Article
Chemistry, Multidisciplinary
Isaac Choi, Zhigao Shen, Emanuel Ronge, Volker Karius, Christian Jooss, Lutz Ackermann
Summary: A recyclable hybrid manganese catalyst has been developed for site-selective azine C-H activation with weak amide assistance. The catalyst enables C3-H arylation and C3-H alkylation reactions, and has been characterized using detailed transmission electron microscopy analysis.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Physical
Shrikant M. Khake, Ken Yamazaki, Yusuke Ano, Naoto Chatani
Summary: This study reports a branch-selective C-H alkenylation method using an iridium catalyst with alkenes, suitable for aniline derivatives containing a pyrimidine-directing group, offering a broad substrate scope and tolerating various functional groups. The origin of branch selectivity was investigated using density functional theory calculations.
Article
Chemistry, Organic
Zhenbang Chang, Saisai Zhang, Yinpeng Wang, Heng-Ying Xiong, Guangwu Zhang
Summary: This study demonstrates the coupling between heterocyclic N-oxides and CF3-ynones via formal C-H and C-C bond cleavage under catalyst-free and mild conditions. The reaction shows a broad substrate scope and potential application.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Physical
Binyang Jiang, Jia-Ming Liu, Shi-Liang Shi
Summary: Achieving site-selective C2-alkylation of pyridine using unactivated alkene as an alkylating reagent is a long-standing challenge. In this study, a bifunctional NHC-Ni-Al-pyridine complex under Ni-Al bimetallic catalysis and directing bifunctional N-heterocyclic carbene (NHC) as ligand was used to achieve high site selectivity and efficiency in the C2-alkylation of pyridine.
Article
Chemistry, Physical
Binyang Jiang, Jia-Ming Liu, Shi-Liang Shi
Summary: We report a method for achieving site-selective C2-alkylation of pyridine using unactivated alkenes as alkylating reagents under Ni-Al bimetallic catalysis and directing bifunctional N-heterocyclic carbene (NHC) as a ligand. The method allows for the efficient synthesis of a wide range of C2-alkylated pyridines with various functionalities, and can be extended to other azines such as pyrazines and pyrimidines. Mechanistic studies reveal that a bifunctional NHC-Ni-Al-pyridine complex is responsible for high site selectivity control, and reductive elimination may be the rate-determining step.
Article
Chemistry, Multidisciplinary
Sachin Balaso Mohite, Manoj V. Mane, Milan Bera, Rajshekhar Karpoormath
Summary: A controlled method for regiodivergent C-H olefination of Imidazo[1,2a] pyridine carboxamide and unactivated alkenes has been developed using Pd/MPAA catalyst. This method can generate branched or linear olefinated products depending on the electronic nature of the alkenes, and can also be applied for C-H deuteriation of heteroarenes.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Physical
Ge Yin, Yue Li, Rong-Hua Wang, Jiang-Fei Li, Xue-Tao Xu, Yu-Xin Luan, Mengchun Ye
Summary: Conventional C-H alkenylation of 2-pyridone with electron-deficient C-H bonds typically occurs at the C6 or C4 position using low-valent transition-metal catalysis. However, a Ni-Al bimetallic catalyst with a bifunctional ligand resulted in a reversed selectivity, providing high yields of C3-alkenylated 2-pyridones.
Article
Chemistry, Organic
Neha Taneja, Pragya Sharma, Naveen Yadav, Dulal Musib, Chinmoy Kumar Hazra
Summary: Here, we report a metal-free, nondirected, site-selective, and one-pot approach for the meta-arylation of arylamines. This method, catalyzed by a Bronsted acid, enables direct C-C bond formation and offers a wide range of substrate scope and scalability. It overrides the traditional site-selectivity to produce meta-substituted anilines. The protocol is also applicable for meta-allylation of anilines and can be extended to late-stage functionalization and synthesis of highly functionalized anilines and medicinally privileged arylated diamines. Control experiments and density functional theory studies support the proposed mechanism and selectivity.
Article
Chemistry, Applied
Shanhong Wan, Zhenli Luo, Xin Xu, Haiyang Yu, Jiajie Li, Yixiao Pan, Xin Zhang, Lijin Xu, Rui Cao
Summary: A Mn(I)-catalyzed chelation-assisted direct C6-H alkenylation of 2-pyridones with both terminal and internal alkynes has been developed, leading to high yields of the products. Mechanistic studies indicate the involvement of a five-membered organomanganese as the key intermediate.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Physical
Yoshimi Kato, Tatsuhiko Yoshino, Shigeki Matsunaga
Summary: C-H functionalization reactions catalyzed by iron, the most abundant transition metallic element in the Earth's crust, are one of the ideal synthetic methods. However, there are a limited number of strategies for iron-catalyzed directed C-H activation reactions when compared to reactions catalyzed by other first-row transition metals. Here, we report the iron/photosensitizer-catalyzed C-H alkenylation of amide derivatives via a a-CAM promoted by the in situ generation of an iron metallacycle. Mechanistic experiments suggest that the C-H bond cleavage would proceed via the a-CAM from a metallacycle generated in situ rather than via the oxidative addition to a low-valent iron species.
