Review
Chemistry, Multidisciplinary
Tasneem Elkoush, Natasha D. Reich, Michael G. Campbell
Summary: In the past two decades, there has been a significant increase in the number of synthetically useful transformations catalyzed by silver, with dinuclear silver species commonly emerging as a key feature in these reactions. Understanding the role of dinuclear silver complexes in homogeneous catalysis can aid in the development of improved design principles for silver catalysts.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Marta Gil-Ordonez, Camille Aubry, Cristopher Nino, Alicia Maestro, Jose M. Andres
Summary: A series of N-Boc ketimines derived from pyrazolin-5-ones have been successfully used as electrophiles in enantioselective Mannich reactions with different 1,3-dicarbonyl compounds. The reaction enables the synthesis of 4-amino-5-pyrazolone derivatives with diverse structures, including the beta-diketone and pyrazolinone substructures. The use of a quinine-derived bifunctional squaramide as an organocatalyst with a very low loading proves to be highly effective in terms of yield and enantioselectivity. The obtained products can be further transformed into enantioenriched diheterocyclic systems, which show potential as drug candidates.
Article
Chemistry, Multidisciplinary
Hirotsugu Suzuki, Sora Kondo, Koichiro Yamada, Takanori Matsuda
Summary: A novel copper-catalyzed diastereo- and enantioselective reductive Mannich-type reaction was developed in this study, providing a direct and scalable synthetic method for enantioenriched beta(2,3,3)-amino acids with vicinal stereogenic centers. The protocol shows excellent synthetic utility and scalability.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Applied
An-Qi Miao, Meng Zhou, Jing-Long Chen, Shi-Chao Wang, Wen-Juan Hao, Shu-Jiang Tu, Bo Jiang
Summary: An asymmetric addition of arylboronic acids to pyrazolinone ketimines was reported using a palladium/chiral N,N'-disulfonyl bisimidazoline (Bim) catalytic system, yielding enantioenriched 4-amino-5-pyrazolones with high yields and high enantiomeric excess. The reaction demonstrated excellent compatibility between pyrazolinone ketimines and arylboronic acids, providing an enantioselective access to chiral aza-heterocycles bearing alpha-tertiary amines.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Chihiro Homma, Masahiro Yamanaka, Taichi Kano, Keiji Maruoka
Summary: A facile and practical synthesis of alkynyl Z-ketimines has been developed, serving as a synthetic equivalent of alkyl ketimines. The obtained alkynyl Z-ketimines have been successfully utilized in enantioselective Mannich reaction and conjugate addition catalyzed by a chiral amine with an acid functionality.
Article
Chemistry, Applied
Xue-Qi Wang, Fang-Fang Feng, Jing Nie, Fa-Guang Zhang, Jun-An Ma
Summary: An asymmetric decarboxylative Mannich reaction of phosphonate sultam-ketimines with malonic acid half esters is achieved using saccharide-derived bifunctional amino thiourea catalysis. This reaction provides access to a wide range of alpha-amino-beta-carboxylic phosphonates with N,P-containing tetrasubstituted stereocenters, achieving high enantioselectivity (78-99% ee). Further synthetic derivatizations can introduce amide, alcohol, and azetidine scaffolds to the core structures.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Sirisuk Keereewan, Chutima Kuhakarn, Pawaret Leowanawat, Saowanit Saithong, Vichai Reutrakul, Darunee Soorukram
Summary: A convenient and efficient synthetic strategy for the preparation of enantioenriched gem-difluoromethylenated spiro-pyrrolidinyl and spiro-piperidinyl oxindoles is described. The key step involved the fluoride-mediated diastereoselective nucleophilic addition of PhSCF2SiMe3 to chiral N-tert-butanesulfinyl ketimines, which provided separable diastereomeric adducts. Removal of the chiral sulfinyl group and structural manipulation yielded the desired chiral gem-difluoromethylenated spiro-pyrrolidinyl and spiro-piperidinyl oxindoles.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Applied
Kazuki Ogura, Tsunayoshi Takehara, Takeyuki Suzuki, Shuichi Nakamuraa
Summary: A novel enantioselective vinylogous Mannich reaction was developed for the synthesis of acyclic delta-amino-alpha,beta-unsaturated carbonyl compounds, achieving excellent yields and enantioselectivities using a specific catalyst. This study provides an efficient route for the synthesis of compounds in this specific category.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Multidisciplinary
