Search Results (113)

The synthesis of enantiomerically pure chiral β-nitroalcohols is a crucial objective in asymmetric catalysis. In order to efficiently obtain such chiral products, we developed a series of thermoresponsive, oxazoline–copper catalysts (Cu^II-PN_xFe_yO_z) via sequential reversible addition–fragmentation chain transfer (RAFT) polymerization. These catalysts can self-assemble in water into single-chain nanoparticles (SCNPs) with biomimetic behavior, in which intramolecular hydrophobic and metal-coordination interactions generate a confined hydrophobic cavity. Comprehensive characterization by FT-IR, TEM, DLS, CD, CA, and ICP analysis confirmed the nanostructure and composition. When applied to the aqueous-phase asymmetric Henry reaction between nitromethane and 4-nitrobenzaldehyde, the optimal catalyst (2.0 mol%) achieved a quantitative yield (96%) with excellent enantioselectivity (up to 99%) within 12 h. Furthermore, the thermosensitive poly(N-isopropylacrylamide, NIPAAm) block enabled facile catalyst recovery through temperature-induced precipitation above its lower critical solution temperature (LCST). This work presents an efficient and recyclable biomimetic catalytic system, offering a novel strategy for designing sustainable chiral catalysts for green organic synthesis. Full article

For those who did not follow the invention and development of enantioselective catalysis, this review introduces pertinent historical aspects of the field and presents the scientific concepts of asymmetric bio- and organocatalysis. They are powerful technologies applied in organic laboratories and industry. They realize chiral amplification by converting inexpensive achiral substrates and reagents into enantiomerically enriched products using readily recoverable solvents, if any are used. Racemic substrates can also be deracemized catalytically. More sustainable fabrications are now available that require neither toxic metallic species nor costly reaction conditions in terms of energy, atmosphere control, product purification, and safety. Nature has been the source of the first asymmetric catalysts (microorganisms, enzymes, alkaloids, amino acids, peptides, terpenoids, sugars, and their derivatives). They act as temporary chiral auxiliaries and lower the activation free energy of the reaction by altering the reaction mechanism. Reductions, oxidations, carbon-carbon and carbon-heteroatom bond-forming reactions are part of the process panoply. Asymmetric catalyzed multicomponent and domino reactions are becoming common. Typical modes of activation are proton transfers, hydrogen bonded complex formation, charged or uncharged acid/base pairing (e.g., σ-hole catalysts), formation of equilibria between achiral aldehydes and ketones with their chiral iminium salt or/and enamine intermediates, umpolung of aldehydes and ketones by reaction with N-heterocyclic carbenes (NHCs), phase transfer catalysis (PTC), etc. Often, the best enantioselectivities are observed with polyfunctional catalysts derived from natural compounds, but not always. They may combine to form chiral structures containing nitrogen, phosphorus, sulfur, selenium, and iodine functional moieties. Today, man-made enantiomerically enriched catalysts, if not enantiomerically pure, are available in both enantiomeric forms. Being robust, they are recovered and reused readily. 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

G-quadruplex (G4) DNA structures have recently emerged as promising chiral scaffolds for enantioselective catalysis. This study investigates how thymidine loop modifications influence the catalytic performance of the telomeric G4 sequence HT21 in the asymmetric sulfoxidation of thioanisole. To this end, several singly or doubly modified HT21 derivatives were synthesized by using β-L-2′-deoxythymidine, 5-hydroxymethyl-2′-deoxyuridine, and 5-bromo-2′-deoxyuridine instead of a T residue, or β-L-2′-deoxyadonesine instead of an A residue, in specific positions within the TTA loops. The catalytic activity of these analogues was evaluated in the Cu(II)-mediated oxidation of thioanisole using hydrogen peroxide as oxidant. All modified sequences maintained complete substrate conversion, but their enantioselectivities varied markedly. Whereas the highest enantiomeric excess (84% ee) had previously been achieved with the HT21 analogue bearing a β-L-2′-deoxyadenosine in the first loop, the thymidine-based modifications, either alone or in combination, resulted in lower ee values, suggesting that loop alterations critically affect the chiral microenvironment, not all loop positions are functionally equivalent, and single substitutions within the same loop can result in different enantioselectivities. These findings highlight new insights on how individual loop residues contribute to asymmetric induction and offer further details for tuning G4-based catalytic scaffolds. Full article

The Sakurai reaction constitutes a valuable tool for carbon–carbon bond formation. The use of nontoxic allylic reagents as well as the atom economy of the global process has prompted the development of enantioselective (aza)-variants based on the use of chiral organo- and metal catalysts. This review collects the recent developments in catalytic enantioselective Sakurai reactions published since the beginning of 2011, including methodologies based on the use of chiral organocatalysts, metal/boron catalysts and multicatalyst systems. It is divided into three parts, dealing successively with enantioselective organocatalytic (aza)-Sakurai reactions, enantioselective metal/boron-catalyzed Sakurai reactions and enantioselective multicatalyzed (aza)-Sakurai reactions. It shows that, although still widely developed with aromatic aldehydes, the enantioselective catalytic Sakurai reaction has considerably matured in the last decade. Full article

