Review
Chemistry, Multidisciplinary
Weichao Xue, Xiao Jia, Xuan Wang, Xianghua Tao, Zhigang Yin, Hegui Gong
Summary: The transformation of sterically hindered tertiary alkyl electrophiles under nickel-catalyzed conditions to forge C(sp(3))-C bonds and create all-carbon quaternary centers has received increasing attention in recent years. This process involves the activation of tertiary alkyl electrophiles through ionic or radical pathways, benefiting the formation of C-C bonds in coupling reactions and accelerating radical addition reactions.
CHEMICAL SOCIETY REVIEWS
(2021)
Article
Chemistry, Organic
Yang Ye, Guobin Ma, Ken Yao, Hegui Gong
Summary: A general, mild, and scalable method for hydrodeoxygenation of tertiary alkyl oxalates by Zn/silane under Ni-catalyzed conditions is described. The method is suitable for a variety of structural motifs derived from tertiary alcohols, including the synthesis of a key intermediate en route to estrone.
Article
Chemistry, Organic
Qing Wang, Ling Yue, Yanyang Bao, Yanan Wang, Danni Kang, Yan Gao, Zheliang Yuan
Summary: In this work, a photoredox-catalyzed gem-difluoroallylation was reported for the construction of all-carbon quaternary centers using oxalates as activating groups for tertiary alcohols. Efficient tertiary radical addition to alpha-trifluoromethyl alkenes enabled the formation of these challenging structures. The method showed good functional group tolerance for both alpha-trifluoromethyl alkenes and oxalates, and was successfully applied to the synthesis of monofluoralkenes.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Yuxin Gong, Zhaodong Zhu, Qun Qian, Weiqi Tong, Hegui Gong
Summary: This method describes the facile construction of sterically hindered tertiary alkyl ethers and thioethers via Zn(OTf)(2)-catalyzed coupling and Cu(OTf)(2)-catalyzed thiolation of unactivated tertiary alkyl bromides and oxalates, respectively. It represents one of the most effective conditions for forming unactivated tertiary C(sp(3))-heteroatom bonds through readily accessible Lewis acid catalysis, which surprisingly is less developed in the field.
Article
Chemistry, Multidisciplinary
Zhaobin Wang, Ze-Peng Yang, Gregory C. Fu
Summary: The development of efficient methods, particularly catalytic and enantioselective processes, for the construction of all-carbon quaternary stereocentres is an important and difficult challenge in organic synthesis. A nickel-based chiral catalyst has been shown to achieve enantioconvergent couplings of tertiary electrophiles with alkenylmetal nucleophiles, providing access to a variety of organic compounds with good yield and enantioselectivity. This approach offers a potentially versatile strategy for the synthesis of complex molecules, including natural product intermediates.
Article
Chemistry, Organic
Zhen Wang, Yi-Xin Wang, Xiao-Hui Yang
Summary: This work presents an efficient and atom-economic rhodium and thiophenol co-catalyzed hydroheteroarylation of styrenes with heteroarenes. Alkylated unprotected heteroarenes are obtained with low catalyst loading. This protocol provides a direct access to indoles bearing an all-carbon quaternary center at the C3-position.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Naoki Tsuchiya, Tetsuhiro Yamamoto, Hiroki Akagawa, Takashi Nishikata
Summary: In this study, we report a copper-catalyzed stereospecific fluorination reaction involving CsF and a-bromocarboxamides as tertiary alkyl sources. Unlike traditional stereospecific routes, this reaction proceeds with retention of stereochemistry. This stereospecific Cu-catalyzed reaction is an efficient method for synthesizing fluorinated molecules with highly congested stereogenic carbon centers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Farbod A. Moghadam, Elliot F. Hicks, Zachary P. Sercel, Alexander Q. Cusumano, Michael D. Bartberger, Brian M. Stoltz
Summary: An enantioselective iridium-catalyzed allylic alkylation of malonates with trisubstituted allylic electrophiles to form all-carbon quaternary stereocenters is reported. This reaction proceeds at ambient temperature and enables the preparation of a wide range of enantioenriched products in up to 93% yield and 97% ee. The quaternary products can be readily converted to several valuable building blocks such as vicinal quaternary products and beta-quaternary acids.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Mayuko Isomura, David A. Petrone, Erick M. Carreira
