An iron-mediated direct chalcogenation of tyrosine-containing peptides has been developed. This protocol operates under mechanochemical conditions and exhibits broad functional group tolerance. Furthermore, the synthetic utility of this protocol was demonstrated by the late-stage functionalization of pharmaceutical compounds. Preliminary mechanistic studies indicated that a radical pathway is likely to be operative.

The construction of spiro-iminoindoline-pyrazolines from readily available starting materials has garnered significant interest within the synthetic chemistry community. Herein, we report a chemo- and diastereoselective (2 + 3) and three-component formal (1 + 1 + 3) cascade cyclization strategy for their synthesis, demonstrating unprecedented CC chemoselectivity of nitrile imines toward α,β-unsaturated imines. This method delivers multifunctionalized products efficiently under mild conditions. Furthermore, preliminary antioxidant screening using the DPPH radical scavenging assay highlights their potential bioactivity.

Here, we present a highly regioselective chalcogenation of pyridines, pyrimidines, and isoquinolines using readily available dichalcogenides. This transformation operates under simple conditions, tolerates a wide range of functional groups, and renders these processes applicable to the late-stage functionalization of drugs. Preliminary mechanistic studies indicated that a single-electron transfer (SET) pathway is likely involved in this chalcogenation reaction.

A copper‐mediated intramolecular cyclization of o ‐bromoenaminone with elemental sulfur has been developed, providing efficient access to thiochromones. This transformation features a broad substrate scope, affording C2/C3‐unsubstituted thiochromones in moderate to excellent yields with good functional group tolerance. Furthermore, the established copper‐mediated protocol was applied to the late‐stage functionalization of bioactive molecules. Preliminary mechanistic studies suggest that the reaction proceeds via ortho thiolation with elemental sulfur followed by intramolecular cyclization.

The pursuit of high enantioselectivity remains a central challenge in the burgeoning area of radical N-heterocyclic carbene (NHC) catalysis. Moreover, direct functionalizations of unstrained and unpolarized C─C bonds continue to pose a formidable obstacle in organocatalysis. Herein, we disclose an asymmetric NHC organocatalytic platform that achieves highly enantioselective radical acylation of inert C(sp2)─C(sp3) bonds. Central to this advance is the development of a previously unknown collection of chiral thiazolium catalysts integrating medium-ring backbones with C2-symmetric chiral units, which facilitate the stereoselective acylation of C─C bonds through a Smiles-type rearrangement. This organocatalytic protocol affords more than 70 examples with outstanding yields (up to 99%) and excellent regioselectivity (up to 99:1 rr) and enantioselectivity (up to 99.5:0.5 er) under transition metal-free and light-free conditions. The practicality of this strategy is further underscored by stereo-controlled late-stage functionalization of complex bioactive molecules. Mechanistic insights from combined experimental and computational studies support a radical-mediated catalytic cycle and elucidate the origin of enantioselectivity.

Developing efficient methods for the deconstructive nitrogenation of alkenes remains challenging because carbon-carbon double bonds are generally resistant to cleavage under mild conditions. Here we report a catalyst-free, water-promoted deconstructive amination of electron-deficient dienes that proceeds through an unprecedented single-carbon deletion pathway. The transformation operates smoothly in water without photoirradiation, oxidants, or radical precursors, providing diverse fully substituted pyrroles. Mechanistic studies indicate a sequence involving initial aziridination followed by water-assisted C-C and C-N bond cleavage of a transient aziridine intermediate. Water plays a key role in enabling single-carbon extrusion and guiding selective skeletal reorganization. This approach offers high atom- and step-economy and complements existing oxidative and radical-based strategies. The mild conditions, broad substrate scope, and straightforward access to bioactive pyrrole analogs highlight the practical utility of this method. Overall, this work provides a mechanistically distinct route to carbon-carbon double bond deconstructive nitrogenation and expands the toolkit for heterocycle synthesis.

Abstract Arene difunctionalization offers a powerful strategy for the simultaneous installation of two functional groups in a single step. Despite recent advances, ipso / para -selective arene transformations remain underdeveloped. Herein, we report an N -heterocyclic carbene (NHC)-catalyzed radical protocol that addresses this challenge. The process features a unique generation of acyl-inserting Smiles rearrangement, wherein radical Meisenheimer intermediates are intercepted by NHC-bound radicals prior to rearomatization. Subsequent ketone deprotonation regenerates ionic Meisenheimer intermediates, thereby completing the rearrangement and affording 1,4-difunctionalized arenes. This organocatalytic protocol exhibits broad substrate scope, tolerates diverse functional groups, and delivers acylated aniline derivatives in excellent yields (96 examples, up to 98% yield). The synthetic potential is further showcased by a ring-expansion strategy to benzo[ b ]azepines and by late-stage functionalization of drug-like molecules. Mechanistic insights from combined experimental and computational studies shed light on the unique reactivity and the observed excellent site-selectivity.

