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1. Four‐Selective Pyridine Alkylation via Wittig Olefination of Dearomatized Pyridylphosphonium Ylides

   https://doi.org/10.1002/anie.202109271  

   Fricke, Patrick_J; Dolewski, Ryan_D; McNally, Andrew (August 2021, Angewandte Chemie International Edition)

   Abstract Methods to synthesize alkylated pyridines are valuable because these structures are prevalent in pharmaceuticals and agrochemicals. We have developed a distinct approach to construct 4‐alkylpyridines using dearomatized pyridylphosphonium ylide intermediates in a Wittig olefination‐rearomatization sequence. PyridineN‐activation is key to this strategy, andN‐triazinylpyridinium salts enable coupling between a wide variety of substituted pyridines and aldehydes. The alkylation protocol is viable for late‐stage functionalization, including methylation of pyridine‐containing drugs. This approach represents an alternative to metal‐catalyzedsp²‐sp³cross‐coupling reactions and Minisci‐type processes. 

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2. Pyridylphosphonium salts as alternatives to cyanopyridines in radical–radical coupling reactions

   https://doi.org/10.1039/D1SC02324A  

   Greenwood, Jacob W.; Boyle, Benjamin T.; McNally, Andrew (August 2021, Chemical Science)

   Radical couplings of cyanopyridine radical anions represent a valuable technology for functionalizing pyridines, which are prevalent throughout pharmaceuticals, agrochemicals, and materials. Installing the cyano group, which facilitates the necessary radical anion formation and stabilization, is challenging and limits the use of this chemistry to simple cyanopyridines. We discovered that pyridylphosphonium salts, installed directly and regioselectively from C–H precursors, are useful alternatives to cyanopyridines in radical–radical coupling reactions, expanding the scope of this reaction manifold to complex pyridines. Methods for both alkylation and amination of pyridines mediated by photoredox catalysis are described. Additionally, we demonstrate late-stage functionalization of pharmaceuticals, highlighting an advantage of pyridylphosphonium salts over cyanopyridines. 

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3. Nickel-catalysed sequential hydrodefluorination of pyridines: mechanistic insights led to the discovery of bench-stable precatalysts

   https://doi.org/10.1039/D5QI01257K  

   Duran_Arroyo, Victor; Nuñez, Roger; Arevalo, Rebeca (July 2025, Inorganic Chemistry Frontiers)

   The nickel(0) complex [Ni(^iPrPN)(COD)] (^iPrPN = 2-[(N-diisopropylphosphino)methylamino]pyridine, COD = 1,5-cyclooctadiene) was an efficient precatalyst for the hydrodefluorination of partially fluorinated pyridines employing pinacolborane (HBPin). 

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4. Halogenation of the 3-position of pyridines through Zincke imine intermediates

   https://doi.org/10.1126/science.add8980  

   Boyle, Benjamin T.; Levy, Jeffrey N.; de Lescure, Louis; Paton, Robert S.; McNally, Andrew (November 2022, Science)

   Opening and reclosing pyridines enables selective halogenation at the 3-position of the ring. 

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5. Photoenzymatic Hydrogenation of Heteroaromatic Olefins Using ‘Ene’‐Reductases with Photoredox Catalysts

   https://doi.org/10.1002/anie.202003125  

   Nakano, Yuji; Black, Michael J.; Meichan, Andrew J.; Sandoval, Braddock A.; Chung, Megan M.; Biegasiewicz, Kyle F.; Zhu, Tianyu; Hyster, Todd K. (April 2020, Angewandte Chemie International Edition)

   Abstract Flavin‐dependent ‘ene’‐reductases (EREDs) are highly selective catalysts for the asymmetric reduction of activated alkenes. This function is, however, limited to enones, enoates, and nitroalkenes using the native hydride transfer mechanism. Here we demonstrate that EREDs can reduce vinyl pyridines when irradiated with visible light in the presence of a photoredox catalyst. Experimental evidence suggests the reaction proceeds via a radical mechanism where the vinyl pyridine is reduced to the corresponding neutral benzylic radical in solution. DFT calculations reveal this radical to be “dynamically stable”, suggesting it is sufficiently long‐lived to diffuse into the enzyme active site for stereoselective hydrogen atom transfer. This reduction mechanism is distinct from the native one, highlighting the opportunity to expand the synthetic capabilities of existing enzyme platforms by exploiting new mechanistic models. 

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