The Kabachnik–Fields (KF) reaction is a versatile three-component method for the condensation of amines, carbonyl compounds, and P–H reagents, enabling efficient synthesis of α-aminophosphonates—key bioactive and functional molecules. This review critically examines the literature from the last 25 years. However, with regard to mechanistic aspects, selected earlier seminal studies are also considered when necessary to provide a coherent and comprehensive mechanistic framework. Advances in catalyst-free methodologies, sustainable synthetic approaches, and Lewis and Brønsted acid catalysis are discussed, alongside developments in enantioselective KF reactions in the presence of chiral metal complexes or organocatalysts. Full article

Hydroxamic acids are emerging as versatile chiral ligands for metal-catalyzed asymmetric oxidations due to their tunable electronic and steric environments. In this study, we systematically compared the catalytic behavior of C₂- and C₁-symmetric hydroxamic acid ligands in the vanadium-catalyzed asymmetric epoxidation of allylic alcohols. A series of chiral hydroxamic acids (HA1–HA7) was synthesized and evaluated under varied conditions to elucidate the influence of ligand symmetry on enantioinduction and reactivity. The results demonstrate that C₂-symmetric bishydroxamic acids generate a highly organized chiral environment, leading to high enantioselectivity but often limited conversion, consistent with the Sabatier principle. Conversely, certain C₁-symmetric ligands—particularly HA3—produced notable enantioselectivity (up to 71% e.e.) and full conversion under optimized conditions with VO(OiPr)₃ in CH₂Cl₂. A quadrant-based stereochemical model is proposed to rationalize the differential performance of these ligands. These findings highlight the critical role of ligand desymmetrization in modulating the chiral environment around vanadium centers, providing valuable design principles for next-generation hydroxamic acid-based catalysts in asymmetric synthesis. The optimized system (VO(OiPr)₃/HA3 in CH₂Cl₂) afforded >99% conversion and 71% e.e., providing a basis for extending hydroxamic acid scaffolds to diverse allylic alcohols. Full article

Tungstophosphoric acid (TPA) has been supported on mesoporous silicas prepared using urea as the pore forming agent. The amount of urea (20, 30, or 40% w/w) influences the silica specific surface area (S_BET), total pore volume (Vp), and average pore diameter (Dp). The materials synthetized using 20% w/w (SiU20) display mainly mesoporous structures, with the highest Vp and Dp values being chosen to be used as TPA support. The SiU20-TPA solids with different TPA loadings (10, 20, or 30% w/w) have been used as supports for chiral copper catalysts with bis(oxazoline) or azabis(oxazoline) ligands. The catalytic efficiency of enantioselective cyclopropanation strongly depends on support morphology and TPA loading. SiU-TPA20 has been shown to be the optimal one. The stability of the complex is also a very important parameter, and the best results are obtained with an excess of chiral ligand to ensure the correct formation of the complex on the solid. In this way, with azabox-Cu/SiU20-TPA20 it is possible to obtain a highly selective (90% ee for the trans-cyclopropanes) and recoverable catalyst. Full article

This review updates the field of enantioselective copper-catalysed domino reactions promoted by chiral green copper catalysts, covering the literature since 2017. These complexes are derived from a diversity of chiral ligands, including mostly bisoxazolines and biphosphines along with monophosphines, N-heterocyclic carbenes, proline derivatives, phosphoric acids, phosphoramidates, and different types of N,N-ligands. The review shows that asymmetric copper catalysis, that suits the growing demand for greener processes, offers a real opportunity to replace toxic and expensive metals in the near future. Full article

Background: Carbohydrate-derived chiral ligands are promising tools in asymmetric catalysis due to their structural diversity, chirality, and availability. However, ligands based on galactose or sorbose have been scarcely explored in the enantioselective addition of dialkylzinc reagents to aldehydes. Methods: A series of chiral diols and β-amino alcohols was synthesized from methyl D-glucopyranoside, methyl D-galactopyranoside, and D-fructose. These ligands were tested in the titanium tetraisopropoxide-promoted enantioselective addition of diethylzinc to aromatic and aliphatic aldehydes. Results: Several ligands, particularly those with a D-fructopyranose backbone, exhibited excellent catalytic activity, with conversion rates up to 100% and enantioselectivities up to 96% ee. Notably, this study reports for the first time the use of β-amino alcohols derived from fructose and sorbose in this transformation. Conclusions: Carbohydrate-based ligands represent effective, inexpensive, and structurally versatile scaffolds for developing highly enantioselective catalysts, expanding the utility of sugars in asymmetric organometallic reactions. Full article

