Review
Chemistry, Applied
Daniel Gavina, Marcos Escolano, Javier Torres, Gloria Alzuet-Pina, Maria Sanchez-Rosello, Carlos del Pozo
Summary: Substituted and annulated pyrroles containing chiral centers can be accessed through organocatalytic enantioselective Friedel-Crafts alkylation (FCA) reaction. These compounds are interesting due to their natural occurrence and diverse biological activities. In the past two decades, significant synthetic efforts have been made to develop asymmetric transformations involving pyrroles in the FCA reaction.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Ilya P. Filippov, Mikhail S. Novikov, Alexander F. Khlebnikov, Nikolai V. Rostovskii
Summary: A novel strategy for the synthesis of 1-pyrrolines based on the formal [4 + 1] annulation reaction has been developed in this study. The one-pot approach includes the Rh(II)-catalyzed formation of 4-alkyl-2-azabuta-1,3-dienes, followed by the DBU-promoted cyclization. This method shows good substrate tolerance and can be used to synthesize 1-pyrrolines containing an ester group at the C3 position.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Igor Yu Grishin, Nikolai A. Arutiunov, Dmitrii A. Aksenov, Nicolai A. Aksenov, Alexander Aksenov, Amina Z. Gasanova, Elena A. Sorokina, Carolyn Lower, Michael Rubin
Summary: In this study, polyphosphoric acid was used as a catalyst to efficiently synthesize 3-(1H-indol-3-yl)benzofuran-2(3H)-ones via condensation reaction between 3-(2-nitrovinyl)-1H-indoles and phenols.
Article
Chemistry, Multidisciplinary
Barbara Klausfelder, Patricia Blach, Niels de Jonge, Rhett Kempe
Summary: This study reports a method for the synthesis of 3,4-dihydro-2H-pyrroles via the hydrogenation and cyclization of nitro ketones. The use of inexpensive and readily available starting materials allows for the flexible introduction of various substitution patterns. The reaction shows a broad scope and 23 out of the 33 synthesized compounds are previously unreported.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Organic
Gao-feng Yang, Guang-xun Li, Jin Huang, Ding-qiang Fu, Xiao-kang Nie, Xin Cui, Jin-zhong Zhao, Zhuo Tang
Summary: An unexpected tandem cyclization/transfer hydrogenation reaction was developed for the synthesis of chiral 2,3-disubstituted 1,5-benzodiazepines. The reaction, catalyzed by chiral phosphoric acid, exhibited moderate yields, good selectivities, and high enantiomeric ratios, providing a new method for the synthesis of this class of compounds.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Nikolay Shcherbakov, Gleb D. Titov, Elena Chikunova, Ilya P. Filippov, Nikolai Rostovskii, Vadim Yu Kukushkin, Alexey Yu Dubovtsev
Summary: The developed modular approach to hard-to-reach non-aromatic 3H- and 2H-pyrroles is based on the integration of 2H-azirines and ynamides. The gold-catalyzed [3 + 2] cycloaddition of 2,2-disubstituted 2H-azirines and ynamides provides a high-yielding route to 5-amino-3H-pyrroles. Furthermore, the acid-promoted 1,5-shift-based isomerization of the obtained 5-amino-3H-pyrroles results in fully substituted 5-amino-2H-pyrroles, while the use of 2-substituted 2H-azirine-2-carboxylic acid leads to an aromatic 2-amino-1H-pyrrole scaffold.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Review
Chemistry, Organic
Caroline Dorsch, Christoph Schneider
Summary: This review summarizes recent developments in the area of enantioselective cycloadditions catalyzed by Bronsted acids. Through a straightforward transformation, complex polycyclic heterocyclic compounds can be obtained with high yields and excellent stereocontrol. The enantioselectivity of the reaction is controlled by chiral Bronsted acids.
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Organic
Zeng Gao, Jinlong Qian, Huameng Yang, Jinlong Zhang, Gaoxi Jiang
Summary: Two approaches involving intramolecular and intermolecular cyclization were developed for the construction of a series of benzo[f]pyrrolo[1,2-a][1,4]azepines using Bronsted acid catalysts. The intramolecular dehydroxylation/ring closure reaction and intermolecular addition reaction both provided high yields of the desired compounds.
