Search Results (86)

The use of water as a nucleophile in catalytic asymmetric reactions remains a significant challenge, primarily due to its intrinsically low nucleophilicity and small size, which make precise control over both reactivity and stereoselectivity particularly difficult. To address this issue, we developed a CPA-catalyzed asymmetric hydrolysis system, successfully achieving the efficient and highly stereoselective transformation of 4H-oxazines with water. Under this catalytic system, the initial formation of chiral α-bromo ketones is followed by their in situ conversion through reduction and intramolecular S_N2 reactions, directly affording valuable chiral bromo alcohols and chiral oxazolone derivatives in high yields with excellent enantioselectivity. Full article

Over the last 20 years, Deep-Eutectic Solvents (DES) have been making a significant impact in the field of chemistry, with applications in nanotechnology, biomass transformation, electrochemistry pharmaceuticals and a host of other applications that includes catalysis. Considering the importance of chiral organocatalysis for the selective synthesis of drugs, pharmaceuticals and fragrances, etc. DESs were quickly harnessed as the media for carrying out organocatalytic transformations. In this review, we discuss some of the most important examples from the literature that have made an impact in the field over the last 5 years. A more recent development has been the incorporation of DESs in structured and self-organized gel-like assemblies that are known as EutectoGels. These soft structures offer a more defined and compact environment that can influence stereoselectivity by pre-organizing the reactants in three-dimensional space, and potential control the types of transition states that can be formed. Full article

Enzymatic cascades, defined here as multi-enzymatic sequences operating on a shared reaction pathway and inspired by the spatial and temporal organization of metabolism, have emerged as powerful and versatile tools for sustainable organic synthesis. They minimize intermediate isolation, enhance atom economy and ensure outstanding chemo-, regio- and stereoselectivity, providing efficient alternatives to conventional multistep routes. Here, we highlight the conceptual role of substrate channeling, minimal cells, artificial metabolism and enzyme promiscuity in the translation of enzymatic cascades into synthetic strategies. Special attention is focused on advanced immobilization on functional and renewable supports, which enhance stability and recyclability and introduce new ways for thermodynamic and kinetic control. Hybrid systems integrating enzymes with photocatalysis, electrochemistry and chemical modules expand the catalytic repertoire far beyond biology. Complementary tools in bioinformatics, structural modeling and artificial intelligence may also enable pathway balancing, predictive design and dynamic optimization. Applications span from the valorization of renewable feedstocks to the synthesis of privileged scaffolds and fine chemicals. Full article

Apart from in hydrosilylation, platinum has traditionally played a limited role in homogeneous catalysis due to its high thermodynamic stability and lower intrinsic reactivity compared to other group 10 metals. However, the emergence of N-heterocyclic carbene (NHC) ligands has substantially broadened the catalytic profile of transition metals by enabling access to new mechanistic pathways and enhancing robustness under demanding conditions. This review summarizes advances in Pt–NHC catalysis reported between 2010 and 2025. These transformations encompass hydrosilylation of amides and CO₂, hydroboration and diboration, hydroamination, alkyne hydration, hydrogenation, selective alkyne dimerization, Suzuki–Miyaura coupling, arene C–H borylation, and cycloisomerization reactions, in which NHC ligands enhance bond activation, control regio- and stereoselectivity, and stabilize reactive Pt intermediates, including chiral architectures, enabling high enantioselectivity. Full article

Density functional theory (DFT) calculations at the M06-2X-D3/6-311++G(2df,2pd) level elucidate the mechanism and selectivity origins in the NHC-catalyzed divergent synthesis of spirocyclopentane oxindoles from isatin-derived enals and N-sulfonyl ketimines. The Michael addition constitutes the regio- and stereoselectivity-determining step, where Parr function analysis demonstrates that nucleophile/electrophile electrophilicity governs regioselectivity, while distortion/interaction and non-covalent interaction analyses reveal stereoselectivity is controlled by distortion and weak interactions. K₃PO₄ facilitates Breslow intermediate formation and proton transfer toward the β-lactam-fused spirocyclopentane oxindole, whereas N,N-diisopropylethylamine (DIPEA) promotes these processes for the spirocyclopentane oxindole bearing an enaminone moiety. Catalyst roles are also further delineated. Full article

