Article
Chemistry, Multidisciplinary
Dominik Lichte, Nico Pirkl, Gregor Heinrich, Sayan Dutta, Jonas F. Goebel, Debasis Koley, Lukas J. Goossen
Summary: This study demonstrates the achievement of para-C-H arylation of non-activated aryl halides with anilines using a base-assisted metalla-tautomerism approach. The challenge of directing functionalization towards the furthest C-H group has been overcome.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Md. Emdadul Hoque, Jin-Quan Yu
Summary: In this study, we report a new method for the gamma-arylation and gamma-lactonization of aliphatic acids, enabled by a L,X-type CarboxPyridone ligand catalyzed Pd(II) reaction. A wide range of gamma-arylated gamma-lactones can be efficiently synthesized in a single step, and the arylated lactones can be further converted into disubstituted tetrahydrofurans, which are prominent scaffolds in bioactive molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Hou-ji Cao, Meng Chen, Fangxiang Sun, Yue Zhao, Changsheng Lu, Xiaolei Zhang, Zhuangzhi Shi, Hong Yan
Summary: The development of regioselective poly-arylation of o-, m-, and p-carboranes using an imine-directed, Pd-catalyzed iterative B-H activation method has been described. The study isolated key palladium intermediates and found that the steric factor of introduced aryl groups affects metal selectivity and chelation mode. Furthermore, a series of cage B(3,4,5,6)-tetraarylated o-carboranes and B(2,3,4,5,6)-penta-arylated m- and p-carboranes were synthesized as a new type of molecular propellers.
Article
Chemistry, Multidisciplinary
Anton Kudashev, Olivier Baudoin
Summary: A ligand-controlled site-selective C(sp(3))-H arylation of heteroaromatic ketones has been developed using Pd catalysis, with selective reactions occurring at the alpha- or beta-position of the ketone side-chain. Addition of a pyridone ligand enables switching from alpha- to beta-arylation. The alpha-arylation process demonstrates broad scope and high site- and chemoselectivity, while the beta-arylation is more limited, with mechanistic investigations suggesting different pathways for the two processes.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Jyoti Dhankhar, Micha D. Hofer, Anthony Linden, Ilija Coric
Summary: This article presents a new selectivity mode for C-H arylation reactions, which is the preference for C(sp(2))-H activation next to alkyl groups. The study results indicate that this preference is related to the non-covalent interactions between the catalyst and the substrate.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Verena Sukowski, Manuela van Borselen, Simon Mathew, M. Angeles Fernandez-Ibanez
Summary: By reversing conventional site-selectivity of C-H activation, a new catalytic system based on palladium/norbornene and an S,O-ligand for meta-C-H arylation of aryl ethers is reported, which outperforms previously reported systems. This system shows unique ability to use alkoxyarene substrates with different substituents, as well as tolerate ortho-substituted aryl ethers by employing novel norbornene mediators. Moreover, monoarylation of alkoxyarenes is achieved for the first time, enabling rapid introduction of a second, different aryl coupling partner.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Jin-Tang Cheng, Li-Jun Xiao, Shao-Qun Qian, Zhe Zhuang, An Liu, Jin-Quan Yu
Summary: In this study, we report the first example of selective Pd(II)-catalyzed tertiary C-H activation of cyclobutylmethyl ketones using a transient directing group. An electron-deficient 2-pyridone ligand was identified as the optimal external ligand to achieve tertiary C-H activation. Various cyclobutylmethyl ketones with quaternary carbon centers were obtained in high yields without the need for preinstalling internal directing groups, and showed high regioselectivity for tertiary C-H arylation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Zengbing Bai, Qingqing Chen, Jun Gu, Chuangxu Cai, Jie Zheng, Wangjian Sheng, Shandong Yi, Fang Liu, Huan Wang
Summary: The paper introduces a versatile strategy based on late-stage palladium-catalyzed C-H activation for synthesizing peptides with backbone thiazole motifs, enabling site-selective arylation in peptide side chains and expanding the structural diversity of peptide compounds. This method exhibits high biocompatibility and is capable of efficiently constructing peptide libraries with featured backbone thiazole units.
Article
Chemistry, Organic
Hyeonbin Ha, Ho Jeong Choi, Hahyoun Park, Yunyeong Gwon, Jiin Lee, Jaesung Kwak, Min Kim, Byunghyuck Jung
Summary: The research reveals the use of 3-bromo-2-hydroxybenzaldehyde as a transient directing group in the Pd-catalyzed gamma-position sp(3)-C-H arylation of primary amines, and detailed the reaction mechanism and high selectivity origins through density functional theory calculations and X-ray crystal structure analysis.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Philip A. Provencher, Katherine L. Bay, John F. Hoskin, K. N. Houk, Jin-Quan Yu, Erik J. Sorensen
Summary: This study presents a Pd(II)-catalyzed method for cyclative C(sp(3))-H arylation of ketones, utilizing a transient directing group. By carefully selecting reaction conditions and the directing group, the researchers were able to enhance selectivity and yield, facilitating the arylation reaction to occur.
