Article
Chemistry, Multidisciplinary
Daigo Hayashi, Tomohiro Tsuda, Ryo Shintani
Summary: A palladium-catalyzed skeletal rearrangement has been developed to synthesize highly fused tetrahydrophenanthrosilole derivatives via bond exchange. The reaction conditions can be tuned to produce different products, fused dihydrodibenzosilepin derivatives.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Bidhan Ghosh, Satabdi Bera, Pintu Ghosh, Rajarshi Samanta
Summary: An efficient Rh(iii)-catalyzed strategy has been developed for the synthesis of quinoline braced cyclophane macrocycles via methyl (sp(3)) C-H functionalization, which is mild, simple, regioselective, and tolerates various functional groups with different ring sizes. The method involves C8-methyl metalation, metal-carbene formation, and migratory insertion, with high dilution not necessary and nitrogen being the only byproduct. Preliminary investigation suggests that the C-H metalation step is the rate-determining step.
CHEMICAL COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Meng-Yue Wang, Xue-Qing Zhu, Bao-Yin Zhao, Hong-Xia Zhang, Yong-Qiang Wang, Qiong Jia
Summary: In this study, the first palladium-catalyzed intramolecular C-H/C-H dehydrogenative coupling reaction of two simple arenes was reported to generate 5,6-dihydrophenanthridines. This approach has a wide substrate scope and good tolerance of functional groups, providing an efficient alternative synthesis route for important 5,6-dihydrophenanthridine compounds.
Article
Chemistry, Multidisciplinary
Han Gao, Lingfei Hu, Yanlei Hu, Xiangying Lv, Yan-Bo Wu, Gang Lu
Summary: The origins of regioselectivity in Ni-catalyzed alkene hydrofunctionalizations were computationally investigated using energy decomposition analysis. The results indicate that the Markovnikov selectivity with aryl-substituted alkenes is favored due to the stabilizing charge transfer effect, while the anti-Markovnikov selectivity with alkyl-substituted alkenes is favored because of the destabilizing Pauli repulsion effect.
CHEMICAL COMMUNICATIONS
(2022)
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
Yusuke Ano, Daichi Takahashi, Yuki Yamada, Naoto Chatani
Summary: The palladium-catalyzed skeletal rearrangement of 3-arylcyclobutanones into 1-indanones is achieved using a Pd(0)/IMes catalyst. The reaction occurs via cleavage of C(carbonyl)-C(sp3) and C(sp2)-H bonds, without the need for an extra reactive functional group or a directing group. Deuterium-labeling experiments indicate that the C-C bond activation is the initial step, followed by rate-determining C-H activation.
Article
Chemistry, Applied
Su Chen, Monica Oliva, Luc Van Meervelt, Erik V. Van der Eycken, Upendra K. Sharma
Summary: The study presents a palladium-catalyzed cascade reaction to construct difunctionalized acyl indoles, involving multiple bond formations in a single operational step. Enantioselectivity at a quaternary carbon center is attempted. Additionally, a continuous-flow process is demonstrated for the synthesis of aryl isocyanides within minutes and their telescopic use.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Liwei Zhou, Shujia Qiao, Fengru Zhou, Xinyu Xuchen, Guobo Deng, Yuan Yang, Yun Liang
Summary: A novel palladium-catalyzed decarboxylative cascade cyclization for the assembly of diverse fused heteropolycycles has been reported. The approach enables the simultaneous construction of six- and seven-membered rings via intramolecular carbopalladation, C-H activation, and decarboxylation.
Article
Chemistry, Applied
Li-Yun Guo, Qing Li, Yu-Tao Liu, Lin Li, Yu-Qing Ni, Yang Li, Fei Pan
Summary: A palladium-catalyzed method for direct alkynylation of unactivated alkenes via C-H activation, assisted by 8-aminoquinoline, has been successfully developed. This method is applicable to both internal and terminal unactivated alkenes, showing broad functionality tolerance, good regio- and diastereoselectivity, and providing an alternative approach for constructing conjugated 1,3-enynes.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Qikai Sun, Huixing Zhang, Quanquan Wang, Tianjiao Qiao, Gang He, Gong Chen
Summary: A new strategy has been developed for the stereoselective synthesis of C-vinyl glycosides, using Pd-catalyzed directed C-H glycosylation. This method offers a broadly applicable approach to streamline the synthesis of complex C-vinyl glycosides with high efficiency and excellent regio- and stereoselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Nahiane Pipaon Fernandez, Gregory Gaube, Kyla J. Woelk, Mathias Burns, Damian P. Hruszkewycz, David C. Leitch
Summary: We present a new method for direct C-C bond formation using tandem C-O/C-H activation mediated by palladium catalyst. This approach allows for base-free direct C-H alkenylation by combining C-O oxidative addition at enol pivalates and concerted metalation-deprotonation of functionalized heterocycles. Mechanistic studies show that C-O oxidative addition is reversible and C-H activation occurs directly from the Pd(II) C-O oxidative addition product. In situ P-31 NMR spectroscopy reveals that (Cy3P)(2)Pd-(alkenyl)(OPiv) species is the predominant catalyst resting state during the reactions.
