Article
Chemistry, Organic
Luis R. Domingo, Mar Rios-Gutierrez, Nivedita Acharjee
Summary: The BF3 Lewis acid catalyzed [3+2] cycloaddition reaction was studied using molecular electron density theory, and it was found that BF3 acts as a catalyst, increasing the polarity of the reaction and decreasing the activation enthalpy.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Crystallography
Saeed Alshahrani, Abdullah Mohammed Al-Majid, Abdullah Saleh Alamary, Mar Rios-Gutierrez, Assem Barakat
Summary: A new ethylene derivative was synthesized as a precursor, leading to the formation of a novel spirooxindole embodied with benzimidazole and a pyridine spacer through a [3+2] cycloaddition reaction. The chalcone derivatives 3a-j were obtained by condensation of the acetyl derivative with aryl aldehydes. The reaction of the ethylene derivative, 5-Cl-isatin, and octahydroindole-2-carboxylic acid in a one-pot multi-component fashion enabled the construction of a highly functionalized quaternary center spirooxindole scaffold with a high chemical yield.
Article
Chemistry, Physical
Karolina Zawadzinska, Zuzanna Gadocha, Kamila Pabian, Aneta Wroblewska, Ewelina Wielgus, Radomir Jasinski
Summary: In this study, the first examples of [3+2] cycloaddition reactions between 3,3,3-tribromo-1-nitroprop-1-ene and diarylnitrones were explored, leading to the formation of 3,4-cis-4,5-trans-4-nitroisoxazolidines with full regio- and stereoselectivity. The regioselectivity and molecular mechanism of these processes were analyzed using advanced DFT computational study.
Article
Biochemistry & Molecular Biology
Jowita Kras, Przemyslaw Wolinski, Roman Nagatsky, Oleg M. M. Demchuk, Radomir Jasinski
Summary: In this study, the [3+2] cycloaddition reactions involving Z-C-(3-pyridyl)-N-methylnitrone and series of E-2-R-nitroethenes were investigated both experimentally and theoretically using Molecular Electron Density Theory. The results demonstrate that these reactions proceed under mild conditions and exhibit complete regio- and stereocontrol. Additionally, the ELF analysis reveals a two-stage, one-step mechanism for the studied reaction.
Article
Biochemistry & Molecular Biology
Sabir A. Mohammed Salih, Huda A. Basheer, Jesus Vicente de Julian-Ortiz, Haydar A. Mohammad-Salim
Summary: This study investigated the [3+2] cycloaddition reactions of N-methyl-C-4-methyl phenyl-nitrone 1 and 2-propynamide 2 using molecular electron density theory. The reactions produced four different products through irreversible pathways. The formation of cycloadduct 6 had a slightly increased polar character, observed through global electron density transfer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Applied
Rayhane Hammami, Pascale Maldivi, Christian Philouze, Sebastien Carret, Benjamin Darses, Soufiane Touil, Jean-Francois Poisson
Summary: A variety of 4-phosphinylpyrrolidin-3-ones were synthesized via a [3+2] cycloaddition reaction between aryl aldonitrones and phosphinylallenes. The products were obtained as unique 4,5-trans diastereomers in yields ranging from 47% to 80% for 23 examples. Chiral racemic allenes exhibited a moderate 2:1 to 4:1 2,5-diastereoselectivity. Under the reaction conditions, the cycloadducts undergo a rearrangement to selectively afford the corresponding pyrrolidin-3-ones. DFT calculations provided insights into the mechanism involving the homolytic cleavage of the N-O bond of the cycloadduct.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Green & Sustainable Science & Technology
Przemystaw Wolinski, Agnieszka Kacka-Zych, Barbara Mirostaw, Ewelina Wielgus, Aleksandra Olszewska, Radomir Jasinski
Summary: In this study, a new green procedure for the synthesis of a series of 1,2-oxazine N oxide moieties via Hetero Diels-Alder (HDA) reaction was described, using (2E)-3-aryl-2-nitroprop-2-enenitriles. Unlike most known HDA reactions, this process does not require a Lewis acid-type catalyst, operates under mild conditions, and exhibits full atomic economy and selectivity. Additionally, the reaction process was characterized using Molecular Electron Density Theory (MEDT).
