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
Arnab Dey, Anurag Singh, Chandra M. R. Volla
Summary: The efficient oxidative [3 + 2] annulation reaction of aryl hydrazones and heterobicyclic alkenes has been achieved using inexpensive cobalt salts under aerobic conditions. The reaction generates complex indane derivatives with high anti-diastereoselectivity, avoiding the use of stoichiometric amounts of metal oxidants.
CHEMICAL COMMUNICATIONS
(2022)
Review
Chemistry, Organic
Austin Pounder, Eric Neufeld, Peter Myler, William Tam
Summary: This review provides a comprehensive overview of transition-metal-catalyzed domino reactions of strained bicyclic alkenes, including both homo- and heterobicyclic alkenes. These compounds serve as important building blocks in organic synthesis, enabling the construction of biologically/medicinally relevant compounds with multiple stereocenters. The review is categorized based on the metal used in the reaction, and discusses the substrate scope, reaction conditions, and potential applications in organic synthesis. It also presents a comprehensive outlook on the reactivity paradigms of homo- and heterobicyclic alkenes, offering insights into future directions for further advancement in this field.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Bo Wei, Taylor A. Hatridge, Christopher W. Jones, Huw M. L. Davies
Summary: A tandem system incorporating in-line diazo compound synthesis and downstream consumption in a rhodium-catalyzed cyclopropanation reaction has been developed for the synthesis of 1,2-diarylcydopropane-1-carboxylates in high yields and with high levels of enantioselectivity. The flow to batch method allows for direct elution of crude aryldiazoacetate into the cyclopropanation reaction, catalyzed by chiral dirhodium tetracarboxylates Rh-2(R-p-Ph-TPCP)(4) and Rh-2(R-PTAD)(4).
Article
Chemistry, Organic
Zhangqiang Yan, Zhen Zhang, Tao Wen, Lihua Ye, Bo Jin, Chihong Zhang, Wenkun Wang, Zhong-Ning Chen, Hu Cai
Summary: Direct alpha-C(sp(3))-H alkylation of hydroaminoalkylation (HAA) catalyzed by (BuOK)-Bu-t/DMSO/O-2 from alpha-aryl benzylamines with styrenes was reported. The reaction provided selectively substituted amines and N-heterocycles under mild conditions. Mechanism studies revealed that alpha-aminoalkyl radicals acted as intermediates and hydrogen atom transfer (HAT) played a crucial role in the (BuOK)-Bu-t/DMSO/O-2 system.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Marek Cubicak, John Bigeon, Pavel Galar, Lukas Ondic, Tomas Tobrman
Summary: A new methodology was developed for preparing cyclic tetrasubstituted alkenes with pi-conjugated substituents, involving regioselective cross-coupling reactions. The prepared alkenes with two pyrene moieties were characterized by absorption and photoluminescence spectra.
Review
Chemistry, Organic
Manfred Braun
Summary: Palladium catalysis enables efficient and versatile domino reactions initiated by intramolecular Mizoroki-Heck reaction and terminated by Suzuki-Miyaura coupling. The cascade reaction is concerned with the stereochemistry of carbon-carbon double bond formation, diastereoselective and enantioselective formation of stereogenic carbon centers. Valuable protocols allow stereo control in the formation of tri- and tetra-substituted double bonds, and the diastereoselective versions enable the formation of multiple stereocenters in mono- and polycycles. The recent development of enantioselective protocols makes the newly formed stereocenters useful and versatile in synthesis.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Review
Chemistry, Applied
Xi Sun, Xu Dong, Hui Liu, Yuying Liu
Summary: Great improvements have been made in palladium-catalyzed radical reactions in recent years, offering more effective strategies for constructing complex heterocyclic compounds and applications in drug discovery. Reactions mediated by Pd(0)/(II)/(IV) typically undergo two-electron transfer processes, while those involving Pd(I) and Pd(III) usually occur via single electron transfer processes. Numerous methodologies involving palladium radical have emerged in the past five years since the publication of the review.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Multidisciplinary
Sichan Dong, Xinjun Luan
Summary: The Catellani reaction, discovered by Catellani in 1997 and further developed by Catellani, Lautens, and others, is a powerful strategy for the synthesis of polysubstituted arenes. This method allows for the simultaneous functionalization of both ortho- and ipso-positions of aryl halides with different electrophiles and terminating agents under the cooperative catalysis of palladium and norbornene. The review focuses on the significant progress in such transformations and categorizes typical Catellani reactions into five parts based on the functionalization modes of ortho-C-H bonds: alkylation, arylation, amination, acylation, or thiolation.