Article
Chemistry, Organic
Yuanshuang Xu, Caiyun Yu, Xinying Zhang, Xuesen Fan
Summary: The efficient and unprecedented synthesis of indolyl-tethered spiro[cyclobutane-1,1'-indenes] was achieved through the cascade reaction of 1-(pyridin-2-yl)-1H-indoles with alkynyl cyclobutanols. Mechanistic experiments revealed a sequential process involving alkenylation and intramolecular Friedel-Crafts reaction. This novel protocol demonstrated high substrate scope, chemo- and regioselectivity, removable directing group, and scalability, with the resulting product being easily derivatized further.
Article
Chemistry, Multidisciplinary
Isaac Choi, Antonis M. Messinis, Xiaoyan Hou, Lutz Ackermann
Summary: The research reveals osmaelectrocatalyzed C-H activations using benzoic acids, enabling electrooxidative alkyne annulations with high levels of selectivity. Unprecedented osmium(0) and osmium(II) intermediates were isolated, and detailed mechanistic studies unveiled a facile C-H cleavage and ample substrate scope for annulated heterocycles synthesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Elmira Meghrazi Ahadi, Alireza Abbasi Kejani, Hormoz Khosravi, Vaezeh Fathi Vaysari, Saeed Balalaie, Frank Rominger, Hamid Reza Bijanzadeh
Summary: Practical Pd-catalyzed 2-pyridones were designed to synthesize chromeno[2,3-b]pyridine-2-ones through domino nucleophilic addition and decarboxylative arylation. This methodology offers an efficient approach to construct bioactive fused-heterocyclic skeletons in a single step with high selectivity and good yields.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Yueyao Feng, Jie Wang, Jie Yang, Fengyuan Chen, Zemin Zhang, Chongrong Ke, Jin Lin, Hua Lin
Summary: Selective remote C-H activation of amines using unmodified NH2 as a directing group is synthetically valuable. The selective iodination of 3-arylpropan-1-amines provides valuable intermediates for modifying bioactive molecules and synthesizing quinolones. This study reports the first palladium-catalyzed selective epsilon-C(sp(2))-H iodination of free 3-arylpropan-1-amines via a seven-membered palladacycle.
Article
Energy & Fuels
Xuandong Liu, Lei Li, Huayang Sun, Guangming Wen, Dan Wang, Shenyong Ren, Qiaoxia Guo, Wencheng Zhang, Shengbao He, Baojian Shen
Summary: The incorporation of C12A7-H- in NiW catalysts enhances the reaction rate constants and turnover frequencies in the hydrodesulfurization of dibenzothiophene. This is due to the promotion of reducibility and increased sulfidation degree by C12A7-H-, leading to higher hydrogenation selectivity despite a decrease in rim/edge sites ratios and Lewis acid sites. Furthermore, C12A7-H- modified NiW catalysts also exhibit higher HDS rates in 4,6-dimethyldibenzothiophene, attributed to the transfer of active hydrogen species and promotion of hydrogenation selectivity.
Review
Chemistry, Organic
Nelson Y. S. Lam, Ian Paterson
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Chemistry, Multidisciplinary
Guangrong Meng, Nelson Y. S. Lam, Erika L. Lucas, Tyler G. Saint-Denis, Pritha Verma, Nikita Chekshin, Jin-Quan Yu
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Review
Chemistry, Multidisciplinary
Nelson Y. S. Lam, Kevin Wu, Jin-Quan Yu
Summary: The design of synthetic routes by retrosynthetic logic is influenced by available transformations. Transition-metal-catalyzed C-H activation is a powerful strategy for C-C bond formation, but its uptake in total synthesis has been tepid due to synthetic intractability and a lack of comprehensive guidelines. This Review addresses these issues and offers a guide to identify retrosynthetic opportunities to generate C-C bonds by C-H activation processes. Comparing traditional approaches and recent C-H activation methods, this Review demonstrates more efficient retrosynthetic strategies enabled by C-H activation for C-C bond construction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Tyler G. Saint-Denis, Nelson Y. S. Lam, Nikita Chekshin, Paul F. Richardson, Jason S. Chen, Jeff Elleraas, Kevin D. Hesp, Daniel C. Schmitt, Yajing Lian, Chan Woo Huh, Jin-Quan Yu
Summary: Enantioselective C(sp(3))-H activation has attracted significant interest, but the mechanisms responsible for enantioselection remain unclear. This study found extreme sensitivity differences in two substrate classes, leading to high enantiomeric ratios for thioether-directed-C(sp(3))-H arylation. The exploitation of transient chirality at sulfur was key to achieving stereochemical information transfer from ligand backbone to substrate carbons.