JOURNAL OF CLEANER PRODUCTION
(2022)
Article
Biochemistry & Molecular Biology
Katarzyna Mitka, Katarzyna Fela, Aleksandra Olszewska, Radomir Jasinski
Summary: The molecular mechanism of the [3 + 2] cycloaddition reaction between C-arylnitrones and perfluoro 2-methylpent-2-ene proceeds via a one-step mechanism regardless of the polar nature of intermolecular interactions or the presence of fluorine atoms near the reaction centers. All attempts to locate zwitterionic intermediates on the reaction paths were unsuccessful, and similar results were obtained regardless of the level of theory applied.
Article
Chemistry, Multidisciplinary
Niklas Radhoff, Constantin G. G. Daniliuc, Armido Studer
Summary: The design, synthesis, and application of benzene bioisosteres have been a subject of great interest in the past two decades. Recently, bicyclo[2.1.1]hexanes have been established as highly attractive bioisosteres for ortho- and meta-substituted benzenes. In this study, we present a mild, scalable, and transition-metal-free method for constructing highly substituted bicyclo[2.1.1]hexan-2-ones through Lewis acid-catalyzed (3+2)-cycloaddition of bicyclo[1.1.0]-butane ketones with disubstituted ketenes. The reaction exhibits high functional group tolerance, as evidenced by the successful synthesis of various 3-alkyl-3-aryl and 3,3-bisalkyl bicyclo[2.1.1]hexan-2-ones (26 examples, up to 89% yield). Additionally, postfunctionalization of the exocyclic ketone moiety is demonstrated.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Ewa Dresler, Aneta Wroblewska, Radomir Jasinski
Summary: In this study, the regiochemical aspects and molecular mechanism of the [3 + 2] cycloaddition reaction between nitrous oxide and conjugated nitroalkenes were analyzed through computational calculations. It was discovered that the reaction proceeds via a polar, single-step mechanism regardless of the nature of the nitroalkene, and attempts to locate hypothetical zwitterionic intermediates were unsuccessful. The DFT computational study further revealed that the kinetic preference is the formation of corresponding Delta(2)-4-nitro-4-R-1-5-R-2-1-oxa-2,3-diazolines.
Article
Chemistry, Multidisciplinary
Barsali Banerjee, Nivedita Acharjee, Debnath Palit
Summary: The intramolecular [3 + 2] cycloaddition reactions of allenic nitrones were studied using molecular electron density theory (MEDT). These reactions showed high activation free energies in ethanol, indicating a non-polar character and following a one-step mechanism. The presence of different methylene units affected the cyclization selectivity, in agreement with experimental outcomes. Topological analysis revealed non-covalent interactions at the interatomic bonding regions of the transition states.
STRUCTURAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Yao Xu, Hai-Xiang Gao, Chengkai Pan, Yue Shi, Chi Zhang, Genping Huang, Chao Feng
Summary: By using photoredox catalysis, we have achieved the (3+3) dipolar cycloaddition of nitrones with aryl cyclopropanes. This reaction exhibits excellent regio- and stereoselectivity and can be applied to a variety of aryl cyclopropane substrates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Michael P. Doyle, Ming Bao
Summary: This study achieved a highly enantioselective synthesis of substituted pyrrolidines and 1,2-oxazinanes via stereoretentive [3 + 2]/[3 + 3]-cycloaddition of nonracemic donor-acceptor cyclopropanes with imines, triazines, and nitrones. The reactions were conducted under mild conditions and showed good to high yields with broad applicability. Compared to previous approaches using racemic cyclopropane reactants and chiral ligand catalysts, this study utilized enantioenriched donor-acceptor cyclopropanes as reactants with achiral catalysts.
Article
Chemistry, Multidisciplinary
Agnieszka Kacka-Zych, Radomir Jasinski
Summary: A computational study using density functional theory revealed the possibility of synthesizing seven-membered internal nitronates through cycloaddition reactions, and the mechanism was found to be a polar, stepwise reaction involving zwitterionic intermediates. Additionally, the molecular mechanism of the [4 + 3] cycloaddition reaction was deciphered using bonding evolution theory, which showed the formation of two C-O single bonds through depopulation of N-C and C-C bonding regions.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ewa Dresler, Aneta Wroblewska, Radomir Jasinski
Summary: The molecular mechanism of the Diels-Alder reaction depends on the reaction conditions and solvent polarity, with possible pathways including one-step polar mechanisms and stepwise mechanisms involving zwitterionic or heterocyclic intermediates.