Akira Saito, Shinya Adachi, Naoya Kumagai, Masakatsu Shibasaki
Summary: The strategic use of a sterically demanding Ni-II pincer carbene complex has enabled high enantioselectivity in the direct catalytic asymmetric addition of acetonitrile to aldehydes, resulting in highly enantioenriched beta-hydroxynitriles. This highly atom-economical process offers a promising pathway for utilizing inexpensive acetonitrile as a C2 building block in practical synthetic toolbox for asymmetric catalysis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Applied
Gabriele Lupidi, Alessandro Palmieri, Marino Petrini
Summary: N-Activated ketimines are characterized by electron-withdrawing groups linked to the nitrogen atom, enhancing the electrophilic character and allowing addition reactions with weak nucleophiles. The presence of oxygen atoms in these groups is crucial for asymmetric catalytic reactions. This review summarizes the literature on the synthesis of optically active alpha-substituted amino derivatives using open-chain N-activated ketimines.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Review
Chemistry, Organic
Yeming Wang, Chaoqun Zhang, Shizhe Li, Lihui Liu, Xiaodong Feng, Gang Liu
Summary: In recent years, the efficiency and selectivity of silver-catalyzed and silver-promoted isocyanide reactions have drawn much attention due to their ability to form diverse new bonds. This review highlights the recent progress in the synthesis of five-membered heterocyclic compounds, six-membered heterocyclic compounds, fused cyclic compounds, and linear nitrogen-containing compounds.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Applied
I-Ting Chen, Ren-You Guan, Jeng-Liang Han
Summary: In this study, a catalytic asymmetric vinylogous Mannich/annulation/acylation reaction was developed for the synthesis of chiral spiro-oxindole piperidine derivatives with polyaromatic scaffolds. The reaction provided the desired products in good yields and high enantioselectivity. DFT computational calculations were used to explain the mechanism and origin of the observed enantioselectivity and O-acetylated products.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Jingdong Wang, Yuxin Liu, Zhonglin Wei, Jungang Cao, Dapeng Liang, Yingjie Lin, Hai-feng Duan
Summary: A series of chiral thiourea compounds with multiple H-bond donors derived from hydroquinine have been reported. The aza-Henry reaction of isatin-derived ketimines and long-chain nitro-alkanes catalyzed by these chiral thioureas shows high enantioselectivity and excellent diastereoselectivity. This work represents the first report on long-chain nitroalkanes as substrates with excellent diastereoselectivity in metal-free catalytic systems.
Article
Chemistry, Multidisciplinary
Jing Cao, Antonia Seitz, Jose A. Forni, Anastasios Polyzos, David W. Lupton
Summary: This article reports on a reaction design that avoids the facile oxidation of phosphine organocatalyst and combines traditional nucleophilic phosphine organocatalysis with photoredox catalysis to enable Giese coupling with ynoates. The approach exhibits good generality, and its mechanism is supported by cyclic voltametric, Stern-Volmer quenching, and interception studies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Wen-Tian Zeng, Xiao Han, Gong-Bin Huang, Jiang Weng, Albert S. C. Chan, Gui Lu
Summary: An enantioselective reductive coupling of nitrobenzyl bromides with cyclic ketimines was achieved via a synergistic combination of N-heterocyclic carbene (NHC) catalysis and nickel catalysis utilizing a single-electron-transfer (SET) process. This method overcomes the limitation of homoenolate radical species, enabling tight stereocontrol of the nitrobenzyl radical intermediate and providing a direct and facile route to previously inaccessible, enantioenriched 4-substituted 4-aminopyrazolones and 3-substituted 3-aminooxindoles. Furthermore, this NHC/metal cooperative catalysis opens up new reaction pathways, particularly in asymmetric radical reactions.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Devenderan Ramanathan, Qinglong Shi, Meichen Xu, Rui Chang, Beatriz Penin, Ignacio Funes-Ardoiz, Juntao Ye
Summary: We report a photochemical approach for the asymmetric deuterosilylation of exocyclic olefins using mannose-derived thiols as the chiral catalyst and inexpensive deuterium oxide as the deuterium source. DFT computational studies show that multiple non-covalent interactions between the thiol catalyst and the radical adduct are responsible for controlling the enantioselectivity of the reaction.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Applied