Axially chiral arylpyrroles are a promising class of compounds with broad applications in catalysis, medicinal chemistry, and materials science. Herein, we report a copper-catalysed dynamic kinetic asymmetric (4 + 1) cyclization for the atroposelective synthesis of arylpyrroles bearing a single stereogenic axis or 1,2-diaxes from 1,3-enynes and amines. This dynamic kinetic asymmetric transformation employs a chiral Cu/Pybox complex, with air as the oxidant and DABCO serving as both a base and a proton shuttle. A key feature is the reversibility of the aza-Michael addition, which enables the dynamic formation/cleavage of distal C-N bonds. The 5-endo-dig cyclization serves as both the rate-determining and stereodetermining step, ensuring precise stereocontrol of the proximal stereocenters by the catalyst. This strategy overcomes long-standing challenges in the stereocontrol of distal C-N bond formation and enables the synthesis of atropisomeric DMAP catalysts with two stereogenic axes. DFT calculations provide insights into the mechanism of stereocontrol.

The catalytic asymmetric activation of sterically hindered functionalized aldehydes remains a significant challenge, especially when using traditional covalent activation strategies. In this study, we present an alternative noncovalent enolate activation strategy to address this issue. Specifically, we utilized various a-halogenated aldehydes-alpha-fluoro, alpha-chloro, and alpha-bromo aldehydes-as latent enolates to achieve a highly enantioselective aza-[4 + 2] cyclization. This Bro.nsted base organocatalytic protocol facilitates the asymmetric synthesis of a broad spectrum of highly functionalized, halogenated isothioureas, delivering high yields and enantioselectivities under mild conditions. Furthermore, we successfully performed several synthetic transformations to enhance the structural diversity of the chiral isothiourea products. Additionally, density functional theory (DFT) calculations rationalize the observed diastereo- and enantioselectivity.

Achieving diastereoconvergence in synthetic chemistry, particularly in photocatalytic radical systems, remains a significant yet challenging goal. Herein, we report a diastereoconvergent radical boroacylation enabled by cooperative N-heterocyclic carbene (NHC) and photocatalysis. Notably, the reaction consistently delivers syn-diastereoselective products, regardless of the starting alkene geometry-E, Z, or an E/Z mixture-demonstrating its diastereoconvergent nature. In contrast, when the conformational dynamics are restricted, as in the case of a rigid cyclic Z-alkene, the reaction yields the anti-diastereoisomer, providing diastereoconvergence of mechanistic support for the key role of the rotational flexibility of the intermediate alkyl radical. This protocol enabled efficient synthesis of over 50 examples of β-boryl ketones in good to excellent yields, with complete regioselectivity and diastereoselectivity. The broad applicability of this method is further underscored by its successful adaptation to the late-stage functionalization of drug-derived NHC-boranes. Mechanistic studies, including control experiments, photophysical measurements, kinetic investigations, and density functional theory (DFT) calculations, revealed the organocatalytic radical reaction pathway and provided insights into the origins of diastereoselectivity and kinetic behavior.

The morphology and compositional modulation of palladium-based nanomaterials are of paramount importance in enhancing the catalytic performance of the ethanol oxidation reaction (EOR). In this study, we employed a simple oil bath method to synthesize PdBi alloy nanoparticles (NPs), maintaining the same elemental ratio. The size of the NPs could be modulated by varying the surfactant dosage. The synthesized PdBi alloys exhibited alterations in the d-band center of Pd, which were attributed to strain and ligand effects. These alterations subsequently affected the adsorption energy of the catalyst surface for the reaction intermediates. The current density of the Pd9Bi/200 NP in the ethanol oxidation reaction was found to be as high as 1042.0 mA mg-1, which is approximately twice that of Pd/C (508.0 mA mg-1). This enhanced activity can be attributed to the modification of the electronic structure and morphology, which enables the material to possess a larger electrochemically active surface area (ESCA), thus providing a substantial number of active sites for the catalytic reaction. Furthermore, the experimental data indicated that increasing the electrocatalytic temperature, pH, and ethanol concentration could accelerate the electrooxidation rate of the EOR. This study presents an effective approach for investigating the role of surfactants in the synthesis of nanomaterials and enhancing the activity and stability of noble metal catalysts.

Isoflavonoids represent a privileged scaffold among various bioactive natural products, rendering their structural diversification through green synthesis and subsequent biological evaluations a compelling research area. In this study, an NHC organocatalytic radical acylalkylation of 1,3-enynes using salicylaldehydes is presented, followed by a cascade intramolecular annulation, yielding a series of fluorinated isoflavone derivatives with substantial yields under environmental-friendly conditions. This approach, distinguished by its excellent modularity and high functional group tolerance, represents an unprecedented organocatalytic 1,3,4-trifunctionalization of 1,3-enynes designed for the green synthesis of bioactive isoflavones in a single step. Furthermore, it is demonstrated that these synthesized fluorinated isoflavonoids effectively suppress proliferation in breast cancer cells, with the most potent compound 8 also inhibiting migration in MDA-MB-231 cells.

