The radical-mediated C-H functionalization of pyridines has attracted considerable attention as a powerful tool in synthetic chemistry for the direct functionalization of the C-H bonds of the pyridine scaffold. Classically, the synthetic methods for functionalized pyridines often involve radical-mediated Minisci-type reactions under strongly acidic conditions. However, the site-selective functionalization of pyridines in unbiased systems has been a long-standing challenge because the pyridine scaffold contains multiple competing reaction sites (C2 vs C4) to intercept free radicals. Therefore, prefunctionalization of the pyridine is required to avoid issues observed with the formation of a mixture of regioisomers and overalkylated side products.Recently, <i>N</i>-functionalized pyridinium salts have been attracting considerable attention in organic chemistry as promising radical precursors and pyridine surrogates. The notable advantage of <i>N</i>-functionalized pyridinium salts lies in their ability to enhance the reactivity and selectivity for synthetically useful reactions under acid-free conditions. This approach enables exquisite regiocontrol for nonclassical Minisci-type reactions at the C2 and C4 positions under mild reaction conditions, which are suitable for the late-stage functionalization of bioactive molecules with greater complexity and diversity. Over the past five years, a variety of fascinating synthetic applications have been developed using various types of pyridinium salts under visible light conditions. In addition, a new platform for alkene difunctionalization using appropriately designed <i>N</i>-substituted pyridinium salts as bifunctional reagents has been reported, offering an innovative assembly process for complex organic architectures. Intriguingly, strategies involving light-absorbing electron donor-acceptor (EDA) complexes between pyridinium salts and suitable electron-rich donors further open up new reactivity under photocatalyst-free conditions. Furthermore, we developed enantioselective reactions using pyridinium salts to afford enantioenriched molecules bearing pyridines through single-electron <i>N</i>-heterocyclic carbene (NHC) catalysis.Herein, we provide a broad overview of our recent contributions to the development of <i>N</i>-functionalized pyridinium salts and summarize the cornerstones of organic reactions that successfully employ these pyridinium salts under visible light conditions. The major advances in the field are systematically categorized on the basis of the pyridines' <i>N</i>-substituent, <i>N</i>-X (X = O, N, C, and SO₂CF₃), and its reactivity patterns. Furthermore, the identification of new activation modes and their mechanistic aspects are discussed by providing representative contributions to each paradigm. We hope that this Account will inspire broad interest in the continued innovation of <i>N</i>-functionalized pyridinium salts in the exploration of new transformations.

Saturated benzene bioisosteres alleviate the constraints of aromatic planarity; however, oxygen-containing variants remain underdeveloped with limited positional diversity. Here we report a visible-light-driven oxygenation of bicyclo[1.1.0]butanes that encodes ring-open-close programmability to construct unique oxygenated bicycles, 5-oxa-2-oxobicyclo[2.1.1]hexanes (5-oxa-2-oxo-BCHex), bearing new exit vectors. Pyridine N-oxides act as oxene surrogates, effecting selective cleavage of the bridge C-C bond to generate β,γ-unsaturated 1,2-diketones that rapidly undergo a photoinduced intramolecular Paternò-Büchi [2 + 2] cycloaddition to reclose the bicycle. Although either carbonyl can engage, a reversible retro-[2 + 2] equilibrium self-corrects off-pathway adducts, funneling reactivity to 5-oxa-2-oxo-BCHexs. Notably, further pathway control enables divergence: Lewis-acid activation furnishes hydroxy-cyclopentenones, whereas sequential phototransformation affords cyclopropane-fused γ-lactones. Uncovering a new BCB reactivity, this programmed ring-open-close logic expands the oxygenated bicyclic chemical space available from a single BCB precursor and enriches the repertoire of site-diversified benzene bioisosteres.

Controlling the site of amination on N-heteroarenes is pivotal for rapid exploration of structure-activity relationships, yet a single-precursor platform that toggles between C3 and C4 amination of quinolines has remained elusive. Here we report a regiodivergent method that channels quinoline amination to C3 or C4 through orthogonal radical and ionic manifolds. Under visible-light, donor-assisted electron-donor-acceptor (EDA) conditions, homolytic N─N cleavage of N-aminoquinolinium salts generates N-centered radicals that selectively install amino groups at C3 via capture by an enamine intermediate (radical pathway) formed through traceless nucleophile-induced dearomatization. In the absence of light and donor, the same quinolinium salt undergoes a two-electron ionic process: S_NAr-type addition of amines at C4, followed by base-promoted rearomatization to furnish C4-aminated products. The method proceeds under mild conditions, accommodates a broad range of quinolines and amine partners, and enables late-stage diversification. Mechanistic experiments support an EDA-initiated origin for the C3 manifold and an ionic mechanism for C4, establishing condition-gated control over quinoline C─N bond formation.