Gaspard Hedouin, Racha Abed Ali Abdine, Quentin Dherbassy, Christophe Michon, Ignacio Funes-Ardoiz, Francoise Colobert, Joanna Wencel-Delord
Summary: In this study, we reported the design of original enantiopure dissymmetrical diphosphines, BiaxPhos, bearing two atropisomeric axes. BiaxPhos ligands possess unique chiral architecture and important modularity, making them attractive candidates for asymmetric catalysis. The Ir-BiaxPhos catalyzed asymmetric imines hydrogenation exhibited excellent enantioselectivities and mild reaction conditions. Remarkably, experimental mechanistic investigations and DFT calculations revealed an unexplored mechanistic scenario involving the hydrogenation of the enamine tautomeric form rather than the classic reduction of the imine.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Ranjana Bisht, Mihai V. Popescu, Zhen He, Ameer M. Ibrahim, Giacomo E. M. Crisenza, Robert S. Paton, David J. Procter
Summary: Activated benzothiophenes undergo C-H/C-H-type coupling with phenols to give C4 arylation products without a directing group or a metal catalyst. Quantum chemical calculations propose a stepwise mechanism involving aryloxysulfur species cleavage and addition of phenoxonium cation to C4 position. The metal-free arylation process demonstrates varied selective manipulation of benzothiophene products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Nil Sanosa, Diego Ambrosi, Pedro Ruiz-Campos, Diego Sampedro, Ignacio Funes-Ardoiz
Summary: Formation of carbon-carbon bonds through cross-coupling reactions using readily available substrates, like alcohols, is crucial for modern organic chemistry. Recently, direct alkyl alcohol functionalization has been achieved by the use of N-Heterocyclic Carbene (NHC) salts via in situ formation of an alcohol-NHC adduct and its activation by a photoredox catalyst to generate carbon-centered alkyl radicals. Experimental observations show that only electron deficient NHC activators work, but the reasons for this behavior are not well understood. In this study, a DFT computational approach is used to investigate the mechanism of alcohol activation using up to seven NHC salts, providing insights into the influence of their electronic properties on alkyl radical formation. The results reveal that the electron-richness of the NHC salt plays a crucial role in determining the success of the transformation.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Matthew A. Horwitz, Alexander B. Durr, Konstantinos Afratis, Zijun Chen, Julia Soika, Kirsten E. Christensen, Makoto Fushimi, Robert S. Paton, Veronique Gouverneur
Summary: The controlled programming of regiochemical outcomes in nucleophilic fluorination reactions with alkali metal fluoride is achieved through two synergistic approaches exploiting hydrogen bonding catalysis. The charge density of fluoride is modulated with a hydrogen-bond donor urea catalyst to influence the kinetic regioselectivity in the fluorination of dissymmetric aziridinium salts. Additionally, a urea-catalyzed formal dyotropic rearrangement is reported, allowing access to enantioenriched fluoroamine regioisomers and providing new opportunities in regiodivergent asymmetric (bis)urea-based organocatalysis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Owen Smith, Mihai V. Popescu, Madeleine J. Hindson, Robert S. Paton, Jonathan W. Burton, Martin D. Smith
Summary: This paper reports the design, synthesis and characterization of a helically chiral triaryloxonium ion that functions as a determinant of configuration. It is the only example of a chiral non-racemic and configurationally stable molecule in which the oxygen atom is the sole stereogenic centre.
Article
Chemistry, Organic
Khadijah Anwar, Francisco Jose Aguilar Troyano, Ayham H. Abazid, Oumayma El Yarroudi, Ignacio Funes-Ardoiz, Adrian Gomez-Suarez
Summary: Here, we present a highly modular strategy for synthesizing spirocyclic scaffolds from easily available starting materials, such as cyclic ketones and alpha-amino or oxamic acids. The reaction involves a simple Knoevenagel condensation, followed by a cascade Giese-type reaction and base-mediated cyclization, resulting in a wide range of polar spirocyclic products in high yields. Our method allows for easy diversification of the products, thus providing rapid access to libraries of potential drug-like molecules.