Summary: A robust catalytic system utilizing chiral Ir-phosphoramidite and La(OTf)(3) enables highly enantioselective alkylation reactions of racemic tertiary alpha-allenyl alcohols with tetrasubstituted silyl ketene acetals. The reaction displays broad functional group tolerance and allows efficient generation of beta-allenyl ester products with excellent enantioselectivity, which can be further upgraded in structural complexity via stereoselective metal-catalyzed functionalization reactions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Huan Xiang, Zhengkai Yu, Tian Xie, Xiang-Yang Ye, Yang Ye
Summary: A facile and efficient method for the synthesis of hindered 6-alkylated phenanthridine is presented using Zn-mediated reductive trapping of tertiary alkyl radicals with both electron-rich and electron-deficient aryl isocyanides, and nickel as a promoter. The reaction exhibits excellent functional group tolerance and broad substrate scope.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Arko Das, Harshit Joshi, Vinod K. Singh
Summary: An enantioselective approach for synthesizing fluorinated azaarenes with vicinal quaternary-tertiary stereocenters has been summarized, utilizing a chiral copper(I)-phosphine complex to bind with the azaarenes followed by Michael addition to unsaturated acyl imidazoles, resulting in highly enantioselective compounds with excellent yields. Further functionalization of the acyl imidazole part has also been demonstrated.
Article
Chemistry, Organic
Sebastian Ye, Martin G. Banwell
Summary: Through a reaction sequence involving Suzuki-Miyaura cross-coupling and Eschen-moser-Claisen rearrangement processes, the enantiomerically pure bromobenzene-derived metabolite 5 has been transformed into enone 20, followed by the formation of 4,4-disubstituted cyclohexa-2,5-dienone 21 and congener 22. A similar sequence can also convert the starting material 5 into compound ent-22.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Shuai Huang, Gao-Peng Zhang, Yang-Jie Jiang, Fei-Le Yu, Chang-Hua Ding, Xue-Long Hou
Summary: This article presents a facile and efficient method for constructing vicinal tertiary and quaternary chiral carbon centers in synthetic chemistry. By using Kundig-type chiral N-heterocyclic carbene as the ligand, the reaction between Pd-catalyzed umpolung asymmetric allylic alkylation of hydrazones and monosubstituted allyl reagents achieves high yields and high selectivities.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Clayton P. Donald, Amy Boylan, Truong N. Nguyen, Po-An Chen, Jeremy A. May
Summary: The (IPr)GaCl3/AgSbF6, AgSbF6, and GaCl3 catalysts were found to efficiently catalyze the substitution of the hydroxyl group of secondary and tertiary propargylic alcohols with organoboronic acids via C-C bond formation, and GaCl3 catalyst effectively synthesized all-carbon quaternary propargylic centers. These catalysts demonstrated the ability to perform substitutions at carbons bearing alkyl substituents, a capability that was lacking in other systems. The study showed that highly hindered carbon stereocenters, including quaternary centers bearing doubly ortho-substituted aryl rings, could be accessed efficiently using this method.
Article
Chemistry, Organic
Yue Ji, Xue Zhang, Ya Wu, Ze-Lin Dang, Wei-Wei Han, Si-Chang Wang, San-Bao Dong, Qun-Zheng Zhang
Summary: A facile and efficient synthesis method for tetrahydroisoquinolines with quaternary centers has been achieved through the sequential oxidation of N-bromosuccinimide and cyanation of tertiary amines. This compatible combination protocol allows for one-pot synthesis of α-cyano tetrahydroisoquinolines containing a quaternary center with a yield of up to 99%.
TETRAHEDRON LETTERS
(2022)
Article
Chemistry, Organic
Bing Xu, Yang Ye, Ying Lin, Renren Bai, Xiang-Yang Ye, Tian Xie
Summary: In this study, we present a simple method for the plain manufacture of sterically hindered tertiary alkyl thioethers via the Cu-catalyzed coupling of unactivated tertiary alkyl alcohols with thio-alcohols/phenols. This method represents one of the most effective unactivated tertiary C (sp(3))-S bond-forming methods via readily accessible Lewis acid catalysis under easy-to-operate reaction conditions. Moreover, it has high functional group compatibility and wide substrate adaptability.