Article
Chemistry, Multidisciplinary
Guangrong Meng, Liang Hu, Martin Tomanik, Jin-Quan Yu
Summary: Pd-II-catalyzed beta- and gamma-C(sp(3))-H heteroarylation of free carboxylic acids using pyridine-pyridone ligands overcomes limitations in selective functionalization and compatibility with heteroatoms. A sequence of three consecutive C(sp(3))-H activation reactions of pivalic acid constructs diverse quaternary carbon centers containing heteroaryls, offering a valuable tool for breaking new ground in medicinal chemistry.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Filip Horky, Ivana Cisarova, Petr Stepnicka
Summary: This study described the synthesis of new donor-unsymmetric dppf congeners and their conversion into air-stable Pd(0) complexes, which showed high catalytic activity and selectivity in the Pd-catalyzed C-H arylation reaction. The complex [Pd(ma)(2)] performed the best in synthesizing 2-arylbenzoxazoles with high yield and selectivity under environmentally friendly conditions.
Article
Chemistry, Multidisciplinary
Max J. Caplin, Daniel J. Foley
Summary: Fragment-based drug discovery is a crucial technology for delivering clinical candidates, but the development of sp(3)-rich fragments remains challenging. Recent advances in C(sp(3))-H functionalization offer valuable approaches to advancing fragment hits by 'growing' functionalized rings and chains from unconventional, carbon-centered vectors.
Article
Chemistry, Physical
Cintya Pinilla, Vanesa Salamanca, Agusti Lledos, Ana C. Albeniz
Summary: Metal-catalyzed C-H functionalizations on the aryl ring of anilines usually require cumbersome N-protection-deprotection strategies for chemoselectivity. In this study, we demonstrate a Pd-catalyzed direct C-H arylation of unprotected anilines with no competition from N-arylation product. The ligand [2,2'-bipyridin]-6(1H)-one drives the chemoselectivity by kinetic differentiation in the product-forming step while aiding in the C-H cleavage step. The deprotonation of the NH moiety in an anionic intermediate favors regioselectivity towards ortho substitution.
Article
Chemistry, Physical
Yi-Hao Li, Yuxin Ouyang, Nikita Chekshin, Jin-Quan Yu
Summary: Pd(II)-catalyzed gamma-C(sp3)-H (hetero)arylation of aliphatic ketones using alpha-amino acids as transient directing groups (TDG) has been developed. By reducing the loading of acid additives, the crucial ligand effect of 2-pyridone is enhanced, leading to improved reactivity and the possibility of cyclic gamma-methylene C(sp3)-H arylation of ketones. Mechanistic investigation and comparison to the gamma-C-H arylation of aldehydes provide structural insights for designing site-selective TDGs.
Article
Chemistry, Multidisciplinary
Hao Wang, Yuzhen Gao, Chunlin Zhou, Gang Li
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Chemistry, Multidisciplinary
Zhuomin Chi, Yuzhen Gao, Lei Yang, Chunlin Zhou, Meng Zhang, Peiming Cheng, Gang Li
Summary: A visible-light-induced spirocyclizative hydroarylation via reductive dearomatization of non-activated arenes, including 2-phenyl indoles and naphthalene derivatives, is described. This protocol allows for the rapid synthesis of valuable spirocycles with carbon-carbon double bonds from readily accessible aromatic precursors in a single step.
CHINESE CHEMICAL LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Shangda Li, Chunhui Zhang, Lei Fu, Hang Wang, Lei Cai, Xiaoxi Chen, Xinchao Wang, Gang Li
Summary: Metathesis reactions are powerful synthetic tools used in various fields. In this study, the first Pd(II)-catalyzed C-H iodination of arenes was reported, using 2-nitrophenyl iodides as iodinating reagents via a formal metathesis reaction. The reaction exhibited unusual C-I bond formation instead of C-C coupling, allowing for selective iodination of challenging substrates.
Article
Chemistry, Multidisciplinary
Yuzhen Gao, Hao Wang, Zhuomin Chi, Lei Yang, Chunlin Zhou, Gang Li
Summary: In this paper, a novel strategy for visible-light-induced spirocyclizative remote arylcarboxylation of nonactivated arenes is reported. This transformation, achieved through a radical-polar crossover cascade, allows for the rapid synthesis of diverse spirocyclic and carboxylic acid derivatives from readily accessible aromatic precursors.
Article
Chemistry, Organic
Ning Wang, Zhuomin Chi, Xinchao Wang, Zezhong Gao, Shangda Li, Gang Li
Summary: Functional group metathesis has the potential to provide mild reaction conditions for C-H functionalization. This study reports the meta- and ortho-C-H iodination of aniline derivatives using 2-nitrophenyl iodides as mild iodinating reagents. The results demonstrate the potential for developing novel site-selective C-H activation reactions with electron-rich compounds using mild reagents.
