Review
Chemistry, Applied
Yong-Xing Song, Da-Ming Du
Summary: The aza-Michael addition cascade reaction is an important synthetic method for constructing functionalized C-N bonds, widely used in the synthesis of chiral drugs, intermediates, and natural products. This review highlights recent developments in asymmetric synthesis, including various types of aza-Michael addition triggered cascade reactions, reaction mechanisms, and derivatization experiments.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Multidisciplinary
Maria Sanchez-Rosello, Marcos Escolano, Daniel Gavina, Carlos del Pozo
Summary: The asymmetric intramolecular aza-Michael reaction (IMAMR) is a convenient strategy for generating heterocycles with nitrogen-substituted stereocenters, finding widespread applications in the total synthesis of alkaloids and biologically relevant compounds. Recent developments in asymmetric versions of IMAMR mainly involve the use of organocatalysts, such as chiral imidazolidinones and diaryl prolinol derivatives. The use of N-sulfinyl imines with dual roles has also emerged as a versatile mode for performing the asymmetric IMAMR.
Article
Chemistry, Applied
Fabian Scharinger, Matthias Weil, Michael Schnuerch, Katharina Bica-Schroeder
Summary: We introduce a simple method for the synthesis of chiral diazabicycloalkanes in a single reaction step. This method is applicable to a wide range of enals and has high functional group tolerance.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Review
Chemistry, Applied
Alexander Yu. Rulev
Summary: The 1,4-conjugated addition of nitrogen centered nucleophiles to electron-deficient alkenes is a significant and widely used reaction. Previous protocols mainly focused on strong Michael donors, but recent studies have shown the increasing popularity of weak nitrogen nucleophiles in conjugate addition. The use of more efficient catalyst systems has achieved impressive progress in this area. This review critically analyzes the results obtained in reactions of weak nucleophiles with electron-deficient alkenes over the past twelve years.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Johannes Nebauer, Christian Neiss, Marcel Krug, Alexander Vogel, Dominik Fehn, Shuhei Ozaki, Frank Rominger, Karsten Meyer, Kenji Kamada, Dirk M. Guldi, Andreas Goerling, Milan Kivala
Summary: This article describes a new type of nitrogen-centered polycyclic scaffold synthesized through intramolecular oxidative cyclodehydrogenation of tri(1-naphthyl)amine, which is the first example of a direct 3-fold cyclization of a triarylamine under oxidative conditions. Experimental and theoretical studies reveal the impact of cyclization on the electronic and photophysical properties, and mechanistic studies suggest the cyclization occurs under kinetic control via a dicationic mechanism.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Gurupada Hazra, Sayantan Kundu, Rambabu Dandela, Barla Thirupathi
Summary: A facile synthetic approach for 6H-pyrrolo[3,2,1-de]acridines has been developed by using a cascade N-nucleophilic addition-cyclic Michael addition process. The reaction was conducted under metal-free conditions using arynes and indoles substituted with Michael acceptors. Additionally, photophysical studies showed that the newly synthesized pyrroloacridine compounds exhibited good fluorescence emission properties.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Review
Chemistry, Organic
Pratibha Sharma, Raakhi Gupta, Raj K. Bansal
Summary: The article reviews the literature on asymmetric aza-MR of amines and amides catalyzed by organocatalysts in the past 10 years. Studies show that both types of organocatalysts, whether through non-covalent interactions or through covalent bond formation, play important roles in this reaction.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Polymer Science
Aymeric Genest, Daniel Portinha, Emmanuel Pouget, Khalid Lamnawar, Francois Ganachaud, Etienne Fleury
Summary: Supramolecular zwitterionic silicones were synthesized by aza-Michael reaction between acrylic acid and amine-functional polydimethylsiloxanes. The study showed that the aza-Michael addition proceeded smoothly under mild conditions, resulting in the formation of monoadducts, di-adducts, and residual amine. The assembly of zwitterionic moieties led to an increase in viscosity and phase separation, with the observation of an additional glass transition at -40 degrees C.
MACROMOLECULAR RAPID COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Zoran Glasovac, Luka Baresic, Davor Margetic
Summary: The reaction mechanism of guanidinium chlorides with dimethyl acetylenedicarboxylate in a aza-Michael addition reaction/intramolecular cyclization was investigated using DFT M06-2X and B3LYP computational approaches. The energies of the products were compared with experimental data or product ratios obtained from other methods. The diversity of the products was explained by the formation of different tautomers upon deprotonation. The initial nucleophilic addition was found to be the most energetically demanding step, and the overall reaction was exergonic due to methanol elimination during cyclization.
