistic studies suggest a monomeric catalyst pathway proceeding through rate- and enantio-determining electrophilic attack promoted by a network of attractive non-covalent interactions between the substrate and catalyst. Facile subsequent removal and transformations of the newly introduced hydrazine moiety enable these protocols to serve as powerful tools for asymmetric synthesis of N-heterocycles with alpha,alpha-disubstitution.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Tibor Penaska, Viktoria Modrocka, Klara Stankovianska, Maria Meciarova, Erik Rakovsky, Radovan Sebesta
Summary: This study achieves enantioselective and diastereoselective synthesis of densely substituted chiral pyran derivatives by using amino-thiourea or quinine organocatalyst under ball-milling conditions. Liquid-assisted grinding proves to be a highly efficient means of obtaining pyrans in high yield, with high enantiomeric purities and short reaction times.
Article
Chemistry, Multidisciplinary
Yunrong Chen, Chaofan Zhu, Zheng Guo, Wei Liu, Xiaoyu Yang
Summary: The first kinetic resolution of hydroquinoline derivatives with alpha,alpha-disubstitution has been achieved through asymmetric remote aminations with azodicarboxylates enabled by chiral phosphoric acid catalysis. Mechanistic studies suggest a monomeric catalyst pathway proceeding through rate- and enantio-determining electrophilic attack promoted by a network of attractive non-covalent interactions between the substrate and catalyst. Facile subsequent removal and transformations of the newly introduced hydrazine moiety enable these protocols to serve as powerful tools for asymmetric synthesis of N-heterocycles with alpha,alpha-disubstitution.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Organic
Wei Liu, Xiaoyu Yang
Summary: Chiral phosphoric acids have been recognized as one of the most powerful chiral organocatalysts and have been extensively applied in kinetic resolution, dynamic kinetic resolution and desymmetrization reactions, leading to significant developments in these areas since 2016.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Chaofan Zhu, Wei Liu, Fei Zhao, Yunrong Chen, Houchao Tao, Yu-Peng He, Xiaoyu Yang
Summary: A novel kinetic resolution of 2,2-disubstituted dihydroquinolines was achieved through regioselective asymmetric halogenations enabled by chiral phosphoric acid catalysis. The reactions showed good tolerance for a series of 2,2-disubstituted dihydroquinolines, generating both the recovered dihydroquinolines and C-6-brominated products with high enantioselectivities. Additionally, this kinetic resolution protocol is also applicable for 2,2-disubstituted tetrahydroquinolines and asymmetric iodonation reactions.
Article
Chemistry, Multidisciplinary
Mengyao Tang, Huanchao Gu, Shunlong He, Subramani Rajkumar, Xiaoyu Yang
Summary: An efficient protocol for kinetic resolution of tertiary alcohols has been developed via unprecedented asymmetric enamide-imine tautomerism process enabled by chiral phosphoric acid catalysis. This method is particularly effective for a series of 1,1-dialkyl substituted allyl alcohols, producing chiral tertiary alcohols that are difficult to access through other asymmetric methods. Facile and versatile transformations of the chiral products demonstrate the value of this kinetic resolution method.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Qianwen Jiang, Tianren Qin, Xiaoyu Yang
Summary: A novel protocol for asymmetric synthesis of hydroquinazolines with C4-tetrasubstituted stereocenters has been developed, involving kinetic resolution of 2-amido alpha-tertiary benzylamines using chiral phosphoric acid catalyzed intramolecular dehydrative cyclizations. This method provides access to both alpha-tertiary benzylamines and hydroquinazolines with high enantioselectivities and broad scope. An intriguing restricted rotation of the C-N bond was observed for hydroquinazoline products bearing C4-tetrasubstituted stereocenters.
Article
Chemistry, Multidisciplinary
Donglei Wang, Ying-Bo Shao, Yunrong Chen, Xiao-Song Xue, Xiaoyu Yang
Summary: An efficient method for the asymmetric synthesis of planar-chiral macrocycles (paracyclophanes) has been developed using chiral phosphoric acid catalysis for enantioselective electrophilic aromatic aminations with azodicarboxylates. This method allows for the synthesis of a wide range of chiral macrocycles with varying ring sizes and functional groups, achieving high yields and enantioselectivities. The mechanism and origins of the stereoselectivities of these reactions were investigated through experimental studies and computational calculations. Preliminary utilization of the planar-chiral macrocycle as a chiral organocatalyst demonstrated the potential applications of these novel chiral skeletons.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Jinglei Xie, Zheng Guo, Wei Liu, Dekun Zhang, Yu-Peng He, Xiaoyu Yang
Summary: An efficient kinetic resolution (KR) protocol for 1,2-diamines has been developed using chiral phosphoric acid catalysis. This method exhibits high enantioselectivity and is compatible with a wide range of substituted 1,2-diamines. Notably, it represents the first successful KR of 1,2-diamines bearing alpha-tertiary amine moieties.