ABSTRACT Controlling the site of amination on N‐heteroarenes is pivotal for rapid exploration of structure–activity relationships, yet a single‐precursor platform that toggles between C3 and C4 amination of quinolines has remained elusive. Here we report a regiodivergent method that channels quinoline amination to C3 or C4 through orthogonal radical and ionic manifolds. Under visible‐light, donor‐assisted electron‐donor–acceptor (EDA) conditions, homolytic N─N cleavage of N‐aminoquinolinium salts generates N‐centered radicals that selectively install amino groups at C3 via capture by an enamine intermediate (radical pathway) formed through traceless nucleophile‐induced dearomatization. In the absence of light and donor, the same quinolinium salt undergoes a two‐electron ionic process: S N Ar‐type addition of amines at C4, followed by base‐promoted rearomatization to furnish C4‐aminated products. The method proceeds under mild conditions, accommodates a broad range of quinolines and amine partners, and enables late‐stage diversification. Mechanistic experiments support an EDA‐initiated origin for the C3 manifold and an ionic mechanism for C4, establishing condition‐gated control over quinoline C─N bond formation.

Abstract Hydrogen atom transfer (HAT) reactions play a vital role in radical chemistry and biological systems, enabling selective C–H functionalization through bond dissociation energy and polarity effects. Whereas intramolecular 1,5-HAT is well established, 1,2-HAT processes remain relatively challenging, particularly for nitrogen-centered radicals, due to high activation barriers. Here, we report a successful 1,2-HAT of amidyl radicals generated from N-amidopyridinium salts, enabled by a frustrated Lewis pair system of t-Bu3P and the pyridinium salt, without requiring an external photocatalyst. The phosphine serves dual roles: reducing the pyridinium salt through single-electron transfer and facilitating the 1,2-HAT process under mild conditions. Visible-light irradiation enhances the reaction efficiency, allowing late-stage functionalization of pyridine-containing pharmaceuticals. This method offers a new approach to selective pyridine C–H functionalization, broadening the scope of HAT chemistry in synthesis.

We consider theories of gauged quark flavor and identify noninvertible Peccei-Quinn symmetries arising from fractional instantons when the resulting gauge group has nontrivial global structure. Such symmetries exist solely because the standard model has the same number of generations as colors, <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" display="inline"><a:msub><a:mi>N</a:mi><a:mi>g</a:mi></a:msub><a:mo>=</a:mo><a:msub><a:mi>N</a:mi><a:mi>c</a:mi></a:msub></a:math>, which leads to a massless down-type quark solution to the strong <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" display="inline"><c:mi>C</c:mi><c:mi>P</c:mi></c:math> problem in an ultraviolet <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" display="inline"><e:mi>S</e:mi><e:mi>U</e:mi><e:mo stretchy="false">(</e:mo><e:mn>9</e:mn><e:mo stretchy="false">)</e:mo></e:math> theory of quark color-flavor unification. We show how the Cabibbo-Kobayashi-Maskawa flavor structure and weak <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" display="inline"><i:mi>C</i:mi><i:mi>P</i:mi></i:math> violation can be generated without upsetting our solution.

Bridged bicyclic scaffolds such as bicyclo[2.1.1]hexanes (BCHs) and bicyclo[3.1.1]heptanes (BCHeps) have emerged as valuable bioisosteres for ortho- and meta-substituted arenes in contemporary drug design. These three-dimensional frameworks offer enhanced conformational rigidity and superior physicochemical properties compared to their planar aromatic counterparts. The precise control of stereochemistry in these scaffolds is paramount, as chirality profoundly influences biological activity and pharmacokinetic profiles. Strain-release transformations of bicyclo[1.1.0]butanes (BCBs) represent particularly efficient and atom-economical synthetic approaches to access these architectures. Despite significant advances in this field, catalytic asymmetric methodologies employing BCBs remain notably underdeveloped. This perspective highlights recent breakthroughs in asymmetric transformations of BCBs, with particular emphasis on innovative stereoselective catalytic strategies. We systematically analyze emerging chiral catalyst systems and unique activation modes that enable precise enantiocontrol in BCB functionalization, highlighting their potential applications in medicinal chemistry.