Article
Chemistry, Multidisciplinary
Rie Yoshimoto, Attila Taborosi, Qiyuan He, Yusuke Ano, Naoto Chatani, Seiji Mori
Summary: The reaction between aromatic amides and maleimides, catalyzed by palladium, leads to the formation of a product with double C-H bond activation, occurring at both the benzylic and meta positions. Computational chemistry studies reveal a stepwise mechanism involving a six-membered palladacycle, maleimide insertion, protonation of the Pd-N bond, and activation of the meta C-H bond. The site selectivity is determined by the interaction energy controlling the insertion of maleimide into the Pd-C(sp(3)) bond. The meta C-H bond activation step is identified as the rate-determining step based on the energetic span model. The 2-thiomethylphenyl group is found to function effectively as a directing group due to strong Pd-S bonding and the destabilizing effect of the deformation energy.
CHEMISTRY-AN ASIAN JOURNAL
(2023)
Article
Chemistry, Organic
Jian Zhang, Xinzhe Shi, Henri Doucet
Summary: This study explores a Pd-catalyzed annulative pi-extension reaction of 1-arylpyrroles using 1,2-dihalobenzenes as coupling partners, leading to the selective synthesis of pyrrolo[1,2-f]phenanthridines. The higher reactivity of the pyrrole C2-H bond allows for successful access to substituted pyrrolo[1,2-f]phenanthridines.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Ge Zhang, Xiao-Jiao Feng, Meng-Yao Li, Xiao-Ming Ji, Guo-Qiang Lin, Chen-Guo Feng
Summary: A Pd-catalyzed synthesis of tetrasubstituted allenes from aryl bromides and aryl diazoacetates has been developed. The reaction proceeds via an aryl to alkenyl transformation, involving 1,4-palladium migration, carbene insertion, and β-H elimination under mild reaction conditions.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Qiyuan He, Naoto Chatani
Summary: The palladium-catalyzed [3+2] annulation of aromatic amides with maleimides via the activation of ortho benzylic C-H and meta C-H bonds is reported, with a key role played by the presence of a 2-methylthiophenyl directing group for the success of the reaction. The irreversible cleavage of these C-H bonds leads to the formation of five-membered cyclic products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Ramon Arora, Jose F. Rodriguez, Andrew Whyte, Mark Lautens
Summary: A palladium-catalyzed strategy has been proposed for synthesizing unsymmetrically linked heterocycles within stereoselective tetrasubstituted olefins, with high yields and excellent stereoselectivities achieved using low catalyst loadings. Mechanistic studies suggest a syn-carbopalladation of the carbamoyl chloride followed by Pd-II-catalyzed cyclization of alkyne-tethered nucleophiles.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Austin D. Marchese, Andrew G. Durant, Mark Lautens
Summary: A simple and modular approach using palladium catalysis to synthesize bis-heterocyclic spirocycles is reported. The method leverages a Mizoroki-Heck-type reaction to generate neopentylpalladium species, allowing for intramolecular C-H activation on a wide array of C-H bonds to produce a variety of spirocycles. The reaction is scalable, allowing for easy incorporation of biologically relevant heterocycles without the need for flash column chromatography.
Article
Chemistry, Multidisciplinary
Austin D. Marchese, Bijan Mirabi, Colton E. Johnson, Mark Lautens
Summary: This paper reports a comprehensive study of reversible C-C bond formation using palladium catalysis. It was found that different diastereomers can be converted to the same product under identical catalytic conditions. Experimental and computational studies also investigated key concepts such as the effect of electronic and steric parameters on the C-C bond cleavage step.
Article
Chemistry, Physical
Abdoul G. Diallo, Deborah Paris, Djiby Faye, Sylvain Gaillard, Mark Lautens, Jean-Luc Renaud
Summary: This study reports a general approach for the allylation of oxa- and azabenzonorbornadienes by merging organophotoredox and nickel catalysis. The method allows for selective allylation of various heterocyclic alkene derivatives with a broader range of allylic acetate compounds. Notably, the reaction does not require air-sensitive organometallic species or metal reductants.
Article
Chemistry, Multidisciplinary
Austin D. Marchese, Andrew G. Durant, Cian M. Reid, Clara Jans, Ramon Arora, Mark Lautens
Summary: A Pd(0)/blue light catalyzed carboiodination reaction has been reported, which generates a variety of iodinated hetero- and carbocycles. The reaction system is simple and stable, and shows good tolerance towards sensitive functional groups, delivering products in high yields. Experimental evidence supports the reversible C-I bond formation via a single electron mechanism.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Mark Lautens, Egor M. Larin, Jeanne Masson-Makdissi, Jin Jang
Summary: In this study, a rhodium-catalyzed domino strategy was developed for the synthesis of oxindole-containing products from simple ortho-bromoaniline-derived acrylamides. Mechanistic and computational studies elucidated that the reaction proceeds through a Heck-type process to generate benzylidene intermediate and subsequent beta-hydride elimination, followed by the formation of RhI-hydride species and a 1,4-conjugate addition to yield the final oxindole products. Importantly, the use of sodium formate was found to be crucial for generating the rhodium hydride species and enabling the catalyst turnover.