The Reformatsky reaction, first reported in 1887, has long been recognized as a fundamental method for carbon–carbon bond construction due to its mild conditions and functional group tolerance. Over the past few decades, this transformation has undergone a notable revival, with modern catalytic variants addressing limitations of stoichiometric protocols and expanding its role in complex molecule synthesis. Yet, despite its versatility, achieving stereoselective control remains a longstanding challenge. Herein we report the use of dichlorocyclopentadienyltitanium(III) (CpTiCl₂), generated in situ from CpTiCl₃ and manganese, as an efficient catalyst for Reformatsky-type couplings of aldehydes with α-haloesters and α-iodonitriles. Under mild conditions, CpTiCl₂ promotes the formation of β-hydroxy esters in high yields and with significant diastereoselective preference for the syn isomer (up to 100:0 syn:anti). This behavior contrasts sharply with the poor or anti-selective outcomes previously observed with titanocene(III) chloride (Cp₂TiCl). Mechanistic analysis suggests that the unique steric and electronic environment of CpTiCl₂—characterized by enhanced Lewis acidity and increased coordination vacancies—favors a Zimmerman–Traxler-type transition state that enforces syn stereocontrol. The methodology tolerates a wide variety of substrates, including aliphatic and aromatic aldehydes as well as α-iodonitriles, extending the scope of titanium-mediated Reformatsky chemistry. These findings establish CpTiCl₂ as a sustainable, selective, and robust organotitanium catalyst for stereoselective carbon–carbon bond formation, providing a promising alternative to the Nugent reagent and paving the way for new applications in complex molecule synthesis. Full article

Sugar amino acids (SAAs) represent a privileged class of molecular chimeras that uniquely merge the structural rigidity of carbohydrates with the functional display of amino acids. These hybrid molecules have garnered significant attention as programmable conformational constraints, offering a powerful strategy to overcome the inherent limitations of peptide-based therapeutics, such as proteolytic instability and conformational ambiguity. The strategic incorporation of SAAs into peptide backbones, particularly within cyclic frameworks, allows for the rational design of peptidomimetics with pre-organized secondary structures, enhanced metabolic stability, and improved physicochemical properties. This review provides a comprehensive analysis of the synthetic methodologies developed to access the diverse structural landscape of SAAs, with a focus on modern, stereoselective strategies that yield versatile building blocks for peptide chemistry. A critical examination of the structural impact of SAA incorporation reveals their profound ability to induce and stabilize specific secondary structures, such as β- and γ-turns. Furthermore, a comparative analysis positions SAAs in the context of other widely used peptidomimetic scaffolds, highlighting their unique advantages in combining conformational control with tunable hydrophilicity. We surveyed the application of SAA-containing cyclic peptides as therapeutic agents, with a detailed case study on gramicidin S analogs that underscores the power of SAAs in elucidating complex structure–activity relationships. Finally, this review presents a forward-looking perspective on the challenges and future directions of the field, emphasizing the transformative potential of computational design, artificial intelligence, and advanced bioconjugation techniques to accelerate the development of next-generation SAA-based therapeutics. Full article

A series of Zn complexes containing guanidine– and amidine–phenolate ligands were synthesized and evaluated as catalysts for the polymerization of rac-lactide at 130 °C, under solvent-free conditions, giving rate constants in the range of 0.71–4.37 × 10^–4 s^–1. Polymerization under identical conditions with the guanidine– and amidine–phenol proligands themselves used as catalysts gave values in the range of 0.30–2.45 × 10^–4 s^–1. The stereoselective production of polylactic acid from either the Zn complexes or the proligands was limited (P_r = 0.47–0.62). The molecular weight of the polymers was lower than expected for living polymerizations due to chain transfer and/or transesterification but were comparable to those obtained in control experiments with Sn(Oct)₂. Full article