A general and efficient approach to the synthesis of various indole-fused δ-sultones has been developed via DBU-mediated [3+3] cyclizations of indolin-3/2-ones and β-(hetero)arylethenesulfonyl fluorides. Notably, the reaction shows a broad substrate scope, and over 70 examples were exhibited in up to 99% isolated yield. In addition, some of the synthesized compounds showed significant antitumor activity against HepG2 and Caco-2 cells in vitro, which might provide promising insights for the future discovery and rational design of novel antitumor agents.

image [5187‐82‐6] C 6 H 13 BrO 2 S (MW 229.14) InChI = 1S/C6H13O2S.BrH/c1‐4‐8‐6(7)5‐9(2)3;/h4‐5H2,1‐3H3;1H/q+1;/p‐1 InChIKey = JXFPTJYKYKVENJ‐UHFFFAOYSA‐M (used as a stabilized precursor of sulfur ylide reagent for the cycloaddition reaction) Physical Data: mp 86–88 °C. 1 Solubility: soluble in H 2 O, insoluble in some organic solvents, such as hexane. Form Supplied in: white crystalline powder. Analysis of Reagent Purity: spectroscopic data: IR v 675, 694, 1133, 1364, 1395, 1525, 1621, 1656, 2923, 2976, 3326 cm −1 1 and NMR. 1 H NMR (400 MHz, CDCl 3 ) δ 4.93 s (2 H , SCH 2 ), 4.12 q (2 H , CH 2 CH 3 ), 3.33 s [6 H , (CH 3 ) 2 S], 1.16 t (3 H , CH 3 CH 2 ), 13 C (100 MHz, CDCl 3 ) δ 163.76 (CO), 63.43 (OCH 2 ), 36.51 (SCH 2 ), 25.20 [(CH 3 ) 2 S], 14.21 (CH 3 CH 2 ). 2 Preparative Method: a solution of ethyl bromoacetate in acetone or DMSO was stirred under nitrogen, and dimethyl sulfide was added in one portion (eq 1). 1 A white precipitate started to appear immediately and became thicker upon stirring. After stirring for 6–18 h at room temperature, the solid was filtered, washed with acetone, and dried under vacuum to afford the sulfonium salt as white crystals. image Handling, Storage, and Precautions: (2‐ethoxy‐2‐oxoethyl) dimethyl sulfonium bromide is a white solid and stable to air. The solid can be stored in a dry and well‐ventilated place and should be protected from moisture.

Spirocyclic tetrahydroquinolines (spiro-THQs) and tetrahydroisoquinolines (spiro-iTHQs), along with their derivatives constitute a prominent class of natural products, which exhibit a broad spectrum of biological activities. Due to their pharmacological importance, a series of asymmetric methods were developed for constructing these frameworks. The present review offers a comprehensive and up-to-date overview of recent advances in the enantiostereoselective synthesis of these frameworks, aiming to provide a reference guide and an inspiration source for researchers in organic synthesis and drug discovery.

Achieving selective functionalization of distal C-H bonds, particularly remote aromatic C(sp(2))-H bonds, is a formidable challenge in organic synthesis. Recently, we have developed an innovative para-selective acylation strategy that targets ultra-remote aryl C(sp(2))-H bonds located eight bonds away from an activation site, utilizing radical N-heterocyclic carbene (NHC) organocatalysis. This method is based on a novel single-electron pathway, enabling site-selective activation of aryl C-H bonds through generated nitrogen-centered radicals in situ. This approach shows immense potential for the functionalization of pharmaceuticals, amino acids, and peptides, underscoring its importance in medicinal chemistry. 1 Introduction 2 Our Strategy of Ultra-Remote Activation via NHC Organocatalysis 3 Features and Applications of the NHC-Catalytic Ultra-Remote Acylation 4 Conclusion and Perspectives

Achieving selective functionalization of distal C–H bonds, particularly remote aromatic C(sp 2)–H bonds, is a formidable challenge in organic synthesis. Recently, we have developed an innovative para-selective acylation strategy that targets ultra-remote aryl C(sp 2)–H bonds located eight bonds away from an activation site, utilizing radical N-heterocyclic carbene (NHC) organocatalysis. This method is based on a novel single-electron pathway, enabling site-selective activation of aryl C–H bonds through generated nitrogen-centered radicals in situ. This approach shows immense potential for the functionalization of pharmaceuticals, amino acids, and peptides, underscoring its importance in medicinal chemistry. 1 Introduction 2 Our Strategy of Ultra-Remote Activation via NHC Organocatalysis 3 Features and Applications of the NHC-Catalytic Ultra-Remote Acylation 4 Conclusion and Perspectives

This advanced organic chemistry laboratory course is specifically designed for senior undergraduate students, focusing on molecular skeleton editing for new drug discovery. By using state-of-the-art light-driven scaffold editing, the course facilitates the conversion between six-membered nitrogen heterocycles and five-membered heterocycles, showcasing the significant advantages of molecular scaffold editing over traditional drug synthesis methods. The curriculum provides comprehensive practical training including designing control experiments, executing efficient flash column chromatography, and employing nuclear magnetic resonance (NMR) technology to analyze experimental outcomes. This training equips students with essential skills for modern synthesis techniques and addresses the educational gap in advanced drug synthesis methods and organic chemistry techniques, thereby laying a solid foundation for future academic or professional pursuits.