Article
Chemistry, Organic
Tao Liu, Tuanli Yao, Ruihua Guo, Xiangyang Qin
Summary: A palladium-catalyzed cascade reaction was developed for the synthesis of tetrahydro-beta-carbolines and other polycyclic indoles from 2-(hydroxyenyl)sulfonanilides by combining Pd(ii)-catalyzed cyclization of alkynes and intramolecular redox-relay Heck arylation of alkenols. This method allows the construction of two rings and installation of a remote carbonyl group in a single operation, offering broad synthetic utility for further elaborations.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Tsukasa Hirokane, Touya Kariya, Misa Takata, Kenji Matsumoto, Masahiro Yoshida
Summary: The reaction between 2-alkynylazetidines and alcohols with a gold catalyst is reported, leading to the synthesis of various substituted delta-amino-alpha,beta-unsaturated ketones through gold-promoted nucleophilic attack of alcohols followed by ring-opening of azetidine ring.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Yiding Wang, Lei Shen, Helin Wang, Yixin Luo, Qingle Zeng
Summary: The ring-opening addition reaction of activated vinyl cyclopropanes with N-tosylhydrazones in the presence of palladium(0) and triphenylphosphine yields N-tosylhydrazone butenylmalonate compounds. Aromatic aldehyde-derived N-tosylhydrazones produce both terminal and internal N-allylated products, with the terminal products being the major ones. On the other hand, ketone-derived tosylhydrazones only yield terminal addition products. The transformation relationship between the terminal and internal N-allylated products is also observed. A reasonable mechanism based on preliminary experimental results is proposed.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Xu-Heng Yang, Jian Huang, Fang Wang, Zhuoliang Liu, Yujiao Li, Cheng-an Tao, Jianfang Wang
Summary: A synthetic strategy based on sequential application of aza-Claisen rearrangement, C-H functionalization, C-N coupling, and cyclization has been developed for the synthesis of various medium-sized N-heterocycles of pharmaceutical relevance, providing a highly efficient synthesis of N-heterocycles of different ring sizes in moderate to good yields.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Multidisciplinary
Boon Beng Tan, Ming Hu, Shaozhong Ge
Summary: A ligand-controlled cobalt-catalyzed ring-opening dihydroboration method is developed to access versatile skipped diboronates. Various arylidenecyclopropanes reacted with pinacolborane to yield 1,3- or 1,4-diboronate products with high regioselectivity. The resulting diboronates can undergo various transformations, enabling selective installation of different functional groups on alkyl chains.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Xiaoyi Fu, Tianyu Zhang, Jingjing Wu, Yijie Sun, Fanhong Wu
Summary: A nickel-catalyzed aminofluoroalkylative cyclization reaction of unactive alkenes with iododifluoromethyl ketones was developed to construct versatile difluoroalkylated nitrogen-containing heterocycles, yielding aziridines, pyrrolidines, and piperidines in moderate to high yields. This method demonstrates a broad substrate scope and has been successfully scaled up to gram scale.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Sara Meninno, Alessandra Lattanzi
Summary: A one-pot multicomponent reaction, involving Knoevenagel reaction, asymmetric epoxidation, and domino ring-opening cyclization, has been developed for the synthesis of 3-aryl/alkyl piperazin-2-ones and morpholin-2-ones. The reaction proceeds in good yields (38-90%) and high enantioselectivity (up to 99% ee), with two out of three steps being catalyzed by a quinine derived urea. The method has also been applied to the enantioselective synthesis of a key intermediate for the antiemetic drug Aprepitant.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Xianjun Xu, Liangliang Song, Huangdi Feng, Erik V. Van Der Eycken
Summary: The development of economically feasible strategies for constructing structurally diverse isoquinolones is still challenging. In this study, a practical Pd-catalyzed cyclization/base-promoted ammatization/ring-opening protocol for N-propargyl-1,3-oxazolidines with carboxylic acids was disclosed. The domino reaction resulted in a series of ester-functionalized isoquinolones in moderate to good yields through C-O bond cleavage, demonstrating a broad functional group tolerance.
MOLECULAR CATALYSIS
(2022)
Article
Chemistry, Organic
Pei-Pei Xu, Jun-Yi Liao, Jia-Jie Zhang, Wei-Min Shi, Cui Liang, Gui-Fa Su, Dong-Liang Mo
Summary: Various N-vinylindoles and N-vinylpyrroles were synthesized in moderate to good yields through nickel(II)-catalyzed [3 + 2] cycloaddition. A rational mechanism for the formation of N-vinylindoles was proposed based on labeled experiments and key intermediates detected by mass spectrometry. The method highlights nickel(II)-controlled cyclization, atom-economical reaction, broad substrate scope, good functional group tolerance, and high Z-stereoselectivity.