Article
Chemistry, Organic
Zezhong Gao, Hang Wang, Chunlin Zhou, Ning Wang, Shangda Li, Gang Li
Summary: In this study, a new C-H functionalization method was reported for the remote site-selective C-H iodination via C(sp(2))-H/C(sp(2))-I metathesis. The mild iodinating reagent, 1-iodo-4-methoxy-2-nitrobenzene, was used to iodinate 2-aryl benzoic acid derivatives, including 2-(naphthalen-1-yl)benzoic acids and [1,1'-binaphthalene]-2-carboxylic acids, giving valuable iodinated products in a site- and chemo-selective manner.
Article
Chemistry, Physical
Hang Wang, Huiling Li, Xiahe Chen, Chunlin Zhou, Shangda Li, Yun-Fang Yang, Gang Li
Summary: In this study, a chiral ligand-controlled, asymmetric remote meta-C-H activation method was reported. By using a specific chiral ligand and Pd(II) catalyst, asymmetric C-H olefination and arylation of arenes were achieved. The origins of enantioselectivity were explained through density functional theory calculations.
Article
Chemistry, Multidisciplinary
Hong Lv, Xinchao Wang, Yanzhao Hao, Chao Ma, Shangda Li, Gang Li, Jian Zhang
Summary: A new method for carboxylation of unactivated sp(2) C-H bonds with CO2 was reported using a rhodium catalyst, generating a series of ferrocene-embedded lactones that are important molecular skeletons in pharmaceuticals and ligands. The first example of asymmetric C-H carboxylation with CO2 was achieved with a chiral NHC ligand, demonstrating moderate enantioselectivity. Preliminary mechanistic experiments revealed bivalent rhodium as the active catalyst, and a reasonable catalytic cycle was proposed.
Article
Chemistry, Multidisciplinary
Hang Wang, Chunlin Zhou, Zezhong Gao, Shangda Li, Gang Li
Summary: In this study, a highly enantioselective isodesmic C-H functionalization method was developed to access chiral iodinated phenylacetic Weinreb amides via desymmetrization and kinetic resolution with Pd-II catalysis. The rapid synthesis of chiral aromatic iodides is of significant importance for synthetic chemistry, and further transformations of the enantioenriched products are readily available, opening up new possibilities for related studies in synthetic and medicinal chemistry.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Lei Yang, Xinchao Wang, Meng Zhang, Shangda Li, Xinqiang Fang, Gang Li
Summary: This study reports a Pd-catalyzed remote isodesmic meta-C-H iodination of phenethylamines, benzylamines, and 2-aryl anilines using 1-iodo-4-methoxy-2-nitrobenzene as the mild iodinating reagent. A range of valuable meta-iodinated and even multi-halogenated amines were successfully synthesized, paving the way for synthetic chemists to access various amine derivatives at the challenging meta-positions.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Physical
Hang Wang, Huiling Li, Xiahe Chen, Chunlin Zhou, Shangda Li, Yun-Fang Yang, Gang Li
Summary: The use of a chiral ligand-controlled, asymmetric remote meta-C-H activation enables asymmetric C-H olefination and arylation of hydrocinnamic acid derivatives. The origins of the enantioselectivity were explained using density functional theory calculations.
Article
Chemistry, Multidisciplinary
Hao Wang, Lei Fu, Chunlin Zhou, Gang Li
Summary: The newly developed Pd-catalyzed meta-C-H bromination of aniline derivatives overcomes the ortho/para selectivity competition in electrophilic bromination, with the addition of acid additives crucial for reaction success. A broad range of substrates and benzoic acid derivatives with complex substitution patterns are applicable, with the potential for C-H chlorination under similar conditions.
Article
Chemistry, Multidisciplinary
Chunlin Zhou, Xinchao Wang, Lei Yang, Lei Fu, Gang Li
Summary: This study reports a method of using light to drive a regioselective carbocarboxylation reaction between CO2 and aryl and alkyl halides. This method allows for the rapid and highly regioselective synthesis of complex β,γ-unsaturated carboxylic acids.
Article
Chemistry, Multidisciplinary
Xinchao Wang, Hang Wang, Chunlin Zhou, Lei Yang, Lei Fu, Gang Li
Summary: This study presents a method of employing a native directing group for C-H activation, specifically focusing on the ortho-C-H acetoxylation of hydrocinnamic and phenylacetic acids, which are key moieties in many biologically active molecules. The broad scope and potential application of this reaction, as demonstrated with drug molecules, indicate its promising utility in future synthetic endeavors.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Xiaoxi Chen, Shuai Fan, Meng Zhang, Yuzhen Gao, Shangda Li, Gang Li
Summary: An unprecedented pyridine-based para-directing template (DT) assisted, Pd-catalyzed para-C-H alkenylation of three classes of arenes was reported, which allows for easy synthesis and recycling under mild conditions. This method offers a new approach for the rapid construction of para-substituted arenes.