TETRAHEDRON LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Yuxin Gong, Lei Su, Zhaodong Zhu, Yang Ye, Hegui Gong
Summary: In this study, a mild and easy-to-operate Ni-catalyzed arylation and alkylation reaction was reported using Zn and tBuOOtBu as the external reductant and oxidant. This reaction enables carbofunctionalization of C(sp(3))-H bonds and preparation of intermediates of bioactive compounds and drug derivatives.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Xingrui He, Hang Zhang, Yingqian Zhang, Yang Ye, Shuo Wang, Renren Bai, Tian Xie, Xiang-Yang Ye
Summary: Post-translational modifications (PTMs) of histone by histone demethylases (KDMs) are important for gene expression regulation and are implicated in the development of various human cancers and diseases. This review surveys the latest small-molecule inhibitors of KDMs, focusing on literature since 2018, including inhibitors of lysine-specific demethylases (LSD or KDM1) and JmjC family N-methyl lysine demethylases (JmjC KDMs, i.e. KDM2-7). The review also discusses drug design strategy, structure-activity relationships (SARs), analysis of co-crystal structures, and mechanisms of action (MOA).
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Haifeng Chen, Huifeng Yue, Chen Zhu, Magnus Rueping
Summary: This study describes a nickel-catalyzed three-component reductive carbonylation reaction for the synthesis of aryl-alkyl ketones. Ethyl chloroformate is used as a safe and readily available source of CO, providing an efficient and practical alternative. Experimental and mechanistic studies provide insight into the complexity and sequence of the reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Chen Zhu, Shao-Chi Lee, Haifeng Chen, Huifeng Yue, Magnus Rueping
Summary: This paper presents a reductive cross-coupling reaction between alpha-oxy halides generated from aldehydes and various C(sp(2))- and C(sp)-electrophiles, achieving the formation of protected alcohols and alpha-hydroxy ketones. The interchange of different catalytic strategies indicates underlying mechanistic similarities, with the generation of Ni-I intermediate proposed as a key point for ketyl radical formation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Haowen Deng, Jianshe Wang, Wei He, Yang Ye, Renren Bai, Xuelei Zhang, Xiang-Yang Ye, Tian Xie, Zi Hui
Summary: In this study, a simpler, greener and more efficient microwave-assisted protocol was developed to rapidly synthesize chiral oxazolines using aryl nitriles or cyano-containing compounds and chiral beta-amino alcohols as starting materials. The reaction can proceed smoothly in either concentrated solution or under solvent-free conditions with the presence of a recoverable heterogeneous catalyst. This method offers advantages of rapidness, convenience, environmental protection, high atom economy, and excellent yields, making it suitable for wider application in the community.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Haifeng Chen, Chen Zhu, Huifeng Yue, Magnus Rueping
Summary: In this study, a nickel-catalyzed, three-component reductive protocol for group 14 element hetero-difunctionalization of 1,3-enynes using electrochemistry is described. The method is mild, selective, and general, allowing for the silyl-, germanyl-, and stannyl-alkylation of enynes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Bing Xu, Huan Xiang, Yuqiong Tan, Ze Li, Shijun Li, Xiang-Yang Ye, Yang Ye
Summary: This paper describes an efficient strategy for promoting alkenyl thioetherifications through the Ni-catalyzed cross-coupling of inactivated or beta-aryl-substituted (E)-alkenyl halides with thio-alcohols/phenols. This strategy represents one of the most effective methods for forming alkenyl C(sp2)-S bonds using readily accessible nickel catalysis under easy-to-operate reaction conditions. The work also demonstrates the broad scope of this strategy, including the synthesis of protected amino acids, saccharides, and heterocycles, as well as its application in late-stage modifications of structurally complex natural products and pharmaceuticals.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Haifeng Chen, Chen Zhu, Huifeng Yue, Magnus Rueping
Summary: An efficient cobalt-catalyzed carbon-germanium bond formation method has been developed, providing access to a wide range of functionalized germane-containing compounds. This method shows a broad scope and good tolerance toward various functional groups, and is conducted under mild reaction conditions. Mechanistic studies shed light on the unexpected reaction pathway and sequential activation of different electrophiles.
