Dong Wang

A traceless tert -butyl dearomatization strategy enables redox-neutral, transition-metal-free meta -C–H alkylation and alkenylation of pyridines, uncovering a pyridine-specific reactivity profile distinct from quinolines.

The direct functionalization of pyridines is a central challenge in modern synthetic organic chemistry, owing to the poor selectivity and reactivity associated with their low-energy π-system. In contrast to traditional functionalization methods that rely on halogen substitution via SNAr reactions, the C–H bond functionalization of pyridines and related electron-deficient heterocycles represents a transformative strategy in modern organic synthesis, enabling the direct modification of complex molecular frameworks with high efficiency and selectivity. This chapter focuses on the available synthetic methods for the C–H bond functionalization of pyridines using phosphorus-mediated strategies, with particular emphasis on recent advances (post-2021). The reaction scope, mechanisms, and regioselectivity will be comprehensively discussed. For each method, the advantages, limitations, synthetic scope, functional group tolerance, reaction efficiency, catalyst economy, atom economy, and environmental considerations are critically evaluated. The application of these methods to a range of medicinally relevant pyridines will also be included.

This strategy bypasses conventional methods by using readily available 2-substituted quinoline N -oxides and phenols to construct 2,3-disubstituted quinolines via [1,2]-alkyl/alkenyl migration under benign conditions.

We report a transition metal-free, environmentally benign method for direct C4–H amination of quinolines and pyridines. Using a base and activating agent in ethyl acetate, it enables mild, efficient amination of diverse 2-substituted substrates.

Antimicrobial resistance represents a major global public health challenge, with infections caused by multidrug-resistant pathogens such as MRSA being a core difficulty in clinical anti-infective therapy. Traditional fluoroquinolones are severely limited by cross-resistance and inadequate biofilm eradication. The 1,8-naphthyridin-4-one-3-carboxylic acid scaffold is privileged for quinolone antibacterials, and novel benzo[b]naphthyridinone-3-carboxylic acid derivatives offer a key strategy to overcome resistance. Herein, we optimized two complementary synthetic routes for the preparation of benzo[b]naphthyridinone-3-carboxylic acid derivatives, and systematically evaluated their antibacterial activity, safety profiles and mechanism of action using standard microbiological assays and molecular modeling. We synthesized eight 1,8-naphthyridinone derivatives, nine benzo[b]naphthyridinone derivatives and 85 key intermediates, with a shortest 6-step route overcoming the long-standing bottleneck of lengthy synthetic steps for this series. Lead compound 13kb displayed potent broad-spectrum activity (MIC = 0.08–0.63 μg/mL against Staphylococcus aureus, Escherichia coli, MRSA and Shigella flexneri), outperforming positive controls. It showed low cytotoxicity and hemolysis, concentration-dependent bactericidal effects, mature biofilm elimination and efficient DNA gyrase binding. This study provides efficient synthetic methodology and promising drug candidates for novel antibacterial development.

We report a transient directing group strategy for direct assembly of diheteroarylalkanes via regioselective C(sp ² )–H methylenation using Eschenmoser's salt, demonstrating broad substrate scope under mild, redox-neutral conditions.

A solvent‐, transition‐metal‐, and base‐free organocatalytic system (Ph ₃ CBr or TMSI) enables efficient O‐ to N‐migration for N‐alkylated pyridone synthesis. Critically, gram‐scale production of a cinnamyl‐derived product (4.73 mmol) completes within 3 h at 100°C without yield erosion. Stereospecific [1,3]‐rearrangements predominantly preserve alkene geometry, while resultant pyridones exhibit tunable fluorescence (Φ up to 0.39 in chloroform). This protocol establishes an eco‐compatible, directly amplifiable platform toward functional heterocycles.

The introduction of cyano groups into aza-heterocyclic compounds plays a pivotal role in accessing diverse derivatives that are essential for the development of natural products, pharmaceuticals, and agrochemicals. Herein, we report a unified strategy for the direct ortho-C-H cyanation of a broad range of heterocyclic N-oxides, including pyridine, quinoline, isoquinoline, and pyrimidine derivatives. This transformation proceeds under mild conditions without the need for external activating agents or catalysts, and has been successfully applied to structurally complex, biologically relevant molecules. Compared to existing methodologies, our approach offers several distinct advantages: the use of non-prefunctionalized heteroarene substrates, environmentally benign reaction solvents, operational simplicity, broad substrate scope, and high efficiency in generating diverse ortho-cyanated heterocyclic compounds. Moreover, the method demonstrates considerable potential for scalable synthesis.

Acetone, a key biomarker for metabolic processes, and its excessive levels can cause ketosis or even ketoacidosis, posing significant risks to human health. Therefore, real-time acetone detection is crucial for noninvasive health monitoring. Ti₃C₂T_x-based sensors demonstrated considerable potential for detecting VOC gases but often face issues with sensitivity and environmental stability. In this work, a flower-like Ti₃C₂T_x anchored with MoS₂ quantum dots (F-Ti₃C₂T_x/MoS₂) was proposed for the first time to achieve accurate acetone detection even under high humidity conditions. The unique flower-like morphology significantly increased the surface area of Ti₃C₂T_x and amplified its electron scattering effects. MoS₂ modification not only reduced the content of Ti defects but also formed a passivation layer, providing a novel approach to address the inherent oxidation issue of Ti₃C₂T_x. Moreover, the p-n heterojunction between F-Ti₃C₂T_x and MoS₂ promoted charge separation, enabling high-performance acetone detection. Compared with intrinsic Ti₃C₂T_x, a 4.83-fold enhancement in response to 25 ppm of acetone was achieved by using a F-Ti₃C₂T_x/MoS₂ sensor with an ultralow detection limit of 163.2 ppb and a rapid response/recovery time (26.0 s/33.7 s). When integrated into a portable breath analyzer, the sensor demonstrated accurate acetone monitoring under atmospheric conditions, underscoring its potential for real-time and noninvasive health diagnostics.