Article
Chemistry, Physical
Peng Zhang, Chang-Qiu Guo, Wang Yao, Chuan-Jun Lu, Yingzi Li, Robert S. S. Paton, Ren-Rong Liu
Summary: A palladium-catalyzed amination method was developed to construct structurally diverse N-C atropisomers, and the reaction mechanism was explained using density functional theory calculations. This method has a broad substrate scope, high stereoselectivity, a simple catalytic system, good functional group tolerance, and dynamic kinetic resolution.
Article
Chemistry, Multidisciplinary
Juan V. Alegre-Requena, Sowndarya S. Shree, Raul Perez-Soto, Turki M. Alturaifi, Robert S. Paton
Summary: AQME is a free and open-source Python package for automated workflows in cheminformatics and quantum chemistry. It integrates tasks across multiple computational chemistry packages and data formats, preserving computational protocols, data, and metadata for access and reuse. AQME has a modular structure and can be used by researchers familiar with Python.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Jingyang Qin, Manuel Barday, Samikshan Jana, Nil Sanosa, Ignacio Funes-Ardoiz, Christopher J. Teskey
Summary: A mild and selective hydropyridylation method for dienes was reported, allowing for traceless coupling of dienes on a wide range of pyridine substrates. The method showed good functional group tolerance, making it suitable for late-stage functionalization. The mechanistic pathway involved non-reversible hydrogen atom transfer, resulting in a reaction that was uniquely selective for dienes in the presence of other olefins.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Jeong-Yu Son, Santeri Aikonen, Nathan Morgan, Alexander S. Harmata, Jesse J. Sabatini, Rosario C. Sausa, Edward F. C. Byrd, Daniel H. Ess, Robert S. Paton, Corey R. J. Stephenson
Summary: Cuneane, a strained hydrocarbon, can be accessed via metal-catalyzed isomerization of cubane. It has a polyhedral structure with six faces of different shapes. The rigidity and unique properties make it a potential scaffold for the synthesis of small molecules and materials. However, previous synthetic efforts have been limited to monosubstituted or redundantly substituted cuneanes, and more complex substitution patterns are needed for the study of this ring system in various applications.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Calum Patel, Emy Andre-Joyaux, Jamie A. Leitch, Xabier Martinez de Irujo-Labalde, Francesco Ibba, Job Struijs, Mathias A. Ellwanger, Robert Paton, Duncan L. Browne, Gabriele Pupo, Simon Aldridge, Michael A. Hayward, Veronique Gouverneur
Summary: This article introduces a method of reacting acid-grade fluorspar with dipotassium hydrogen phosphate under mechanochemical conditions, resulting in a solid product suitable for forming sulfur-fluorine and carbon-fluorine bonds.
Editorial Material
Chemistry, Physical
Pablo Garrido-Barros, Ignacio Funes-Ardoiz
Summary: A molecular ruthenium catalyst has been developed to selectively generate hydrazine, which overcomes the thermodynamic challenges.
Article
Chemistry, Multidisciplinary
S. V. Shree Sowndarya, Yeonjoon Kim, Seonah Kim, Peter C. St. John, Robert S. Paton
Summary: This study advances the accuracy and applicability of machine learning in predicting bond dissociation energy by expanding and updating the model. The new model includes more elements and bond types, and successfully improves predictive accuracy by introducing more training data, which is of great significance for the application of molecules in medicine and the environment.
Article
Chemistry, Multidisciplinary
Alberto Gimenez-Gomez, Benjamin Rollins, Andrew Steele, Helen Holzel, Nicolo Baggi, Kasper Moth-Poulsen, Ignacio Funes-Ardoiz, Diego Sampedro
Summary: Solar energy utilization has gained attention for its abundance and renewability. Developing energy storing compounds that capture and release solar energy on demand is a potential solution. These compounds undergo a photochemical transformation, storing solar energy in high-energy photoisomers. While the photoisomerization of MOlecular Solar Thermal (MOST) systems has been extensively studied, the back-conversion using heterogeneous catalysts is still underexplored. In this study, the performance of 27 catalysts in releasing stored energy in a Norbornadiene/Quadricyclane MOST system is compared using UV-Vis spectroscopy. The findings provide insights for the development of effective catalysts in MOST systems and highlight the importance of further investigation on heterogeneous catalysis.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)