This study reports an improved diastereoselective synthesis of substituted spiro[chromane-2,4′-pyrimidin]-2′(3′H)-ones via the acid-catalyzed condensation of 6-styryl-4-aryldihydropyrimidin-2-ones with resorcinol, 2-methylresorcinol, and pyrogallol. The optimized method allows for the isolation of diastereomerically pure products, with stereoselectivity controlled by varying acid catalysts (e.g., methanesulfonic acid vs. toluenesulfonic acid) and solvent conditions. The synthesized compounds were evaluated for antimicrobial and antioxidant activities. Notably, the (2S*,4R*,6′R*)-diastereomers exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacterial strains with minimal inhibition concentration down to 2 µg/mL, while derivatives containing vicinal bisphenol moieties demonstrated potent antioxidant activity, with IC₅₀ values (12.5 µg/mL) comparable to ascorbic acid. Pharmacokinetic analysis of selected hit compounds revealed favorable drug-like properties, including high gastrointestinal absorption and blood-brain barrier permeability. These findings highlight the potential of spirochromane-pyrimidine hybrids as promising candidates for further development in the treatment of infectious diseases and oxidative stress-related pathologies. Full article

Fluorinated organic molecules have become indispensable in modern chemistry, owing to the unique properties imparted by fluorine to other compounds, including enhanced metabolic stability, controlled lipophilicity, and improved bioavailability. The site-selective incorporation of fluorine atoms into organic frameworks is essential in pharmaceutical, agrochemical, and material science research. In recent years, catalytic fluorination has become an important methodology for the efficient and selective incorporation of fluorine atoms into complex molecular architectures. This review highlights advances in catalytic fluorination reactions over the past six years and describes the contributions of transition metal catalysts, photocatalysts, organocatalysts, and electrochemical systems that have enabled site-selective fluorination under a variety of conditions. Particular attention is given to the use of well-defined fluorinating agents, including Selectfluor, N-fluorobenzenesulfonimide (NFSI), AlkylFluor, Synfluor, and hypervalent iodine reagents. These reagents have been combined with diverse catalytic systems, such as AgNO₃, Rh(II), Mo-based complexes, Co(II)-salen, and various organocatalysts, including β,β-diaryl serine catalysts, isothiourea catalysts, and chiral phase-transfer catalysts. This review summarizes proposed mechanisms reported in the original studies and discusses examples of electrophilic, nucleophilic, radical, photoredox, and electrochemical fluorination pathways. Recent developments in stereoselective and more sustainable protocols are also examined. By consolidating these strategies, this article provides an up-to-date perspective on catalytic fluorination and its impact on synthetic organic chemistry. Full article

Recent advances in zinc complexes for stereoselective ring-opening polymerization (ROP) and copolymerization (ROCOP) highlight their pivotal role in synthesizing biodegradable aliphatic polyesters and polycarbonates. These materials address the urgent demand for sustainable alternatives to petroleum-based plastics, with stereochemical control directly impacting polymer crystallinity, thermal stability, and degradability. Zinc catalysts, leveraging low toxicity and versatile coordination chemistry, enable precise stereoregulation, whose performance is modulated by ligand steric/electronic effects, coordination geometry, and reaction conditions. This review summarizes the recent developments in zinc complexes for stereoselective ROP and ROCOP, focusing on ligand design strategies to enhance catalytic performance. Full article

A stereoselective and scalable strategy for the synthesis of phosphorus-containing bicyclic and tricyclic compounds from 1-phenylphosphin-2-en-4-one 1-oxide is presented. This activated dienophile, available in both racemic and enantiopure forms, undergoes smooth [4+2] cycloadditions with acyclic and cyclic dienes, affording products with excellent yields and controlled stereochemistry. Notably, the cis/trans-fusion of the cycloadducts (phosphadecalones and phosphahexahydrochrysene) can be selectively controlled by fine-tuning the conditions of microwave-assisted cycloaddition reaction. The influence of temperature, time, and steric effects on cis/trans and endo/exo selectivity was examined in detail. The molecular structure, including the absolute configuration, of eight products has been determined by X-ray crystallography. These analyses further established the endo-selective nature of the cycloaddition, favoring the P=O face of the dienophile. Post-cycloaddition transformations of selected P-stereogenic phosphadecalone, such as isomerization, reduction and deoxygenation, demonstrate the synthetic versatility of the resulting products. Full article

