Propargylic substitution is a broadly studied basic reaction but requires a vicinal leaving group in the alkyne substrate. Here, we describe the first asymmetric remote substitution of alkynes bearing a linear alkyl-linked remote leaving group via synergistic Pd/amine catalysis. A set of modified diamine organocatalysts guarantees the high regio-, geometry- and enantioselectivity of the remote coupling between alkynes and aldehydes, during which conventionally more competitive hydrofunctionalization process is completely inhibited. Scale-up test and various derivatizations show the reliability and value of the protocol. Mechanistic studies suggest that the formation of crucial 1,3-diene intermediate from alkyne and a complex redox pathway of Pd metal are involved in the catalytic cycle.

We report the development of a class of chiral pincer ruthenium (PCNOx)Ru complexes bearing oxazoline-based PCNOx ligands for the asymmetric cyclopropanation of olefins with alpha-diazo carbonyl compounds. These catalysts exhibit high reactivity and stereoselectivity across a broad range of substrates, including monosubstituted, 1,1-disubstituted, and challenging trisubstituted olefins. The present catalyst showed superior performance in the asymmetric intermolecular cyclopropanation of trisubstituted olefins compared to the known (Pheox)Ru catalyst.

Dynamic, reversible recognition converts binding events into resolvable NMR signatures, providing a powerful route to selective detection. This review surveys design principles and recent advances in recognition-enabled NMR detection, emphasizing 19F-, 31P-, and 1H-based probes that leverage coordination chemistry to transduce analyte binding into chemical-shift, line-shape, or relaxation changes. 19F-labeled metal complexes-featuring Pd, Pt, Al, and Ga centers-offer modular structures, broad analyte scope, and clean baselines for multi-component analysis and chiral discrimination, while amphiphilic constructs enable measurements under physiological conditions. Para-hydrogen-induced polarization and SABRE/SABRE-SHEATH synergize with these probes to overcome sensitivity limits, enabling trace-level detection and rapid, mixture-compatible readouts, including heteronuclei and long-lived states. We compare exchange-regime control (slow vs fast), proximity/ through-space effects, and substituent engineering that enlarge detection windows and sharpen resolution, and we outline automated workflows that couple orthogonal probes with simple shift databases. Looking forward, key opportunities include expanding coverage to weakly coordinating oxygenates, improving biocompatibility and stability, integrating hyperpolarization under mild conditions, and unifying probe libraries with machine-readable outputs for high-throughput, AI-assisted analysis in asymmetric synthesis, metabolomics, reaction monitoring, and diagnostics.

In modern natural product synthesis, chemists are often able to execute two or even multiple chemical reactions to occur in one pot by designing substrate structures and screening reaction conditions, thus to synthesize target molecules in a concise and efficient manner. Such a reaction sequence is termed a cascade reaction. Michael addition and aldol reaction are the two most applied classic reactions in organic synthesis. By regulating the reaction conditions and designing the substrates, they can occur successively in the same system to form complex cyclic systems. This cascade reaction is termed Michael/aldol cascade cyclization reaction, which can effectively improve the atomic and step economy of a synthesis. This review comprises more than 40 reported studies on natural product synthesis as examples to summarize nine common types of Michael/aldol cascade cyclization reactions, to demonstrate their applications as key steps in complex natural product synthesis, and to outlook on the direction of further developments of this methodology.

Different from well-known 1,4- and 1,6-conjugate addition reactions, umpolung 1,5-addition is considered electronically mismatched and is rarely explored. With palladium hydride catalysis, 1,5-addition was recently proved to be feasible. Diverse types of C-, O-, and N-based nucleophiles can be enantioselectively introduced to the gamma-position of electron-deficient conjugated dienes. A series of privileged cyclic structures can also be conveniently prepared through 1,5-addition-involved cascade processes with high stereocontrol. This article provides a perspective on the concept development and advancement of 1,5-conjugate addition, which has gradually emerged as a new synthetic model.

Herein, we report a chiral Br & oslash;nsted-acid-catalyzed dearomatization of quinolines. The reaction proceeds via dearomative hydride transfer and subsequent enantioselective semipinacol rearrangement. The key to this reaction sequence is to guide the imine intermediate to a rearrangement pathway other than over-reduction. Utilizing a bulky chiral imidodiphosphorimidate catalyst guarantees the desired reactivity. A series of chiral spiro tetrahydroquinoline products is afforded in good yields (up to 93%) and enantioselectivity (up to 93% ee). Detailed mechanistic insights are obtained based on DFT calculations.

The construction of highly efficient visible-light-excitable afterglow materials based on thermally activated delayed fluorescence (TADF) mechanism is reported, employing an intramolecular charge transfer technology. The resulting TADF-type afterglow materials exhibit emission lifetimes in the range of hundreds of milliseconds and photoluminescence quantum yields of approximately 50%, demonstrating remarkable temperature-responsive properties. By introducing additional electron-donating groups into the donor-acceptor (D-A)-type difluoroboron beta-diketonate (BF2bdk) molecules, donor-acceptor-donor (D-A-D)-type compounds were designed. These compounds exhibit a moderate rate of reverse intersystem crossing (RISC), thereby promoting the emergence of TADF-type afterglow within a rigid crystalline matrix. Furthermore, the D-A-D design approach elevates the highest occupied molecular orbital (HOMO) energy level, enabling TADF-type afterglow emission under visible light excitation. The research findings highlight the significance of intramolecular charge transfer technology in advancing the design of high-performance organic TADF-type afterglow materials.

