Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...

Herein, we report a practical and efficient carbon-to-nitrogen atom swap in 2-phenylimidazo[2,1-a]isoquinoline and 2-phenylimidazo[1,2-a]quinoline scaffolds, enabling their direct conversion to the corresponding 2-phenyl-[1,2,4]triazolo[5,1-a]isoquinoline and 2-phenyl-[1,2,4]triazolo[1,5-a]quinoline analogues. This transformation exploits the intrinsic reactivity of the parent heterocycles to undergo a cascade sequence involving oxidative cleavage, amination, and cyclization (OCAC) under mild conditions with functional group tolerance.

Oxygen-atom transfer (OAT) reactions, such as epoxidation, often use stoichiometric high-energy oxygen donors that present safety hazards, especially on large scale. Electrochemistry provides a means to replace these reagents with water as the O-atom donor. Here, we identify an electron-deficient Mn-porphyrin electrocatalyst that enables efficient OAT to alkenes and pyridines to access epoxides and N-oxides. The scope of the reaction includes terminal and electron-deficient alkenes that often prove challenging with other chemical and electrochemical methods. Direct comparisons with two chemical oxidation methods, (i) stoichiometric meta-chloroperoxybenzoic acid and (ii) the same Mn-porphyrin catalyst with PhI(OAc)2 as the oxidant, highlight the merits of the electrochemical reaction. Prospects for scalable application of the method is demonstrated through oxidation of pharmaceutically relevant alkenes in a stirred tank electrochemical reactor.

Pairs of heterocycles differing by a single constitutive ring atom can exhibit stark differences in the retrosynthetic disconnections available for their preparation. Such a synthesis gap is exemplifi...

Bioisosteric replacement is vital in drug discovery; however, substituting core ring structures is challenging. Now, a strategy that converts pyridines into benzonitriles, via N-oxidation, photochemic...

Direct regioselective C-3 halogenation of pyridines is achieved using ether solvents, and interactions between the pyridine substrate, ether solvent and haleniums play a dominant role in the reactivit...

O’Hagan, D. Pyrrole, pyrrolidine, pyridine, piperidine and tropane alkaloids. Nat. Prod. Rep. 17, 435–446 (2000). Lamberth, C. Heterocyclic chemistry in crop protection. Pest Manag. Sci. 69, 1106–1114 (2013). Ling, Y. et al. The expanding role of pyridine and dihydropyridine scaffolds...

The asymmetric partial reduction (APR) of substituted pyridines represents a direct and versatile strategy to access chiral dihydropyridines (DHPs) and tetrahydropyridines (THPs), which are present in many natural products and active pharmaceutical ingredients (APIs). However, this methodology remains significantly underdeveloped when compared with the numerous exhaustive asymmetric reductions of pyridines to fully saturated piperidines, and is currently still limited to the synthesis of THPs. In this opinion, we highlight the benefits, challenges, and current scope of asymmetric partial pyridine reductions, emphasizing prospective future directions to address significant gaps in the current literature.