Article
Chemistry, Organic
Assem Barakat, Matti Haukka, Saied M. Soliman, Abdullah Mohammed Al-Majid, M. Ali, Mohammad Shahidul Islam, Abdulnasser Mahmoud Karami, Zaheer Ul-Haq, Luis R. Domingo
Summary: A combined experimental and theoretical study was conducted on a newly synthesized compound based on spirooxindole and thiochromene. The study revealed the importance of intermolecular interactions in crystal stability, and predicted the electronic properties and chemical shifts using computational methods. Furthermore, the compound exhibited anti-cancer activity.
POLYCYCLIC AROMATIC COMPOUNDS
(2023)
Article
Chemistry, Multidisciplinary
Luis R. Domingo, Maria Jose Aurell
Summary: The electrophilic aromatic substitution (EAS) nitration reactions of pyridine, pyridine-1-oxide, and the corresponding protonate species with nitronium NO2+ ion were studied using computational simulations. The reactions follow a stepwise polar mechanism and involve the formation of a labile tetrahedral cation intermediate. In strongly acidic conditions, the nitration reaction of pyridine is entirely converted into the corresponding protonated species, leading to nucleophilic deactivation. However, in the nitration reaction of pyridine-1-oxide, the product is influenced by explicit solvation of the oxygen atom, resulting in either ortho or para nitro compounds.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Luis R. R. Domingo, Nivedita Acharjee
Summary: This study investigates the Grignard reagent-promoted [3+2] cycloaddition reaction of mesitonitrile oxide (MNO) with Baylis-Hilman adduct (BHA) using Molecular Electron Density Theory (MEDT). The analysis reveals that MNO is classified as a zwitterionic three-atom-component (TAC) participating in zw-type 32CA reactions. Despite the strong nucleophilic character of MNO, the low electrophilic character of BHA and BHA:Mg(ii) complex results in low polar character of the corresponding 32CA reactions. The study provides a comprehensive understanding of the role of the Grignard reagent in zw-type 32CA reactions and the change in diastereoselectivity induced by the Mg(ii) cation.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Organic
Luis R. Domingo, Maria Jose Aurell, Mar Rios-Gutierrez
Summary: The role of Cr(CO)(3) coordination in the polar Diels-Alder reactions of naphtoquinone has been studied using Molecular Electron Density Theory. It was found that Cr(CO)(3) does not significantly affect the electronic structure of naphtoquinone. While the formation of the NQ:Cr(CO)(3) complex reduces the activation energy by a small amount, the complex does not exhibit effective catalytic activity in the reactions with cyclic dienes.
POLYCYCLIC AROMATIC COMPOUNDS
(2023)
Article
Chemistry, Organic
Mar Rios-Gutierrez, Alejandro Saz Sousa, Luis R. Domingo
Summary: This study extends the reference electrophilicity and nucleophilicity scales to the most common DFT computational methods used in theoretical organic chemistry studies. Excellent linear correlations were obtained with coefficient of determination R-2 values between 0.97 and 1.00. The study establishes new threshold values for 48 DFT computational levels, enabling direct classification and quantification of the electrophilic and nucleophilic character of molecules without relying on the B3LYP/6-31G(d) scales.
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Antoine de Gombert, Andrea Daru, Tonia S. Ahmed, Michael C. Haibach, Rei Li-Matsuura, Cassie Yang, Rodger F. Henry, Silas P. Cook, Shashank Shekhar, Donna G. Blackmond
Summary: Mechanistic studies of Cu-catalyzed C-N coupling have been conducted to investigate the effects of a recently reported pyrrol-ol ligand on the reaction of sterically hindered aryl iodides with sterically hindered anilines. Kinetic, spectroscopic, and computational techniques were used to determine the active catalyst species and the rate-determining step. It was found that oxidative addition precedes amine coordination, which is in contrast to most known Cu systems. These findings could lead to the development of a general approach for challenging substrates in Cu-catalyzed coupling reactions.