Article
Chemistry, Multidisciplinary
Zhipeng Zheng, Youge Pu, Javier Adrio, Patrick J. Walsh
Summary: This study reports a synthetic method for trans-aziridines using imines and benzylic or alkyl halides with sulfenate anions (PhSO-) as catalysts. The method shows broad applicability and good diastereoselectivity, and can be used with substrates bearing heterocyclic aromatic groups, alkyl, and electron-rich and electron-poor aryl groups. Ring-opening reactions further allow functionalization of aziridines containing cyclopropyl or cyclobutyl groups.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Applied
Patricia Garcia-Martinez, Olaya Bernardo, Javier Borge, Javier Gonzalez, Luis A. Lopez
Summary: The BF3 & sdot;OEt2-catalyzed reaction of azulene with N-protected aziridines provides a general and efficient method for synthesizing phenethylamine-azulene conjugates with high regioselectivity (up to 91% yield). Stereochemical studies and DFT calculations confirm a concerted SN2-type mechanism for the ring-opening reaction of aziridine.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Chiara Volpe, Sara Meninno, Carlo Crescenzi, Michele Mancinelli, Andrea Mazzanti, Alessandra Lattanzi
Summary: This study demonstrates an enantioselective one-pot catalytic strategy for the synthesis of dihydroquinoxalinones, using a combination of catalysts and intermediates to achieve high enantioselectivity in the formation of medicinally relevant heterocycles. The reusability of the organocatalyst and the mechanistic insights into the DROC process provide valuable information for further development of enantioselective synthesis strategies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Inorganic & Nuclear
Francisco Villalba, Ana C. Albeniz
Summary: Hydrazones play a crucial role as ligands in palladium-catalyzed cross coupling reactions, but their interaction with palladium and reaction mechanism remain understudied.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Multidisciplinary
Guofeng Zhao, Yi Wu, Hai-Hong Wu, Junfeng Yang, Junliang Zhang
Summary: This study presents a Pd-catalyzed enantioselective three-component coupling for the synthesis of chiral diarylmethyl alkynes using a novel chiral ligand. The method features readily available starting materials, high enantioselectivity, and ease of operation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Jun-An Xiao, Huan Zhang, Xue-Ling Luo, Ru-Fang Meng, Wei Wang, Wei-dong Lu, Wei Su, Chenxiang Lin, Peng-Ju Xia, Hua Yang
Summary: A palladium-catalyzed ring-opening [3 + 2]-annulation reaction was developed for the synthesis of seven-membered benzosultams from spirovinylcyclopropanyloxindoles and cyclic N-sulfonylimines. The reaction yielded a wide range of compounds with both a quaternary center and axially chiral biaryl scaffolds, with an average yield of 87% and moderate to excellent diastereoselectivities. Enantioenriched benzosultams were also successfully synthesized in good yields with excellent atropoenantioselectivities using the Pd-2(dba)(3)/(S,S,S)-SKP ligand. The practical utility of this method was demonstrated through gram-scale reactions and diversified synthetic transformations.
Article
Chemistry, Multidisciplinary
Pia Mueller, Adam D. Clayton, Jamie Manson, Samuel Riley, Oliver S. May, Norman Govan, Stuart Notman, Steven Ley, Thomas W. Chamberlain, Richard A. Bourne
Summary: The study compared the performance of four different multi-objective optimisation algorithms in chemical reaction optimisation, finding that EIMEGO achieved the highest hypervolume with the lowest number of experiments, while TSEMO performed better in cases with three objectives.
REACTION CHEMISTRY & ENGINEERING
(2022)
Article
Chemistry, Inorganic & Nuclear
Lorenzo Biancalana, Matteo Fiaschi, Stefano Zacchini, Fabio Marchetti
Summary: By reacting the isocyanide complex [Fe2Cp2(CO)(3)(CNMe)], 1(Me), with BrCN in acetonitrile, the unprecedented N-methylcyanamido-(cyano)alkylidene complex [Fe2Cp2(CO)(3){mu-C(CN)N(CN)Me}], 3, can be synthesized. This reaction represents a rare example of C-C bond formation taking place at a metal complex despite the presence of competitive oxidative addition pathways.