Article
Chemistry, Multidisciplinary
Mateusz Dyguda, Artur Przydacz, Lukasz Albrecht
Summary: This manuscript describes the application of dearomative formal normal-electron-demand aza-Diels-Alder cycloaddition in the synthesis of tetrahydrofuropyridines. The method involves the aminocatalytic activation of 2-alkyl-3-furfurals and proceeds via the formation of dearomatized dienamine intermediate. The obtained cycloadducts can be further transformed into tetrahydrofuropyridines or functionalized cinnamates. The mechanism of the transformation was confirmed through DFT calculations.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Mateusz Dyguda, Artur Przydacz, Lukasz Albrecht
Summary: This manuscript describes the application of dearomative formal normal-electron-demand aza-Diels-Alder cycloaddition in the synthesis of tetrahydrofuropyridines. The developed approach utilizes aminocatalytic activation of 2-alkyl-3-furfurals that proceeds via formation of the dearomatized dienamine intermediate. The obtained cycloadducts can be further transformed into tetrahydrofuropyridines or functionalized cinnamates.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Subaramaniam Thangamalar, Kannupal Srinivasan
Summary: The ring-opening reaction of nitro-substituted donor-acceptor cyclopropanes with pyrazoles in DMSO was investigated. Unexpectedly, the cyclopropanes underwent Kornblum-type ring-opening oxidation with DMSO to form aroylmethylidene malonates as intermediates in the reactions. The intermediates further underwent aza-Michael addition with pyrazoles in tandem manner to give the corresponding aza-Michael adducts. The highlights of the methodology include the occurrence of ring-opening/oxidation under neutral conditions with DMSO and formation of aza-Michael adducts with pyrazoles under catalyst-free conditions.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Review
Chemistry, Applied
Maxim G. Vinogradov, Olga V. Turova, Sergei G. Zlotin
Summary: This review retrospectively considers the pivotal achievements and recent advances in catalytic asymmetric aza-DAR reported up to 2020, showcasing their potency for enantioselective synthesis of useful chiral piperidine, quinoline, pyridazine, oxazine, and oxadiazine derivatives. The data are systematized based on key electron transfer modes and attainable heterocyclic products, with significant attention to activation strategies and plausible reaction pathways over stereoselective cyclization processes. The review contains 310 references and 122 synthetic schemes.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Physical
Guangtong Hai, Haihui Wang
Summary: Accurate prediction of catalytic performance based on DFT calculation is crucial for nitrogen fixation. However, current computational methods ignore the effects of electrode potential and solvation, resulting in large deviations between predicted and measured potentials. This study proposes an external iteration method and a hybrid solvent model to account for these effects, achieving good agreement between theoretical and experimental potentials. These findings have important implications for prediction of other electrocatalytic systems.
Article
Chemistry, Multidisciplinary
Subhankar Biswas, Siddhartha K. Purkayastha, Ankur K. Guha, Subhas Chandra Pan
Summary: An asymmetric Michael addition/hydroarylation reaction sequence, catalyzed by a squaramide and a combination of silver and gold salts, has been developed to synthesize cyclic aza-spirooxindole derivatives in high yields and enantioselectivities. Computational study was also performed.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Kun Guo, Qian Zeng, Alba Villar-Yanez, Carles Bo, Arjan W. Kleij
Summary: A Ni-catalyzed decarboxylative silylation of alkynyl cyclic carbonates has been reported, which serves as versatile propargylic surrogates and affords a wide range of highly substituted 2,3- and 3,4-allenol products in good yields. The formal cross-coupling between a tentative intermediate Ni(allenyl) and the silyl reagent can be further extended to enantiospecific conversions providing access to chiral allene synthons. This study is of significance as it represents the first Ni-catalyzed propargylic silylation proceeding through an S(N)2' manifold.
Article
Chemistry, Physical
Xuetong Li, Alba Villar-Yanez, Charlene Ngassam Tounzoua, Jordi Benet-Buchholz, Bruno Grignard, Carles Bo, Christophe Detrembleur, Arjan W. Kleij
Summary: We have developed a silver-catalyzed cascade conversion method for the selective formation of keto-functionalized cyclic carbonates using modular alkyne-1,n-diols and carbon dioxide. This method is characterized by its operational simplicity, excellent scope of carbonate-based heterocycles, and mild reaction conditions.
Article
Chemistry, Physical
Anirban Mondal, Niklas O. Thiel, Ruth Dorel, Ben L. Feringa
Summary: The phosphorus stereocentre is crucial in various compounds and efforts are underway to develop stereoselective synthesis methods. Despite advances in metal-catalysed C-P bond formation, generating homochiral phosphorus stereocentres remains challenging. An efficient and flexible method has been presented for the synthesis of various classes of P-chirogenic compounds through functionalization of phosphonamidates with excellent stereoselectivity.
Article
Chemistry, Inorganic & Nuclear
Diego Garay-Ruiz, Cristiano Zonta, Silvia Lovat, Joan Gonzalez-Fabra, Carles Bo, Giulia Licini
Summary: This study reveals the catalytic pathway and influencing factors of sulfide oxidation through experimental and theoretical investigations. The steric effects of sulfides, ligands, and oxidants are crucial for the formation of different intermediates and reaction pathways.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Chang Quo, Alba Villar-Yanez, Diego Garay-Ruiz, Jordi-Benet Buchholz, Caries Bo, Arjan W. Kleij
Summary: Structurally diverse heterobicyclic diethers can be conveniently synthesized using a binary catalyst, which has potential applications in various fields. Mechanistic studies and computational investigations have provided insights into the reaction pathway and the role of the catalyst, laying a foundation for further research.
