Article
Chemistry, Multidisciplinary
Martin Berger, Davide Carboni, Paolo Melchiorre
Summary: The study presents the first catalytic enantioselective conjugate addition of allyl groups to alpha, beta-unsaturated aldehydes, utilizing the visible-light-excitation of chiral iminium ions to activate allyl silanes toward the formation of allylic radicals. This radical mechanism overcomes issues seen in traditional conjugate allylation processes and selectively installs prenyl fragments at the beta-carbon of enals.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
En Li, Jiean Chen, Yong Huang
Summary: The Michael reaction is an important method for preparing functional molecules with a β-stereogenic center. However, the enantioselective seleno-Michael addition is still poorly explored. In this study, a highly enantioselective Michael addition reaction of alkyl selenols to enones was reported, introducing a Se atom asymmetrically to an electron-deficient double bond. A chiral bifunctional N-heterocyclic carbene (NHC)/thiourea catalyst was developed and showed remarkable selectivity in delivering chiral β-seleno ketones.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Viktoria Kozma, Zsolt Szakonyi, Gyorgy Szollosi
Summary: This study reveals the structural effects of beta-amino acids on the asymmetric Michael additions, including the impact of substituent bulkiness on selectivity, the beneficial arrangement of functional groups in cis isomers, and the influence of nitrogen substituents on reaction rate and enantioselectivity.
Article
Chemistry, Applied
Laura A. Bryant, Kenneth Shankland, Hannah E. Straker, Callum D. Johnston, Nicholas R. Lees, Alexander J. A. Cobb
Summary: The article describes a rare organocatalytic intramolecular cyclization of resorcinols with a high enantioselectivity using a specific organocatalyst. The obtained bicyclic resorcinols show excellent utility in the synthesis of cannabinoid-like compounds, and exhibit anticonvulsant activity.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Multidisciplinary
Si-Jia Liu, Zhi-Han Chen, Jia-Yi Chen, Shao-Fei Ni, Yu-Chen Zhang, Feng Shi
Summary: A new class of axially chiral styrene-based thiourea tertiary amine catalysts with efficient synthetic route, multiple chiral elements, and multiple activating groups has been designed. These catalysts have proven to be efficient in enabling the cyclization reaction of 2-benzothiazolimines and homophthalic anhydrides with high yields and excellent stereoselectivities. The role of axially chiral styrene moiety in controlling reactivity and enantioselectivity has been elucidated through theoretical calculations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Amol B. Gorde, Anas Ansari, Ramesh Ramapanicker
Summary: New molecules were designed and synthesized to improve the catalytic ability of the catalyst, resulting in high catalytic activity and stereoselectivity under optimized conditions. The studies showed high yields of Michael adducts with excellent enantioselectivities and diastereoselectivities in a wide range of aldehydes and beta-nitrostyrenes.
Article
Chemistry, Applied
Xiao Lin, Keli Ge, Ningning He, Xuling Chen, Pengfei Li, Mingxin Dong, Wenjun Li
Summary: A chiral phosphoric acid-catalyzed enantioselective aza-addition reaction of arylamines with ketimines has been developed, resulting in the construction of chiral acyclic N,N-acetal motifs. The reaction proceeds smoothly under standard conditions, yielding a series of acyclic N,N-acetals in 82-99% yield with 80-96% ee.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Applied
Irma Garcia-Monzon, Jorge Borges-Gonzalez, Tomas Martin
Summary: The heterogenization of homogeneous catalysts onto a solid support is a crucial step towards sustainable chemistry. In this study, we developed a series of polymer-supported tetrahydropyran-based hybrid dipeptides as active catalysts for the enantioselective Michael addition of aldehydes to beta-nitrostyrenes. The optimal anchor position and orientation between the catalyst and solid support, as well as the linker length, were carefully designed to enhance the catalytic efficiency. These supported catalysts exhibited high yields and enantiomeric excesses, and detailed deactivation studies provided important insights for prolonging their useful life.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Applied
Andrea Guerrero-Corella, Miguel A. Valle-Amores, Alberto Fraile, Jose Aleman
Summary: An asymmetric organocatalytic aza-Michael addition reaction of ketimines to nitroolefins is described, utilizing 2-hydroxybenzophenone imine to improve the enantioselective addition of N-centered nucleophiles to nitroalkenes. The versatility of the process is demonstrated under both batch and flow conditions, resulting in the synthesis of a wide variety of nitroamine derivatives with excellent yields and enantioselectivities. Additionally, this methodology was successfully applied to the formal synthesis of VNI, a drug-like scaffold for the treatment of Chagas disease.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Applied
Eugenia Marques-Lopez, Isaac G. Sonsona, Miryam Garces-Marin, M. Concepcion Gimeno, Raquel P. Herrera
Summary: In this study, the potential of phosphites as nucleophiles for the asymmetric synthesis of chiral chromene derivatives was explored. By employing asymmetric organocatalyzed phospha-Michael addition, chiral chromenylphosphonates were synthesized using a bifunctional squaramide. The optimized protocol provided good reactivity with yields of up to 95% and chiral products with an enantiomeric excess of up to 98%.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Biochemistry & Molecular Biology
Jae Ho Shim, Seok Hyun Cheun, Hyeon Soo Kim, Deok-Chan Ha
Summary: The study utilized thiourea as an organocatalyst to promote enantioselective Michael addition reaction between isobutyraldehydes and maleimides in water, achieving high yield and enantioselectivity. The solvent effect was explained by theoretical calculations suggesting the participation of a hydrogen bond activated CF3 substituent of the catalyst by surrounding water molecules, enabling low catalyst loading in organic reactions of chiral substances for pharmaceutical applications.