INORGANICA CHIMICA ACTA
(2022)
Article
Chemistry, Organic
Oliver M. Griffiths, Steven V. Ley
Summary: The photocatalytic generation of N-centered radicals has been employed for the synthesis of N-heterospirocycles, offering a reliable method for the construction of beta-spirocydic pyrrolidines from N-allylsulfonamides and alkenes. This study demonstrates the successful construction of various beta-spirocyclic pyrrolidines, including drug derivatives, with moderate to very good yields. Derivatization of the products and a viable scale-up procedure using flow chemistry techniques have also been achieved.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Analytical
Sarah A. P. Pereira, Lorenzo Biancalana, Fabio Marchetti, Paul J. Dyson, M. Lucia M. F. S. Saraiva
Summary: In this study, a new miniaturized micro sequential injection coupled with the lab-on-valve technique was used for DHFR inhibitory studies on metal-based anticancer compounds. The system provided IC50 values for the metal complexes, with half falling in the low micro M range. The mu SIA-LOV system is versatile, robust, rapid, and easy to operate, with automated determination of DHFR inhibition.
SENSORS AND ACTUATORS B-CHEMICAL
(2022)
Article
Chemistry, Applied
Giulio Bresciani, Lorenzo Biancalana, Stefano Zacchini, Guido Pampaloni, Gianluca Ciancaleoni, Fabio Marchetti
Summary: The catalytic activity of a series of diiron complexes based on the {Fe2Cp2(CO)(x)} core (x = 2-3) and containing a bridging aminocarbyne ligand was screened in the transfer hydrogenation reaction of cyclohexanone from isopropanol. The best catalyst among these complexes was [Fe2Cp2(CN)(CO)(mu-CO){mu-CN(Me)(4-C6H4OMe)}], 3a, which exhibited moderate activity and showed a carbyne-centered mechanism, stabilized by the cyanide co-ligand, as supported by DFT calculations and IR analyses.
APPLIED ORGANOMETALLIC CHEMISTRY
(2023)
Article
Materials Science, Biomaterials
Melissa Santi, Valentina Frusca, Maria Laura Ermini, Ana Katrina Mapanao, Patrizia Sarogni, Alessandra Gonnelli, Noemi Giannini, Agata Zamborlin, Lorenzo Biancalana, Fabio Marchetti, Valerio Voliani
Summary: Head and neck squamous cell carcinomas (HNSCCs) are a complex group of malignancies that currently rely on platinum-based chemotherapy with severe side effects. Researchers are exploring alternative metal complexes to reduce adverse reactions. The concurrent administration of cisplatin and emerging metal complexes shows promising results in increasing the efficacy of HNSCC treatment while reducing side effects.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Article
Chemistry, Multidisciplinary
Pia Mueller, Aikaterini Vriza, Adam D. Clayton, Oliver S. May, Norman Govan, Stuart Notman, Steven V. Ley, Thomas W. Chamberlain, Richard A. Bourne
Summary: Automated platforms enable fast and efficient optimization of chemical systems with single and multiple objectives. In this study, we demonstrate the application of automated optimization platforms for chemical screening of sulfide oxidations in flow. The identification of unique optima for each substrate emphasizes the importance of rapid and individual experimental optimization for successful compound screening.
REACTION CHEMISTRY & ENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Samuel L. Bourne, Franz Amann, Steven V. Ley
Summary: This article provides an overview of the factors contributing to the rise of flow chemistry in the pharmaceutical industry over the past two decades. It highlights the challenges faced by the industry and how scientific progress has helped to overcome them. Current trends and examples of progress at CARBOGEN AMCIS are discussed, giving a speculative glimpse into the future of drug development and manufacturing.
Article
Chemistry, Inorganic & Nuclear
Lorenzo Bonaldi, Marco Bortoluzzi, Stefano Zacchini, Guido Pampaloni, Fabio Marchetti, Lorenzo Biancalana
Summary: The chemistry of 1,2,4,5-tetrazines has attracted attention in the synthesis and application field. Recent studies have shown that regioselective reactions with alkynes and alkenes are favored when the tetrazine ring is coordinated to certain metal centers. This study explores the reactivity of tetrazines with chalcogenocyanate anions and demonstrates the formation of new heterocycles. The resulting ruthenium complexes were characterized using various analytical and spectroscopic techniques.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Chiara Saviozzi, Sara Stocchetti, Giulio Bresciani, Lorenzo Biancalana, Guido Pampaloni, Fabio Marchetti
Summary: The reactions between diiron aminocarbyne complexes and primary amines resulted in the replacement of the acetonitrile ligand and the formation of new diiron complexes. The diiron-oxazolidinone conjugate was also successfully prepared. However, the reactions with NHEt2 in the presence of Me3NO led to unstable products. The behavior of the diiron complexes in aqueous media was also studied.