Review
Chemistry, Multidisciplinary
Erika L. Lucas, Nelson Y. S. Lam, Zhe Zhuang, Hau Sun Sam Chan, Daniel A. Strassfeld, Jin-Quan Yu
Summary: CONSPECTUS: The development of asymmetric beta-C-H activation reactions for organic synthesis has been described in this Account. By studying reaction mechanisms and stereochemical properties, both strongly coordinating and weakly coordinating directing groups were designed to achieve beta-C-H activation of aliphatic acids and carboxylic acids, respectively. The development of five classes of chiral ligands enabled enantioselective beta-C-H activation reactions of readily available substrates.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Dianna Truong, Nelson Y. S. Lam, Meder Kamalov, Mie Riisom, Stephen M. F. Jamieson, Paul W. R. Harris, Margaret A. Brimble, Nils Metzler-Nolte, Christian G. Hartinger
Summary: The study presents a novel approach for selectively anchoring transition metal half-sandwich complexes onto peptides with high purity using solid support synthesis. The metalated peptides were evaluated for their anticancer properties against human cancer cell lines, showing no cytotoxic activity but potential for site-selective peptide labelling and ligand design in transition metal catalysts.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Nelson Y. S. Lam, Zhoulong Fan, Kevin Wu, Han Seul Park, Su Yong Shim, Daniel A. Strassfeld, Jin-Quan Yu
Summary: This study summarizes key factors for achieving high selectivity at defined aryl positions by analyzing 119 structurally unique remote DTs, which are experimentally corroborated through the development of new aliphatic meta and para-selective DTs for electronically unbiased arenes. These empirical rules, summarizing key distance and geometric factors, are expected to be useful tools for the future development of site-selective arene C-H activation and other reactions relying on covalent/noncovalent DT-mediated remote regioselection.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Chemistry, Organic
Nelson Y. S. Lam, Ian Paterson
Summary: This Review summarizes the ongoing synthetic efforts and NMR studies on hemicalide, a marine natural product with potent anticancer activity. By reducing the number of possible stereoisomers and establishing a more manageable number of structures, it sets the stage for a focused total synthesis campaign.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Robert Pearce-Higgins, Larissa N. Hogenhout, Philip J. Docherty, David M. Whalley, Padon Chuentragool, Najung Lee, Nelson Y. S. Lam, Thomas M. McGuire, Damien Valette, Robert J. Phipps
Summary: Axial chirality is important in molecules of biological interest and chiral catalyst designs. Atropisomeric 2,2'-biphenols are commonly found, and their synthesis with enantioenrichment is desirable. By using enantiopure, sulfonated SPhos (sSPhos), a ligand with an atropisomeric axis introduced through sulfonation, a practical separation method is developed to access enantioenriched biphenols. The high levels of asymmetric induction obtained in the Suzuki-Miyaura coupling reaction may be attributed to attractive noncovalent interactions involving the ligand sulfonate group.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Zhoulong Fan, Xiangyang Chen, Keita Tanaka, Han Seul Park, Nelson Y. S. Lam, Jonathan J. Wong, K. N. Houk, Jin-Quan Yu
Summary: This study presents two distinct directing templates that allow for the differentiation and functionalization of remote and similar positions on bicyclic aza-arenes. This strategy enables site-selective C-H olefination, alkynylation, and allylation reactions on quinoline-containing compounds, and can be performed in a modular fashion in different orders.
Article
Chemistry, Multidisciplinary
Tegan P. Stockdale, Nelson Y. S. Lam, Ian Paterson
Summary: By targeted synthesis of fragments and detailed NMR spectroscopic analysis, the stereochemical elucidation of a portion of the cytotoxic polyketide hemicalide is achieved, reducing the number of possible structural permutations to eight diastereomers.
CHEMICAL COMMUNICATIONS
(2022)
Review
Chemistry, Multidisciplinary
Nelson Y. S. Lam, Tegan P. Stockdale, Matthew J. Anketell, Ian Paterson
Summary: This article explores innovative strategies for the chemical synthesis of macrolide natural products and reflects on the challenges and discoveries encountered during the total synthesis process in the laboratory. By synthesizing six representative macrolide natural products, researchers propose efficient methods for the construction of these valuable compounds.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Ikenna E. Ndukwe, Xiao Wang, Nelson Y. S. Lam, Kristaps Ermanis, Kelsey L. Alexander, Matthew J. Bertin, Gary E. Martin, Garrett Muir, Ian Paterson, Robert Britton, Jonathan M. Goodman, Eric J. N. Helfrich, Joern Piel, William H. Gerwick, R. Thomas Williamson
CHEMICAL COMMUNICATIONS
(2020)
Article
Chemistry, Multidisciplinary
Talia R. Pettigrew, Rachel J. Porter, Stephen J. Walsh, Michael P. Housden, Nelson Y. S. Lam, Jason S. Carroll, Jeremy S. Parker, David R. Spring, Ian Paterson
CHEMICAL COMMUNICATIONS
(2020)