Article
Chemistry, Physical
Fangfang Guo, Jiean Chen, Yong Huang
Summary: Recently, chiral N-heterocyclic carbenes (NHCs) have been established as powerful catalysts for enantioselective bond-forming processes via noncovalent interactions. A bifunctional NHC with an embedded hydrogen-bonding motif has been reported in this study, showing remarkable tolerance of various Michael acceptors in an asymmetric aza-conjugate addition reaction, with catalytic efficiency far exceeding that of the benchmark tertiary amine-thiourea scaffold.
Article
Chemistry, Multidisciplinary
Vasilis Tseliou, Adriana Faraone, Laura Kqiku, Jan Vilim, Gianluca Simionato, Paolo Melchiorre
Summary: This study introduces a novel strategy for biocascades using a single multifunctional enzyme to promote multiple stereoselective steps in a domino process by mastering distinct catalytic mechanisms, simplifying the synthesis of chiral molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Da Xu, Yu Chang, Yidong Liu, Wenling Qin, Hailong Yan
Summary: This study achieved the enantioselective construction of stable VQM intermediates through organocatalyzed bromination, and revealed the mechanistic details of the two sequential events in VQM-involved reactions. The high potential of VQM as axially chiral synthetic reagents in organic chemistry was demonstrated.
Review
Chemistry, Organic
Yulia A. Trukhanova, Nikita M. Chernov, Elena V. Kuvaeva, Igor P. Yakovlev
Summary: Six-membered heterocyclic systems, such as glutarimides, are widely used in medicinal chemistry due to their wide range of bioactivity. The synthesis of C,N-highly functionalized glutarimides is an important topic in modern organic synthesis as it allows for the construction of more complex systems and expands the range of various drugs. This review discusses approaches to the synthesis of N- and C-functionally-substituted glutarimides presented in the literature from 2005 to 2022, including the enantioselective synthesis of spiroglutarimides, the use of organocatalysis in glutarimide synthesis, and optimization of the synthesis of known pharmaceuticals.
SYNTHESIS-STUTTGART
(2023)
Review
Chemistry, Organic
Ivana Nemethova, Radovan Sebesta
Summary: The search for mild, user-friendly, easily accessible, and robust organometallic reagents is crucial in organometallic chemistry. New methodologies involving organometallics should ideally be practical for syntheses of target compounds. Organometallic compounds such as organozirconium reagents, generated via hydrozirconation of alkenes or alkynes with the Schwartz reagent, have proven to be convenient in various reactions including conjugate additions, allylic substitutions, cross-coupling reactions, and additions to carbonyls or imines. Moreover, the Schwartz reagent itself serves as a useful reducing agent for polar functional groups.
SYNTHESIS-STUTTGART
(2021)
Article
Chemistry, Organic
Patricia Cmelova, Denisa Vargova, Radovan Sebesta
Summary: A bifunctional organocatalysis combining covalent and noncovalent activation is introduced in this study, using a hybrid peptide-thiourea catalyst for promoting asymmetric Michael additions of aldehydes to challenging nitroalkenes. The catalyst can be utilized under solvent-free conditions, and its structure and mode of action are elucidated through spectroscopic and density functional theory studies.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Tibor Penaska, Vitalii Palchykov, Erik Rakovsky, Gabriela Addova, Radovan Sebesta
Summary: The stereoselective formation of spiro oxindole pyrrolidines via formal [3+2] cycloaddition of oxindole imines with ketoesters and ketoamides was investigated, with bifunctional squaramide organocatalyst inducing enantioselectivity of up to 72% ee. Ketoamides provided alternative products, and the reaction pathway was elucidated with the help of DFT calculation.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Inorganic & Nuclear
Ambroz Almassy, Andrea Hejtmankova, Denisa Vargova, Radovan Sebesta
Summary: Ferrocene-containing phosphorus derivatives play a crucial role as ligands in transition-metal catalysis. The synthesis of ferrocene-based phosphanes from corresponding phosphinites via retro-phospha-Brook rearrangement was investigated, revealing intramolecular isomerization and rearrangement mechanisms.