Article
Chemistry, Medicinal
Kiran S. Toti, Rajkumar Verma, Michael J. McGonnigle, Daylin Gamiotea Turro, Zhiwei Wen, Sarah A. Lewicki, Bruce T. Liang, Kenneth A. Jacobson
Summary: This study reveals the potential of P2X4 receptor antagonists in treating ischemic stroke and demonstrates neuroprotective and memory-enhancing activities in an animal model. Specific compounds show selectivity and efficacy in vivo, and exhibit the ability to reduce brain atrophy in a mouse stroke model.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Azusa Kondoh, Masahiro Terada
Summary: A new methodology for the synthesis of 2,2-disubstituted 2H-chromenes has been developed by utilizing the [1,2]-phospha-Brook rearrangement and Bronsted base catalysis. This methodology involves the catalytic generation of a carbanion and subsequent highly diastereoselective conjugate addition, resulting in the formation of adducts with an alkenylphosphate moiety.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Applied
Zhengjie Le, Yiwen Zhu, Zhi-Peng Bao, Jun Ying, Xiao-Feng Wu
Summary: A new palladium-catalyzed reaction has been developed for the efficient synthesis of 1,5-dihydro-2H-pyrrol-2-ones using benzene-1,3,5-triyl triformate as the CO source.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Shimin Jiang, Sha Du, Jiang Bai, Xi Chen, Meng Liang, Shihong Lin, Mu-Jia Luo, Xian-Rong Song, Qiang Xiao
Summary: An efficient and practical cascade cyclization of 1,5-diynols with (RO)2P(O)SH as the acid promoter and nucleophile under mild conditions was developed, leading to the synthesis of a variety of highly substituted benzo[b]fluorenyl-containing S-alkyl phosphorothioates in moderate to excellent yields. This protocol demonstrated good functional group tolerance, broad substrate scope, and potential practical applications, with water as the sole byproduct.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ali Akbari, Neda Seyedi, Muhammad Saleh Faryabi
Summary: A mild, efficient, and general method has been developed to synthesize new derivatives of 2-aryl/alkyl-3H-indol-3-ones in moderate to excellent yields.
MOLECULAR DIVERSITY
(2022)
Article
Chemistry, Organic
Ke-Wei Chen, Dan-Dan Wang, Si-Jia Liu, Xue Wang, Yu-Chen Zhang, Yi-Ming Tian, Qiong Wu, Feng Shi
Summary: The study focuses on the catalytic asymmetric dearomative cycloaddition of 3-alkyl-2-vinylindoles using chiral phosphoric acid, resulting in the synthesis of chiral pyrroloindolines with two tetrasubstituted stereogenic centers in good yields and excellent stereoselectivities. This reaction introduces new reactivity to 3-alkyl-2-vinylindoles and presents a potential strategy for discovering anti-cancer drug candidates.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Ajithkumar Arumugam, Pushbaraj Palani, Mageshwari Anandan, Venkatramaiah Nutalapati, Gopal Chandru Senadi
Summary: Highly functionalized quinazolin-4(3H)-ones were synthesized from reactions of N-aryl-2-aminobenzamides with trialkylamines under photocatalytic conditions using eosin Y as a catalyst. The reaction was mild and carried out in aqueous acetonitrile, showing a broad substrate scope. Mechanistic studies revealed the electron-donor nature of the intermediate 2,3-dihydroquinazolin-4(1H)-one (3') in the photocatalytic cycle, leading to the formation of 2,3-disubstituted quinazolin-4(3H)-ones (3). This methodology was also successfully extended to the synthesis of benzo [4,5] imidazole[1,2-c] quinazolines and 3 aa on a large scale, as well as the CNS depressant drugs methaqualone (3 la) and mecloqualone (3 pa).