Review
Chemistry, Organic
Austin D. D. Marchese, Bijan Mirabi, Mark Lautens
Summary: The activation of C-C bonds via transition metal catalysis has gained popularity in organic synthesis. Rhodium or palladium catalysis is being used to facilitate beta-carbon elimination, which relies on thermodynamic driving forces such as relief of ring or steric strain. This review focuses on recent applications of beta-carbon eliminations under palladium and rhodium catalysis.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Multidisciplinary
E. Ali McKnight, Ramon Arora, Ekadashi Pradhan, Yuriko H. Fujisato, Ayonitemi J. Ajayi, Mark Lautens, Tao Zeng, Christine M. M. Le
Summary: A BF3-catalyzed atom-economical fluorocarbamoylation reaction was reported, which enables the insertion of alkynes into strong C-F bonds through a halide recycling mechanism. The developed method provides stereoselective access to 3-(fluoromethylene) oxindoles and gamma-lactams, including fluorinated derivatives of known protein kinase inhibitors. Experimental and computational studies support a stepwise mechanism for the fluorocarbamoylation reaction involving a cyclization step followed by internal fluoride transfer.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Sean Harrington, Jacob Pyche, Andrew R. Burns, Tina Spalholz, Kaetlyn T. Ryan, Rachel J. Baker, Justin Ching, Lucien Rufener, Mark Lautens, Daniel Kulke, Alexandre Vernudachi, Mostafa Zamanian, Winnie Deuther-Conrad, Peter Brust, Peter J. Roy
Summary: Nematode parasites of humans and livestock are a significant burden to human health, economic development, and food security. The discovery of Nemacol, a novel anthelmintic drug, provides a potential solution to the problem of drug resistance and lack of effective treatments for nematode parasites. Nemacol inhibits the vesicular acetylcholine transporter (VAChT) and enhances the efficacy of existing anthelmintic drugs.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Ramon Arora, Regina M. Oechsner, Clara Jans, Bijan Mirabi, Austin D. Marchese, Mark Lautens
Summary: A palladium-catalyzed epimerization reaction of stereogenic alkyl iodides is reported using an air-stable precatalyst. Mechanistic experiments revealed the stereoinversion of the C-I bond via reversible bond formation, supported by density functional theory studies. Stoichiometric experiments showed that irradiation of isolable alkyl-Pd(II) complexes promoted C-I reductive elimination, with potential application in C-Br bond formation.
Article
Chemistry, Multidisciplinary
Eric N. Donders, Kai V. Slaughter, Christian Dank, Ahil N. Ganesh, Brian K. Shoichet, Mark Lautens, Molly S. Shoichet
Summary: The pK(a) of colloid-forming drugs can be manipulated to achieve endosomal disruption while avoiding phospholipidosis and minimizing toxicity, leading to the design of drug-rich nanoparticles. By synthesizing ionizable derivatives of fulvestrant analogs, which are lipid-stabilized drug colloids, the pK(a) of these ionizable colloids influenced the mechanism of endosomal and lysosomal disruption. This study establishes a tunable and generalizable strategy for endosomal disruption by manipulating the pK(a) of colloid-forming drugs.
Article
Chemistry, Organic
Jonathan Bajohr, Aureilien Dupeux, Daniel Schenk, Clara Jans, Mark Lautens
Summary: The synthesis of bis-heterocyclic spirocycles containing pyrroline and indoline motifs through palladium-catalyzed reactions is reported. In situ generation of palladacycles via Narasaka-Heck/C-H activation reactions using di-tert-butyldiaziridinone as a functionalizing reagent. The scalability of the reaction and the synthetic utility of the spirocyclic products are demonstrated through their deprotection, reduction, and (3 + 2) cycloaddition reactions. Kinetic isotope effect experiments provide evidence for a turnover-limiting C-H functionalization step in the catalytic cycle.
Article
Chemistry, Multidisciplinary
Xavier Abel-Snape, Colton E. Johnson, Bianca Imbriaco, Mark Lautens
Summary: A palladium-catalyzed spirocyclization reaction was reported, which involved the insertion of an oxabicycle into a palladacycle. The reaction proceeded via carbocyclization and a C-H functionalization sequence, and the diastereoselective nature of the insertion was observed. The spirooxindoles produced in the reaction allowed for further transformations and were previously unaccessible.
Article
Chemistry, Organic
Colton E. Johnson, Shangyu Li, Ramon Arora, Bijan Mirabi, Mark Lautens
Summary: This article focuses on the mechanism, recent applications, challenges, and outlook of Ni-catalyzed C-H activation of sp(3)-hybridized carbon atoms. The study highlights the differences between Ni and Pd in C-H activation and discusses the choice of directing groups as well as primary, secondary, and tertiary C-H activation.