Quinazolinones, a class of nitrogen-containing heterocyclic compounds, occupy a crucial position in medicinal chemistry and materials science due to their significant application potential. In recent years, the catalytic asymmetric synthesis of axially chiral quinazolinones has emerged as a prominent research area, driven by their prospective applications in the development of bioactive molecules, design of chiral ligands, and fabrication of functional materials. This review comprehensively summarizes recent advancements in the catalytic asymmetric synthesis of axially chiral quinazolinones, with a particular focus on the construction strategies for the three major structural types: the C–N axis, N–N axis, and C–C axis. Key synthetic methodologies, including atroposelective halogenation, kinetic resolution, condensation–oxidation, and photoredox deracemization, are discussed in detail. In addition, the review provides an in-depth analysis of the applications of various catalytic systems, such as peptide catalysis, enzymatic catalysis, metal catalysis, chiral phosphoric acid catalysis, and others. Despite the substantial progress made thus far, several challenges remain, including the expansion of the substrate scope, enhanced control over stereoselectivity, and further exploration of practical applications, such as drug discovery and asymmetric catalysis. These insights are expected to guide future research towards the development of novel synthetic strategies, the diversification of structural variants, and a comprehensive understanding of their biological activities and catalytic functions. Ultimately, this will foster the continued growth and evolution of this rapidly advancing field. Full article

Axially chiral structures have become increasingly common in modern materials and pharmaceuticals, especially as chiral ligands and organocatalysts, highlighting their growing significance. In the field of pharmaceutical research, there are several notable examples worth highlighting, such as the antibiotics vancomycin, Knipholone, and Mastigophorene A. Over the past decade, the availability of axially chiral compounds has significantly improved through advancements in existing strategies and the introduction of modern catalytic atroposelective synthesis concepts. These synthetic advancements not only broaden the scope of chemical reactions, but also facilitate the construction of axially chiral frameworks with high application value. Currently, various synthetic methods are available for achieving stereoselective synthesis of axially chiral compounds under catalyst control, including desymmetrization, (dynamic) kinetic resolution, cross-coupling reactions, and de novo ring-forming synthesis. This paper focuses on recent advances in constructing atropisomers through palladium-catalyzed asymmetric cyclization strategies. Full article

Pesticides, essential for controlling pests and weeds, significantly boost agricultural productivity. However, their excessive use leads to substantial contamination of environmental matrices, including soil and water. Organophosphorus compounds, which constitute more than 30% of the global use of insecticides and herbicides, are particularly concerning, and their widespread application raises alarms among environmentalists and regulatory agencies due to their high toxicity to aquatic organisms. Therefore, to avoid the spread of these compounds within the environment, the contaminated sites may be treated with various methods. This study explored a soil detoxification procedure utilizing gaseous ozone. As a representative of organophosphorus pesticides, chlorfenvinphos was utilized as soil contaminant. This compound is still reported to occur in a number of environmental matrixes. The method used in this study involved the exposure of the soil matrix in a fluidized state to an ozone-enriched atmosphere. The ozonation procedure enabled the removal of the pesticide from the soil matrix. During its oxidation, some degradation products were detected; in particular, they included 2,4-dichlorobenzoic acid and 2-chloro-1-(2,4-dichloro-phenyl)-ethanone, whose presence was confirmed by a GC-MS system and the NIST database. However, they also underwent degradation. Moreover, on the basis of stereoselective reaction of Z and E isomers, the pesticide degradation pathway was proposed. Additionally, the efficacy of this detoxication method was evaluated using a combination of chronic and acute toxicity tests, employing Eisenia foetida earthworms as bioindicators. On the basis of the obtained results, it can be concluded that organophosphorus herbicides containing unsaturated bonds in their structure, including glyphosate, can be removed using this method. Full article