Article
Chemistry, Inorganic & Nuclear
Sara Benetti, Maria Dalla Pozza, Lorenzo Biancalana, Stefano Zacchini, Gilles Gasser, Fabio Marchetti
Summary: Novel diiron vinyliminium complexes were synthesized and characterized by various spectroscopic techniques. Their solubility in D2O, Log Pow coefficients, and stability in aqueous media were determined. The antiproliferative activity of these complexes on cancer cell lines was evaluated and their mechanism of action was investigated by assessing their influence on mitochondrial respiration.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Physical
Roberta Colaiezzi, Chiara Saviozzi, Nicola di Nicola, Stefano Zacchini, Guido Pampaloni, Marcello Crucianelli, Fabio Marchetti, Andrea Di Giuseppe, Lorenzo Biancalana
Summary: The reductive N-monomethylation of nitroarenes can be conveniently realized in one-pot using methanol as the reductant, methylating agent, and solvent. New ruthenium(II) arene complexes were developed as efficient catalytic precursors for the tandem reduction/N-methylation of aromatic nitrocompounds with methanol, starting from commercially available and inexpensive dioxime ligands.
CATALYSIS SCIENCE & TECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Beatrice Campanella, Simona Braccini, Giulio Bresciani, Michele De Franco, Valentina Gandin, Federica Chiellini, Alessandro Pratesi, Guido Pampaloni, Lorenzo Biancalana, Fabio Marchetti
Summary: Diiron vinyliminium complexes are promising organometallics with potential anticancer activity. The synthesis and evaluation of [Fe2Cp2(CO)(mu-CO){mu-eta(1):eta(3)-C(R-3)C(R-4)CN(R-1)(R-2)}]CF3SO3 (2a-c, 4a-d) complexes were performed, including their solubility in D2O, Log P-ow, stability in D2O/Me2SO-d(6) mixture, and antiproliferative activity against ovarian cancer cell lines A2780 and A2780cisR, as well as the nontumoral cell line Balb/3T3 clone A31. The cytotoxicity data of 50 vinyliminium complexes were correlated with the structural properties, showing a positive correlation between octanol-water partition coefficient and relative antiproliferative activity on ovarian cancer cell lines. However, the effects of different substituents provided guidelines for the development of novel, more effective compounds. Three additional complexes (4p-r) were designed, synthesized, and biologically investigated, revealing their ability to inhibit thioredoxin reductase enzyme and induce cancer cell production of reactive oxygen species.
Article
Chemistry, Multidisciplinary
Ricardo Labes, Julio C. Pastre, Richard J. Ingham, Claudio Battilocchio, Henrique M. Marcon, Mariana C. F. C. B. Damiao, Duc N. Tran, Steven V. Ley
Summary: This study reports the rapid synthesis of 2-pyrazolines from aldehydes via [3 + 2] cycloaddition of unstabilised diazo species and mono and di-substituted alkenes. The development includes semi-continuous and fully continuous methods, with a fully automated compound library generation and a graphical interface for automation control.
REACTION CHEMISTRY & ENGINEERING
(2023)
Article
Chemistry, Inorganic & Nuclear
Alberto Gobbo, Sarah A. P. Pereira, Lorenzo Biancalana, Stefano Zacchini, M. Lucia M. F. S. Saraiva, Paul J. Dyson, Fabio Marchetti
Summary: Compared with Ru-II-arene compounds, the medicinal potential of homologous Ru-II-tpm compounds [tpm = tris(pyrazolyl)methane] is not well explored. A series of [RuCl(kappa(3)-tpm)(PPh3)(L)]Cl complexes were synthesized by reacting pyridine, 4-pyridinemethanol, and four functionalized pyridines with the precursor [RuCl(kappa(3)-tpm)(PPh3)(2)]Cl. The complexes exhibited antiproliferative activity against cancerous cell lines and inhibition towards COX-2 and GSTP1 enzymes.
DALTON TRANSACTIONS
(2022)