The efficient employment of chiral porous organic cages (POCs) for asymmetric catalysis is of great significance. In this work, we have synthesized a chiral N-rich organic cage constructed through chiral (S, S)-1,2-cyclohexanediamine and benzene-1,3,5-tricarbaldehyde utilizing dynamic imine chemistry according to the literature. Following reduction with NaBH₄, the resulting amine-based POCs (RCC3) feature appended chiral diamine moieties capable of coordinating Cu²⁺ cations. This Cu²⁺ coordination provides RCC3 with excellent enantioselectivity as a supramolecular nanoreactor in asymmetric decarboxylative Mannich reactions, providing up to 94% ee of the product. We found that the spatial distribution of chiral amine sites and the coordination of Cu²⁺ in the RCC3 have a significant impact on catalytic activity, especially enantioselectivity. This work provides insights into the structure–function relationship within supramolecular catalytic systems Full article

Axially chiral compounds play a pivotal role in organic synthesis, materials science, and pharmaceutical development. Among the various strategies for their construction, enantioselective iodination and bromination have emerged as powerful and versatile approaches, enabling the introduction of halogen functionalities that serve as valuable synthetic handles for further transformations. This review highlights recent advances in atroposelective iodination and bromination, with a particular focus on the synthesis of axially chiral biaryl and heterobiaryl frameworks. Key catalytic systems are discussed, including transition metal complexes, small-molecule organocatalysts, and high-valent metal catalysts in combination with chiral ligands or transient directing groups. Representative case studies are presented to elucidate mechanistic pathways, stereochemical induction models, and synthetic applications. Despite notable progress, challenges remain, such as expanding substrate scope, improving atom economy, and achieving high levels of regio- and stereocontrol in complex molecular settings. This review aims to provide a comprehensive overview of these halogenation strategies and offers insights to guide future research in the atroposelective synthesis of axially chiral molecules. Full article

A novel point-chiral six-membered cyclic phosphoric acid was synthesized starting from an enantiopure precursor via a concise three-step route. Its catalytic performance was evaluated in enantioselective three-component Mannich reactions. Under optimized conditions, the catalyst provided good yields and satisfactory enantiomeric excesses (up to 89%). The basic mechanism of the catalysis was also studied by the DFT method. Full article

Chiral covalent organic frameworks (COFs) hold great promise in heterogeneous asymmetric catalysis due to their designable structures and well-defined chiral microenvironments. However, precise control over the pore size of chiral COFs to optimize asymmetric catalytic performance remains challenging. Herein, we designed a proline-derived dihydrazide chiral monomer (L-DBP-Boc), which was subjected to Schiff-base reactions with two aromatic aldehydes of different lengths, 1,3,5-triformyl phloroglucinol (BTA) and 4,4′,4″-(1,3,5-triazine-2,4,6-triyl)tribenzaldehyde (TZ), to construct two hydrazone-linked chiral COFs with distinct pore sizes (L-DBP-BTA COF and L-DBP-TZ COF). Interestingly, the Boc protecting groups were removed in situ during COF synthesis. We systematically investigated the catalytic performance of these two chiral COFs in asymmetric aldol reactions and found that their pore sizes significantly influenced both catalytic activity and enantioselectivity. The large-pore L-DBP-TZ COF (pore size: 3.5 nm) exhibited superior catalytic performance under aqueous conditions at room temperature, achieving a yield of 98% and an enantiomeric excess (ee) value of 78%. In contrast, the small-pore L-DBP-BTA COF (pore size: 2.0 nm) showed poor catalytic performance. Compared to L-DBP-BTA COF, L-DBP-TZ COF demonstrated a 1.69-fold increase in yield and a 1.56-fold enhancement in enantioselectivity, possibly attributed to the facilitated diffusion and transport of substrates and products within the larger pore, thus improving the accessibility of active sites. This study presents a facile synthesis of pyrrolidine-functionalized chiral COFs and establishes the possible structure–activity relationship in their asymmetric catalysis, offering new insights for the design of efficient chiral COF catalysts. Full article

Enantioselective transition metal catalysis is undoubtedly a cornerstone at the frontier of chemistry, attracting intense interest from both academia and the pharmaceutical industry. Central to this field is the strategic utilization of noncovalent interactions (NCIs), including hydrogen bonding, ion pairing, and π-system engagements, which not only drive asymmetric synthesis but also enable precise stereochemical control in transition metal-catalyzed transformations. Recent breakthroughs have unveiled a new generation of rationally designed ligands that exploit ligand–substrate noncovalent interactions, emerging as indispensable tools for stereocontrolled synthesis and setting new paradigms in ligand engineering. These advancements establish a transformative framework for ligand engineering, bridging fundamental mechanistic insights with practical synthetic utility. In this review, the judicious design concepts and syntheses of novel ligands from the past five years were highlighted and their synthetic applications in asymmetric catalysis were detailed. Full article