Review
Chemistry, Multidisciplinary
Liang Zou, Yuan Gao, Qiaoman Zhang, Xiang-Yang Ye, Tian Xie, Li-Wei Wang, Yang Ye
Summary: The domino cyclization/coupling strategy is an effective method to produce cyclized and multi-functionalized compounds from olefins, attracting significant attention for its enantiocontrol potential. Recent studies have focused on achieving difunctionalization of substituted olefins through an asymmetric domino intramolecular cyclization/cascade reaction, which is useful for synthesizing complex natural products and drugs. This review provides a classification of reaction types and summarizes the recent advances in this field, serving as a knowledge resource and accelerating research progress.
CHEMISTRY-AN ASIAN JOURNAL
(2023)
Review
Chemistry, Multidisciplinary
Huimin Yang, Yang Ye
Summary: The construction of C-C and C-X bonds is crucial in organic synthesis and methodology. Recent studies on transition metal-catalyzed functionalization of alkenes have shown their increasing importance. Transition metals with a large number of electrons in the d-orbit exhibit a wider range of applicable reactions. Among them, nickel has become a popular choice due to its ability to form alkyl nickel intermediates that can couple with various nucleophiles or electrophiles. Nickel also offers the flexibility of multiple oxidation valence states, enabling diverse catalytic cycles.
TOPICS IN CURRENT CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Yingqian Zhang, Chenyuan Wu, Nana Zhang, Rui Fan, Yang Ye, Jun Xu
Summary: Pyrazole derivatives, a class of heterocyclic compounds, possess unique chemical structures and exhibit a broad spectrum of pharmacological activities. Recent studies have focused on synthesizing and evaluating pyrazole derivatives for their anticancer potential. Structure-activity relationship studies have shown that appropriate substitution on the pyrazole ring can enhance anticancer efficacy and selectivity. Furthermore, these derivatives have demonstrated multiple mechanisms of anticancer action, making them promising candidates for developing anticancer drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Organic
Ying Lin, Liang Zou, Renren Bai, Xiang-Yang Ye, Tian Xie, Yang Ye
Summary: We present an easy and efficient method for vinylation using Fe-catalyzed cross-electrophile coupling of readily available vinyl- and hydro-chlorosilanes with a range of substituted alkenyl bromides using manganese as the terminal reductant. This modular approach allows the formation of various vinyl orgaonosilanes, including electron-rich, electron-poor, and ortho-/meta-/para-substituted vinyl electrophiles, with excellent functional group tolerance and broad substrate scope. Furthermore, this method successfully modified substrates with structurally complex natural products and pharmaceutical motifs, demonstrating its potential in gram-scale reactions and derivatization.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Review
Chemistry, Organic
Yang Ye, Ying Lin, Nian-Dong Mao, Huimin Yang, Xiang-Yang Ye, Tian Xie
Summary: Alkenes are versatile building blocks in organic synthesis, and transition metal catalyzed difunctionalization reactions provide efficient access to substituted molecules. Nickel-based catalytic complexes have attracted attention due to their oxidative addition and slow beta-hydride elimination abilities. Various Ni-catalyzed cross-coupling methods have been developed, allowing for broad scopes and high tolerance to functional groups. However, challenges remain in expanding the types of carboboration reactions, diversifying electrophile types, and understanding the reaction mechanisms.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Yang Ye, Xiang Qi, Bing Xu, Ying Lin, Huan Xiang, Liang Zou, Xiang-Yang Ye, Tian Xie
Summary: In this study, a facile and efficient allylation method via nickel-catalyzed cross-electrophile coupling using zinc as the terminal reductant was developed. This modular approach demonstrated excellent functional group tolerance and broad substrate scope, leading to the synthesis of various 1,4-dienes including structurally complex natural products and pharmaceutical motifs. The coupling strategy also showed potential for enantiomeric control.