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Hiromasa Yoshioka, Tatsuro Kawamura, Makoto Muroi, Yasumitsu Kondoh, Kaori Honda, Makoto Kawatani, Harumi Aono, Herbert Waldmann, Nobumoto Watanabe, Hiroyuki Osada
Summary: The compound NPD4928 was identified to enhance the sensitivity of various cancer cells to GPX4 inhibitors, potentially having therapeutic potential via the induction of ferroptosis.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Sebastian Peil, Alejandro Gutierrez Gonzalez, Markus Leutzsch, Alois Fuerstner
Summary: This study demonstrates the highly unorthodox hydrogenation transformation of an internal alkyne using [Cp*RuCl](4) as a precatalyst. The reaction shows regioselectivity and forms vinyl carbene complexes with various binding modes as intermediates. The access to spirocyclic and bridged ring systems through this reaction is of great significance in medicinal chemistry.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Tobias Biberger, Nils Noethling, Markus Leutzsch, Christopher P. Gordon, Christophe Coperet, Alois Fuerstner
Summary: In the investigation of ruthenium precatalysts used for light-driven alkyne gem-hydrogenation reactions, a thermally robust anionic dinuclear sigma-dihydrogen complex was found. This complex, formed by the reaction of [(IPr)(eta(6)-cymene)RuCl2] with H-2 under UV-irradiation, is a rare example of anionic sigma-complexes lacking any structural attributes to counterbalance the negative charge and prevent metal center insertion into ligated H-2.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Clement Ghiazza, Lucas Wagner, Sergio Fernandez, Markus Leutzsch, Josep Cornella
Summary: Among the tools available to chemists for drug design of bioactive compounds, the bioisosteric replacement of atoms or groups of atoms is the cornerstone of modern strategies. The enzymatic deaminative hydroxylation remains unmatched despite the interest in amino-to-hydroxyl interchange. The study reports a safe and user-friendly procedure using a pyrylium tetrafluoroborate salt to selectively convert aminoheterocycles to hydroxylated analogues. Mechanistic experiments revealed an unusual mechanism for this aromatic substitution.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Xiuxiu Yang, Edward J. Reijerse, Nils Noethling, Daniel J. SantaLucia, Markus Leutzsch, Alexander Schnegg, Josep Cornella
Summary: In this study, we synthesized, isolated, and characterized two cationic organobismuth(II) compounds with N,C,N pincer frameworks, which mimic crucial intermediates in bismuth radical processes. X-ray crystallography revealed a monomeric Bi(II) structure, and SQUID magnetometry combined with NMR and EPR spectroscopy provided evidence for a paramagnetic S = 1/2 state. High-resolution multifrequency EPR at the X-, Q-, and W-band allowed for precise assignment of the full g- and 209Bi A-tensors. Experimental data and DFT calculations showed that both complexes are metal-centered radicals with minimal delocalization onto the ligands.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Rajat Maji, Santanu Ghosh, Oleg Grossmann, Pinglu Zhang, Markus Leutzsch, Nobuya Tsuji, Benjamin List
Summary: In this study, a catalytic asymmetric hydrolactonization using a confined imidodiphosphorimidate (IDPi) Bronsted acid catalyst is reported. The method is simple, scalable, and compatible with a wide variety of substrates. The mechanism and enantioselectivity of this reaction are elucidated through in-depth physicochemical and DFT analyses.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Hui Zhou, Roberta Properzi, Markus Leutzsch, Paola Belanzoni, Giovanni Bistoni, Nobuya Tsuji, Jung Tae Han, Chendan Zhu, Benjamin List
Summary: Chiral organosilanes are not naturally occurring and are therefore rare. However, a new synthetic approach using racemic silanes as starting materials has been developed, which expands the range of accessible Si-stereogenic compounds. This approach involves the use of strong and confined imidodiphosphorimidate (IDPi) catalysts to enable the dynamic kinetic asymmetric transformation (DYKAT) of racemic allyl silanes, leading to the formation of Si-stereogenic silyl ethers. The products can be easily converted into enantiopure monohydrosilanes. A proposed mechanism involves the epimerization of a catalyst-bound intermediate.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Joyce A. A. Grimm, Hui Zhou, Roberta Properzi, Markus Leutzsch, Giovanni Bistoni, Johanna Nienhaus, Benjamin List
Summary: The discovery of a highly efficient and selective catalyst enables the conversion of natural or synthetic neral to (1R,6S)-trans-isopiperitenol, providing sustainable routes to menthol and cannabinoids.