CHINESE JOURNAL OF CHEMISTRY
(2021)
Article
Chemistry, Organic
Xiaoqin Ning, Yongke Chen, Fangdong Hu, Ying Xia
Summary: This study presents the palladium-catalyzed cross-coupling reactions of cyclobutanone-derived N-sulfonylhydrazones with aryl or benzyl halides, demonstrating that the metal carbene process and beta-hydride elimination can occur smoothly in strained ring systems to yield structurally diverse products. The preliminary success in asymmetric carbene coupling reactions in strained ring systems offers a promising route for the synthesis of enantioenriched four-membered-ring molecules.
Article
Chemistry, Multidisciplinary
Marti Garcon, Nicolette Wee Mun, Andrew J. P. White, Mark R. Crimmin
Summary: This study demonstrates a new method of transforming C-H bonds into C-Zn bonds using a palladium catalyst and zinc hydride reagent, which has been successfully applied to various types of arenes with high selectivity. Mechanistic studies show that heterometallic complexes play a crucial role in the catalytic process.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Multidisciplinary
Manoj Kumar Yadav, Sushobhan Chowdhury
Summary: In order to meet the growing demand for synthetic molecules or materials, the field of organic synthesis needs to be more efficient in producing molecules in a shorter time. This can be achieved through green chemical synthesis, which involves reducing the use of solvents, catalysts, reagents, time, effort, and waste. Integrated organic synthesis, particularly through electrochemical cascade reactions, is a strategic tool for fulfilling demand while maintaining green parameters.
Article
Chemistry, Multidisciplinary
Jingjie Yang, Zhuofan Gui, Yuli He, Shaolin Zhu
Summary: An attractive approach for selective functionalization of remote C-H bonds is the metal/hydride shift/cross-coupling reaction sequence. In this study, an unprecedented aryl-to-vinyl 1,4-nickel/hydride shift reaction is reported, which selectively traps migratory alkenylnickel species generated in situ by various coupling partners to access trisubstituted alkenes with excellent regio- and stereoselectivity. Unlike previously reported ipso-aryl coupling reactions, this strategy provides remote alkenyl C-H functionalized products with high yield and excellent chemo-, regio-, and E/Z-selectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Maorui Wang, Chengqian Zhang, Chenggang Ci, Huanfeng Jiang, Pierre. H. Dixneuf, Min Zhang
Summary: Despite the challenges, we have successfully developed a room temperature approach for the direct construction of alpha-hydroxyalkyl cyclic amines through the strategy of electroreductive alpha-hydroxyalkylation. This method offers a broad substrate scope, simplicity in operation, high chemoselectivity, and does not require pressurized H2 gas or transition metal catalysts. The activation of reactants by the zinc ion generated from anode oxidation plays a crucial role in this transformation. This strategy, combined with substrate activation by Lewis acids, is expected to lead to the development of more useful transformations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Applied
Jinyuan Jiang, Jidan Liu, Zhenke Yang, Liyao Zheng, Zhao-Qing Liu
Summary: A one-pot three-component synthesis of benzofuran-3(2H)-ones with tetrasubstituted carbon stereocenters has been successfully developed via Rh(III)-catalyzed C-H/C-C bond activation and cascade annulation, using salicylaldehydes, cyclopropanols, and alkyl alcohols as starting materials.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
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, Multidisciplinary
Rachel J. Baker, Justin Ching, Teh Ren Hou, Ivan Franzoni, Mark Lautens
Summary: The dearomatization of 2-naphthols is a simple method for constructing complex 3D structures from simple planar starting materials using rhodium and acid catalysis under mild conditions. The vinyl cyclopropane molecules formed in this reaction exhibit high chemoselectivity and scalability, and can be further functionalized at different sites. Both computational and experimental evidence were used to understand the reaction mechanism.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
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, Organic
Jonathan Bajohr, Matthias D. Boehme, Jiacheng Gao, F. Ekkehardt Hahn, Mark Lautens
Summary: The diastereoselective synthesis of sulfonylated indolines has been reported. Reactive benzylic sulfinates are generated through a palladium-catalyzed dearomative sulfination of (aza)indole-tethered aryl iodides. These intermediates react with electrophiles in a one-pot, two-step process to give sulfonylated products with good yields and excellent diastereoselectivity. This scalable three-component sequence can also be used for the synthesis of sulfonamides. Furthermore, further derivatizations of aryl iodide containing products lead to the formation of spiro- and alkynylated indoline products.
Article
Chemistry, Physical
Xavier Abel-Snape, Gina Wycich, Mark Lautens
Summary: A palladium-catalyzed three-component domino reaction for accessing indene derivatives is described. The reaction involves the sequential formation of three bonds, with the first two resulting from inter- and intramolecular carbopalladation, and the final bond arising from an attack by a terminating nucleophilic reagent. The starting tether on the iodoarene can be modified to yield either indenes or benzofulvenes. Additionally, the use of an oxabicycle as an acetylene surrogate is demonstrated, and the enantioselective synthesis of indenes is preliminarily explored.
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.
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.