Article
Chemistry, Organic
Claudia Marques, Faiza Diaba, Enrique Gomez-Bengoa, Josep Bonjoch
Summary: A synthetic approach to functionalized ABC-tricyclic framework of calyciphilline A-type alkaloids is reported, which involves radical cyclization and stereocontrolled aldol cyclization. The resulting compound serves as a building block for this class of alkaloids, and the synthesis of azatricyclic compound I constitutes a formal synthesis of himalensine A.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Luis Bustos, Carlos Echiburu-Chau, Alejandro Castro-Alvarez, Ben Bradshaw, Mario J. Simirgiotis, Marco Mellado, Claudio Parra, Mauricio Cuellar
Summary: This study determined the cytotoxicity of eleven chalcones synthesized from two acetophenones and investigated their possible mechanisms. Two chalcones showed significant inhibitory effects and are potential candidates for further research and development.
Article
Chemistry, Inorganic & Nuclear
Enric Petrus, Mireia Segado-Centellas, Carles Bo
Summary: Understanding the speciation and formation mechanisms of molecular metal-oxo-clusters is important in various fields, and this study successfully predicted the speciation and formation processes of polyoxovanadates, -niobates, and -tantalates using computational methods. The results showed good agreement with experiments and demonstrated the reliability of the method in exploring polyoxometalates' chemistry.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Laura G. Rodriguez, Ana Delgado, Carlos J. Ciudad, Veronique Noe, Josep Bonjoch, Ben Bradshaw
Summary: A two-step reaction was developed to synthesize a ring system found in natural products. The reaction was explored with eight substituted nitrobenzenes, achieving yields of up to 87%. One of the benzazocine compounds, 4h, exhibited high cytotoxicity and was active against eight cancer cell lines.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Ruth Dorel, Alice R. Wong, James J. Crawford
Summary: Non-absorbable small-molecule drugs targeted to the gut provide a safe and non-systemic therapeutic approach. They are confined to the gastrointestinal tract, minimizing exposure to other parts of the body while increasing the local concentration at the site of action. This review discusses the recent advances in gut-restricted therapeutics and the strategies employed by medicinal chemists to develop drugs with minimal intestinal absorption.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Enric Petrus, Diego Garay-Ruiz, Markus Reiher, Carles Bo
Summary: In this study, a unique computational approach was used to successfully simulate the self-assembly processes of metal-oxide nanoclusters. By estimating activation energies and correcting pK (a) values, multi-time-scale kinetic simulations were conducted, reproducing reactions ranging from tens of femtoseconds to months of reaction time. Analysis of the kinetic data and reaction network topology revealed the details of the main reaction mechanisms, explaining the origin of kinetic and thermodynamic control. Simulations at alkaline pH fully reproduced experimental evidence as clusters did not form under those conditions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Medicinal
Maximiliano Martinez-Cifuentes, Emmanuel Soto-Tapia, Camila Linares-Pipon, Ben Bradshaw, Paulina Valenzuela-Hormazabal, David Ramirez, Patricio Munoz-Torres, Claudio Parra
Summary: This study proposes the design of beta-keto esters as antibacterial compounds. By synthesizing eight beta-keto ester analogues and conducting computational analysis, compound 8 was found to have the most promising potential. In vitro antimicrobial screening showed that compounds 6 and 8 exhibited the most promising activity against the panel of bacteria studied.
Article
Chemistry, Multidisciplinary
Nanako Tamai, Naoki Ogiwara, Eri Hayashi, Keigo Kamata, Toshiyuki Misawa, Takeru Ito, Tatsuhiro Kojima, Mireia Segado, Enric Petrus, Carles Bo, Sayaka Uchida
Summary: Cation-uptake has been extensively studied in materials science. In this study, the researchers focused on a molecular crystal composed of a charge-neutral polyoxometalate (POM) capsule and discovered the occurrence of cation-coupled electron-transfer reaction. The findings reveal the significance of the POM capsule in cation uptake.
Article
Chemistry, Physical
Diego Garay-Ruiz, Moises Alvarez-Moreno, Carles Bo, Emilio Martinez-Nunez
Summary: Computational description of reaction mechanisms can be greatly improved through automated chemical space exploration. The new Python library amk-tools simplifies the analysis of complex reaction networks by providing interactive dashboards and visualization tools. By applying this approach to the study of indole decomposition, new details of the reaction were discovered.
ACS PHYSICAL CHEMISTRY AU
(2022)
Article
Chemistry, Multidisciplinary
Diamantoula Maniaki, Diego Garay-Ruiz, Leoni A. Barrios, Daniel O. T. A. Martins, David Aguila, Floriana Tuna, Daniel Reta, Olivier Roubeau, Carles Bo, Guillem Aromi
Summary: This study successfully synthesized high-purity [LnLn'Ln] type molecules using a coordination chemistry scaffold and revealed their exceptional chemical selectivity through density functional theory calculations. The magnetic analysis and ab initio calculations suggest that these composite quantum gates have the potential to act as addressable, conditional multiqubit spin-based quantum gates. Furthermore, EPR analysis and pulsed experiments confirm the coherence and feasibility of these molecular systems.