Article
Chemistry, Multidisciplinary
Aziz Moumad, Abderrazzak Bouhaoui, Mohammed Eddahmi, Abderrafia Hafid, Luis R. Domingo, Latifa Bouissane
Summary: The synthesis of N-methyl-5-nitroindazolylacrylonitriles with a series of aldehydes in the presence of piperidine yielded desired products with good to excellent yields. The synthesized compounds were confirmed by H-1, C-13 NMR and mass spectrometry. The reactivity indices of the targeted molecules were studied through DFT/B3LYP/6-311G(d,p) calculations, and the calculated spectroscopy chemical shifts were compared to experimental data. The compounds exhibited significant three-dimensional p-electronic delocalization, which is crucial for understanding their nonlinear optical responses.
Article
Chemistry, Multidisciplinary
Daria Kurandina, Banruo Huang, Wentao Xu, Nikita Hanikel, Andrea Daru, Gautam D. Stroscio, Kaiyu Wang, Laura Gagliardi, F. Dean Toste, Omar M. Yaghi
Summary: In this study, a nitrone-linked covalent organic framework, COF-115, was synthesized by polycondensation reaction of N, N', N'', N'''-(ethene-1,1,2,2-tetrayltetrakis(benzene-4,1-diyl))tetrakis(hydroxylamine) and terephthaladehyde. The formation of nitrone functionality was confirmed through spectroscopic analysis. The porous nature of COF-115 was evaluated through sorption experiments and showed potential for water harvesting and CO2 capture applications. Additionally, the photoinduced rearrangement of COF-115 to an associated amide-linked material was successfully demonstrated.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Mohammad Shahidul Islam, Abdullah Mohammed Al-Majid, Matti Haukka, Zahida Parveen, Nabeela Ravaiz, Abdul Wadood, Ashfaq Ur Rehman, Mar Rios-Gutierrez, Luis R. Domingo, Assem Barakat
Summary: A novel spirooxindole-pyrrolidine compound was synthesized through a one-step process using [3+2] cycloaddition reactions. The compound showed high efficacy as an alpha-amylase inhibitor and could potentially be used for drug discovery in treating type 2 diabetes mellitus (T2DM). The reaction mechanism and interaction with the receptor were studied using molecular electron density theory and molecular docking, respectively, while the physiochemical properties were predicted using in silico ADMET prediction.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Article
Biochemistry & Molecular Biology
Saeed Alshahrani, Abdullah Mohammed Al-Majid, Abdullah Saleh Alamary, Mohamed Ali, Mezna Saleh Altowyan, Mar Rios-Gutierrez, Sammer Yousuf, Assem Barakat
Summary: In this study, a series of spirooxindoles based on benzimidazole, triazole, and isatin moieties were synthesized via a one-step [3+2] cycloaddition reaction. The X-ray crystal structure of the intermediate triazole-benzimidazole was solved for the first time. The low reaction rates and total selectivities were explained by the highly nucleophilic character of azomethine ylide and the strong electrophilicity of chalcones.
Article
Biochemistry & Molecular Biology
Luis R. Domingo, Maria Jose Aurell, Mar Rios-Gutierrez
Summary: The reaction between N-phenyl iminoborane and benzaldehyde, presented by Liu et al., was investigated using Molecular Electron Density Theory (MEDT). The formation of a fused aromatic compound involves three consecutive reactions: the formation of a weak molecular complex between the reactants, an intramolecular electrophilic attack of the activated carbonyl carbon, and a formal 1,3-hydrogen shift. This domino reaction shows similarities to the Bronsted acid catalyzed Povarov reaction.
Article
Crystallography
Saeed Alshahrani, Abdullah Mohammed Al-Majid, Abdullah Saleh Alamary, Mar Rios-Gutierrez, Assem Barakat
Summary: A new ethylene derivative was synthesized as a precursor, leading to the formation of a novel spirooxindole embodied with benzimidazole and a pyridine spacer through a [3+2] cycloaddition reaction. The chalcone derivatives 3a-j were obtained by condensation of the acetyl derivative with aryl aldehydes. The reaction of the ethylene derivative, 5-Cl-isatin, and octahydroindole-2-carboxylic acid in a one-pot multi-component fashion enabled the construction of a highly functionalized quaternary center spirooxindole scaffold with a high chemical yield.