Hydrofunctionalization of unsaturated hydrocarbons via transition metal catalysis is a powerful route to prepare allyl skeletons, but is limited to mono-and two-component transformation models. Here we describe a novel protocol for the unprecedented three-component hydrofunctionalization via in situ formed diene species. Both amines and stabilized carbon nucleophiles undergo the assembled hydrofunctionalization with various olefins and alkenyl bromides through Pd-catalyzed tandem Heck coupling and outer-sphere allylation, generating allylic C-N and C-C bonds in reasonable yields and with excellent regioselectivities. In particular, the combination of assembled hydrofunctionalization and following derivatizations enables new access to a series of valuable substituted cyclic skeletons. Preliminary mechanistic studies support the in situ formation of critical conjugated diene intermediate for sequential hydrofunctionalization (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Phosphodiesterase-5 (PDE5A) is a critical therapeutic target for treating male erectile dysfunction (ED). PDE5A inhibitors like sildenafil are clinically effective, but exhibit side effects due to non-specific inhibition of related PDE isoforms. This necessitates the discovery of safer and specific PDE5A inhibitors. The prepared folium of Epimedium sagittatum (PFES) is a primary sovereign drug in traditional Chinese medicine (TCM) formulations for ED. As part of ongoing research into its pharmacodynamic basis, this study isolated and identified forty-four flavonoids and organic acids from PFES. The inhibitory activities of these compounds against PDE5A were systematically evaluated, and three compounds (1, 5, and 6) are demonstrated to have significant PDE5A inhibition activities. Notably, the compound 6 (baohuoside I), was previously confirmed the activity with PDE5A, and its co-crystal structure with PDE5A was also reported. To elucidate the molecular mechanisms underlying the inhibition of PDE5A by compound 1 and 5, we solved the crystal structures of the catalytic domain of PDE5A in complex with compound 1 and 5. Further structural analyses revealed distinct binding modes adopted by 1 and 5 for occupying the PDE5A active site, highlighting their specific interactions with PDE5A compared to each other and to other established inhibitors like sildenafil. In summary, these findings underscore the potential of PFESderived natural compounds as specific PDE5A inhibitors, and provide crucial insights for the rational development of novel ED therapeutics with potentially improved specificity and reduced side effects based on TCM constituents.

Here, we report the preparation of a series of dihydrosilole derivatives via a Pd-catalyzed Heck-type reaction by employing arylthianthrenium salts as the arylating reagent. The reaction features mild conditions, excellent functional group and heterocycle tolerance, thus providing a general approach for the construction of 2,3-dihydrosiloles in high efficiency. Notably, the new protocol could be further applied to the late-stage installation of silacycles in bioactive complexes via site-selective thianthrenation and a sequential Pd-catalyzed Heck-type coupling reaction.

Constructing new Br & ouml;nsted acid sites within zeolitic materials holds paramount importance for the advancement of solid-acid catalysis. Zeo-type germanosilicates, a class of metallosilicates with a neutral framework composed of tetravalent Ge and Si oxygen tetrahedrons, are conventionally considered not to generate Br & ouml;nsted acid sites. Herein, we disclose an abnormal phenomenon with Ge-rich IWW-type germanosilicate (IWW-A) as an example that Ge-enriched germanosilicates are featured by mild Br & ouml;nsted acidity. Using the art-of-state density functional theory calculation, 19F magic angle spinning nuclear magnetic resonance, microcalorimetric and ammonia infrared mass spectrometry-temperature-programmed desorption characterizations, the nature of germanosilicate's Br & ouml;nsted acidity has been demonstrated to be closely related to the neighboring framework Ge-hydroxyl pairs. Besides, the contribution of Ge-OH groups to Br & ouml;nsted acidity and the role of Ge-pair structure for maintaining mild acid strength have been elucidated. In catalytic cracking of n-hexane and methanol-to-olefins reaction, the IWW-A germanosilicate exhibit high light olefins selectivity, good recyclability and low carbon deposition, outperforming the benchmark zeolite catalyst, ZSM-5 aluminosilicate. (c) 2025, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

GABA (g-aminobutyric acid) transporter 3 (GAT3) is primarily found in glial cells and is essential for regulating GABA homeostasis in the central nervous system by mediating GABA uptake. Consequently, GAT3 has emerged as a significant therapeutic target for the treatment of epilepsy. In this study, we present the cryoelectron microscopy (cryo-EM) structures of GAT3 bound to its substrate GABA, the selective inhibitor SNAP-5114, and in the substrate-free state. GAT3 binds to GABA in an inward-facing conformation, while SNAP-5114 occupies the GABA-binding pocket and is stabilized by extensive interactions with surrounding residues. Functional studies reveal that E66 plays a pivotal role in determining the substrate-binding mode and specificity of SNAP-5114 binding. Taken together, our study clarifies the GABA binding mechanism of GAT3 and reveals the molecular basis for the specific inhibition of SNAP-5114, offering valuable insights for developing GAT3 subtypes selective inhibitors, which hold potential as a treatment for epilepsy.