CHINESE JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Organic
Wei Liu, Donglei Wang, Dekun Zhang, Xiaoyu Yang
Summary: Optically active amines are crucial in bioactive natural products, pharmaceuticals, chiral catalysts, and ligands. The development of nonenzymatic asymmetric catalytic approaches for the kinetic resolution and desymmetrization of amines in the past two decades has been systematically summarized.
Review
Chemistry, Multidisciplinary
Wei Liu, Tianren Qin, Wansen Xie, Xiaoyu Yang
Summary: Helicenes and helicene-like molecules with unique helical chirality have found wide applications in various research fields. However, the catalytic enantioselective synthesis of helicenes has been relatively underexplored. In the past two decades, significant progress has been made in this field, including methods enabled by both transition metal catalysis and organocatalysis.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Physical
Dekun Zhang, Ying-Bo Shao, Wansen Xie, Yunrong Chen, Wei Liu, Hanyang Bao, Faqian He, Xiao-Song Xue, Xiaoyu Yang
Summary: In this paper, a remote enantioselective desymmetrization protocol for asymmetric aromatic aminations of 9,10-dihydroacridines is disclosed. A new spirocyclic chiral phosphoric acid (CPA) catalyst is used to achieve this synthesis, leading to a wide range of chiral dihydroacridines with excellent enantioselectivities. This method is also applicable in the construction of stereogenic silicon center and kinetic resolution of unsymmetrical dihydroacridine derivatives. Density functional theory calculations elucidate the origin of the reactions' excellent regio- and enantioselectivity.
Article
Chemistry, Multidisciplinary
Hanyang Bao, Yunrong Chen, Xiaoyu Yang
Summary: In this study, a highly efficient catalytic asymmetric synthesis of diaryl ether atropisomers was reported via an organocatalyzed enantioselective desymmetrization protocol. The chiral phosphoric acid-catalyzed asymmetric electrophilic aromatic aminations of symmetrical substrates provided a series of diaryl ether atropisomers with excellent yields and enantioselectivities. The utilization of the 1,2-benzenediamine moiety in the products allowed for the facile construction of heterocycles, leading to a wide range of structurally diverse and novel azaarene-containing diaryl ether atropisomers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Wei Liu, Tianren Qin, Wansen Xie, Jinmiao Zhou, Zidan Ye, Xiaoyu Yang
Summary: We have developed an efficient modular asymmetric synthesis of azahelicenes from readily available polycyclic aromatic amines, aldehydes, and (di)enamides, employing a central-to-helical chirality conversion strategy. A series of aza[5]- and aza[4]helicenes bearing various substituents were easily obtained with good yields and high enantioselectivities. The diverse derivatizations and the preliminary application of the azahelicene derivative as a chiral organocatalyst demonstrated the potential of this method, and the photophysical and chiroptical properties of these azahelicenes were well studied, showing potential applications in novel organic optoelectronic materials.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Zidan Ye, Wei Liu, Huanchao Gu, Xiaoyu Yang
Summary: Highly efficient and stereoselective dearomatization of substituted phenols was achieved through chiral phosphoric acid-catalyzed electrophilic para-amination. This method readily provides chiral 2,5-cyclohexadienones bearing 4-aza-quaternary stereocenters with excellent yields and enantioselectivities (≤99% yield and >99% ee). The reaction can be easily scaled up to gram scale and the chiral products can be easily derivatized into α-tertiary amines and α-tertiary heterocycles derivatives, demonstrating the potential of this method.
Article
Multidisciplinary Sciences
Shaoze Yu, Hanyang Bao, Dekun Zhang, Xiaoyu Yang
Summary: This work reports an efficient and versatile kinetic resolution protocol for various substituted amido[2.2]paracyclophanes using chiral phosphoric acid (CPA)-catalyzed asymmetric amination reaction. The reaction mechanism for the electrophilic aromatic C-H amination is also elucidated, involving sequential triazane formation and N[1,5]-rearrangement.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Shaoze Yu, Guosong Shen, Faqian He, Xiaoyu Yang
Summary: A novel method for enantioselective macrocyclization has been developed, which involves chiral phosphoric acid-catalyzed intramolecular addition of the hydroxy group with the allenamide moiety. Planar-chiral macrocycles of various ring sizes and functional groups were generated with good to high enantioselectivities.
CHEMICAL COMMUNICATIONS
(2022)