Article
Multidisciplinary Sciences
Yue Pang, Nils Noethling, Markus Leutzsch, Liqun Kang, Eckhard Bill, Maurice van Gastel, Edward Reijerse, Richard Goddard, Lucas Wagner, Daniel SantaLucia, Serena DeBeer, Frank Neese, Josep Cornella
Summary: In this work, the synthesis and characterization of a monocoordinate bismuthinidene compound with a rigid and bulky ligand were reported. Despite showing diamagnetic properties in all magnetic measurements, multiconfigurational quantum chemical calculations revealed that the compound's ground state is dominated by a spin triplet. The apparent diamagnetism is explained by an extremely large spin-orbit coupling-induced positive zero-field splitting.
Article
Chemistry, Multidisciplinary
Hye Won Moon, Feng Wang, Kalishankar Bhattacharyya, Oriol Planas, Markus Leutzsch, Nils Noethling, Alexander A. Auer, Josep Cornella
Summary: This research investigates the transfer hydrogenation of azoarenes catalyzed by bismuth through experimental and computational studies. The role of protic and hydridic hydrogens in the reaction is identified through kinetic analysis and reactivity studies using p-trifluoromethylphenol and pinacolborane. The possibility of bismuth-ligand cooperativity is also assessed.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Davide Spinnato, Markus Leutzsch, Feng Wang, Josep Cornella
Summary: In this article, a method to transform isoxazoles and oxadiazoles into pyrazoles and 1,2,4-triazoles in one step using a copper catalyst is provided. The method allows for rapid evaluation of different five-membered azole scaffolds, avoiding de novo synthesis of the molecule of interest.
Article
Chemistry, Organic
Sarah Zinken, Axel Pahl, Michael Grigalunas, Herbert Waldmann
Summary: Chromaline pseudo-natural products are a collection of topologically diverse compounds that were designed to access novel biological space by combining chromane and 4H-quinoline natural product fragments. The compounds possess both drug-like and natural product-like properties and have distinct bioactivity profiles compared to previous pseudo-natural product collections. This suggests that the new fragment combination may have led to a unique bioactivity.
Article
Chemistry, Multidisciplinary
Takuya Tsuruta, Davide Spinnato, Hye Won Moon, Markus Leutzsch, Josep Cornella
Summary: We present a dual-catalyzed C-H trifluoromethylation of (hetero)-arenes using CF3SO2Cl under light irradiation. The reaction enables direct modification of various heterocycles with different functional groups. Structural and computational studies reveal that the reaction proceeds through an open-shell redox reaction at bismuth, involving three unusual elementary steps.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Chemistry, Multidisciplinary
Caitlin Davies, Saad Shaaban, Herbert Waldmann
Summary: The development of metal complexes containing chiral cyclopentadienyl (Cpx) ligands has been widely used in asymmetric catalysis, including challenging C-H bond functionalizations. These chiral Cpx ligands are often associated with Group 9 metals, early transition metals, and rare-earth elements, allowing the access to privileged scaffolds with high stereocontrol, commonly found in bioactive compounds.
TRENDS IN CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Daniel J. Foley, Herbert Waldmann
Summary: Natural product-inspired compound collections are important sources for discovering new bioactive compounds for treating diseases. Ketones, with their variety of synthetic transformations, prevalence as commercial building blocks, and relative ease of synthesis, can be valuable as starting materials for the synthesis of natural product-inspired compounds. This review explores the use of ketones as general precursors and summarizes the synthetic transformations available for the annulation of natural product ring-systems to ketone starting materials.
CHEMICAL SOCIETY REVIEWS
(2022)