JOURNAL OF ORGANOMETALLIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Viera Polackova, Dominika Kristofikova, Boglarka Nemethova, Renata Gorova, Maria Meciarova, Radovan Sebesta
Summary: Bifunctional N-sulfinylureas and thioureas with an appended pyrrolidine unit were synthesized and evaluated as organocatalysts in Michael additions. The N-sulfinyl-urea catalyst was more efficient than the corresponding thiourea, achieving up to 98% ee enantioselectivities for some substrates. The mode of action was elucidated through DFT calculations, confirming a dual activation mode involving enamine activation of aldehydes and hydrogen-bond activation of nitroalkenes.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Tibor Penaska, Viktoria Modrocka, Klara Stankovianska, Maria Meciarova, Erik Rakovsky, Radovan Sebesta
Summary: This study achieves enantioselective and diastereoselective synthesis of densely substituted chiral pyran derivatives by using amino-thiourea or quinine organocatalyst under ball-milling conditions. Liquid-assisted grinding proves to be a highly efficient means of obtaining pyrans in high yield, with high enantiomeric purities and short reaction times.
Article
Chemistry, Organic
Eva Veverkova, Pavlina Molnosiova, Radovan Sebesta
Summary: This study involved the Michael addition-cyclization reaction of 2-(2-nitrovinyl)phenol with two different reactive Michael donors to produce chiral benzopyran derivatives. Bifunctional amino-squaramides containing one or two chiral units were evaluated as catalysts, and the use of green solvents as reaction media was investigated. The best result was achieved using methyl-cyclopentanone-2-carboxylate as the Michael donor in ethyl (-)-L-lactate with a quinine-based amino-squaramide catalyst.
Editorial Material
Chemistry, Organic
Radovan Sebesta
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Patricia Cmelova, Peter Sramel, Barbora Zahradnikova, Viktoria Modrocka, Henrich Szabados, Maria Meciarova, Radovan Sebesta
Summary: This paper presents the synthesis and evaluation of a bifunctional organic catalyst that can efficiently catalyze the selective synthesis of polyfunctional molecules. The hybrid organocatalysts consist of Pro-Pro dipeptide and thiourea moiety connected via a 1,2-diaminocyclohexane unit.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Tomas Carny, Tibor Penaska, Samuel Andrejcak, Radovan Sebesta
Summary: In this article, a mechanochemical Pd-catalyzed cross-coupling reaction method is introduced, allowing the synthesis of target molecules with high yields at ambient temperature and atmosphere. This method is operationally simple, shortens reaction time, and tolerates various functional groups, making it applicable to large-scale synthesis and has been applied in pharmaceutical synthesis.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Organic
Peter Kisszekelyi, Tibor Penaska, Klara Stankovianska, Maria Meciarova, Radovan Sebesta
Summary: In this study, the synthesis and utilization of derivatives of 4H-benzo[b][1,4]thiazine-3-carboxylic acid were presented. These benzothiazine compounds were synthesized through the coupling reaction of aminothiols and bromopyruvates, and the oxidative dimerization of the starting materials was observed. Furthermore, the coupling of benzothiazines with amino acids enabled the enantioselective synthesis of the nonproteinogenic amino acid 2-amino-3-propylhexanoic acid.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Samuel Andrejcak, Peter Kisszekelyi, Michal Majek, Radovan Sebesta
Summary: Arylboronates are important in organic synthesis, and this study presents an efficient mechanochemical method to synthesize them from arene diazonium salts. Notably, the presence of sodium chloride significantly enhances this transformation, possibly by promoting the decomposition of diazonium salts through anion exchange. Chloride anions also contribute to the formation of a strongly reducing Cl-B anion radical intermediate that promotes a radical chain reaction. The addition of a small amount of polar solvent as a liquid-assisted grinding additive improves the efficiency of the reaction. Quantum chemical calculations support the proposed mechanism.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Brigita Mudrakova, Renata Marcia de Figueiredo, Jean-Marc Campagne, Radovan Sebesta
Summary: We describe a stereoselective tandem reaction involving the asymmetric conjugate addition of dialkylzinc reagents to unsaturated acylimidazoles followed by trapping of the intermediate zinc enolate with carbocations. Chiral NHC ligands were used to generate chiral zinc enolates with high enantiomeric purities, which were then reacted with highly electrophilic onium compounds to yield densely substituted acylimidazoles. DFT calculations provided insights into the reactivity of the zinc enolates derived from acylimidazoles and allowed comparison with metal enolates obtained from other conjugate addition reactions.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Review
Chemistry, Organic
Peter Kisszekelyi, Radovan Sebesta
Summary: Metal enolates are indispensable intermediates and building blocks in many organic synthetic transformations. This review focuses on chiral metal enolates obtained by asymmetric conjugate additions of organometallic reagents, which are complex intermediates that can be employed in various transformations. The review also highlights the efforts to expand the reactivity of metal enolates with new electrophiles and provides information on their applications in total synthesis.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Tomas Carny, Radovan Sebesta
Summary: Chiral ferrocene derivatives with a planar stereogenic unit are important for their applications as chiral catalysts and materials. The main method to obtain 1,2-disubstituted planarly chiral ferrocenes is base-mediated ortho-metalation using organolithium bases. This methodology has been used to synthesize a variety of chiral ligands and useful compounds. Newer methodologies involving transition-metal-catalyzed C-H bond activation strategies provide access to different types of planar chiral ferrocene derivatives.