Article
Chemistry, Physical
Mar Rios-Gutierrez, Fabio Falcioni, Luis R. Domingo, Paul L. A. Popelier
Summary: A combined study of Bonding Evolution Theory (BET) and Interacting Quantum Atoms-Relative Energy Gradient (IQA-REG) was conducted on a non-polar zw-type [3+2] cycloaddition (32CA) reaction, aiming to determine the origin of its high activation energy. BET characterizes molecular mechanisms using Catastrophe Theory and the topology of the Electron Localization Function (ELF), while IQA-REG is a quantum topological energy partitioning method. The study showed that the rupture of the nitrone C=N double bond is mainly responsible for the barrier according to BET, while IQA-REG indicates that it is related to the rupture of the ethylene C=C double bond. The complementary use of IQA-REG with BET allows for a more detailed description of molecular mechanisms.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Organic
Luis R. Domingo, Mar Rios-Gutierrez, Patricia Perez
Summary: In this study, the [3 + 2] cycloaddition reactions of phenyl azide with different electronically activated ethylenes were investigated. The reactivity of phenyl azide as both an electrophile and a nucleophile was characterized. The reactions were classified into four groups based on the relative reaction rate constants and electrophilicity and nucleophilicity indices of the ethylenes. The results contradict the existing parabolic correlation model.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Faiza Diaba, Gisela Trenchs
Summary: The first violet light-mediated synthesis of gamma- and delta-lactams from N-alkenyl trichloroacetamides is reported in this paper. The reactions are conducted in tetrahydrofuran or 2-methyltetrahydrofuran as the sole solvent without catalysts or additives, under non-anhydrous conditions in an air atmosphere where the solvent serves as the radical initiator.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Feroze Hussain, Sajjad Ahmed, Ashiq Hussain Padder, Qazi Naveed Ahmed
Summary: This study reports a novel and efficient one-pot synthesis method for mixed phosphorotrithioates, which does not require supplementary additives and shows broad applicability.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Hyunjin Oh, Ikyon Kim
Summary: A new 1,2,4-triazole-pyrrolo[1,2-a]pyrazine hybrid system, 6-acylpyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, was synthesized using a catalyst-free method. This method involved sequential exposure of pyrrole-2-carbonitrile-derived substrates to DMF-DMA and acyl hydrazide, resulting in the formation of acylated pyrazine and 1,2,4-triazole rings, enabling the installation of various substituents at specific positions on the core skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Ming Yan, Si-fan Wang, Yong-po Zhang, Jin-zhong Zhao, Zhuo Tang, Guang-xun Li
Summary: Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. The reaction allows for the gram-scale preparation of sulfinamides and the one-pot synthesis of various sulfonyl amides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Farzaneh Bandehali-Naeini, Zahra Tanbakouchian, Noushin Farajinia-Lehi, Nicolas Mayer, Morteza Shiri, Martin Breugst
Summary: Two tandem catalytic systems were developed for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts. Different maleimide structures can be synthesized using either Pd or Cu catalysis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Tanya Raghava, Anjan Chattopadhyay, Subhadeep Banerjee, Nivedita Sarkar
Summary: Amine substitution of two ortho fluorine atoms of tetrafluoroterephthalonitrile through SNAr chemistry is easily achievable. But further fluorine substitution is only possible under forcing conditions, yielding valuable fluorophores for bioimaging.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Review
Chemistry, Organic
Anju Chadha, Santosh Kumar Padhi, Selvaraj Stella, Sowmyalakshmi Venkataraman, Thangavelu Saravanan
Summary: Alcohol dehydrogenases are enzymes that use cofactors for oxidation or reduction reactions of alcohols or carbonyl compounds. They are utilized in green chemistry and have applications in the production of pharmaceuticals. Recombinant enzymes have solved the challenge of producing purified enzymes in large quantities. Engineered alcohol dehydrogenases have been used in asymmetric synthesis in industry. Various methods have been established for regenerating expensive cofactors to make the enzymatic process more efficient and economically viable.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
