Transition Metal-Catalyzed Nitrogen Atom Insertion into Carbocycles

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

ConspectusN-Heterocycles are essential in pharmaceutical engineering, materials science, and synthetic chemistry. Recently, skeletal editing, which involves making specific point changes to the core of a molecule through single-atom insertion, deletion, or transmutation, has gained attention for its potential modify complex substrates. In this context, insertion nitrogen atoms into carbocycles form N-heterocycles emerged as significant research focus modern chemistry owing novel logic. This distinctive retrosynthetic approach enables late-stage modification molecular skeletons provides different pathway synthesizing multiply substituted N-heterocycles. Nevertheless, atom proven challenging because inherent inertness carbon-based difficulty cleaving C-C bonds. Therefore, selective editing remains growing field Account primarily highlights contributions our laboratory active acknowledges key from other researchers. It is organized two sections based on type carbocycle. The first section explores cycloalkenes. Recent Co-catalyzed oxidative azidation strategies have enabled cyclobutenes, cyclopentenes, cyclohexenes, facilitating synthesis polysubstituted pyridines, been conventionally pyridine cross-coupling. subsequent discovery realm arenes. site-selective stable arenes We developed method intramolecular benzene rings 2-amino biaryls by suppressing competing C-H process using paddlewheel dirhodium catalyst. addition, address issues we employed arenols substrates, could act controlling elements editing. reported Cu-catalyzed arenols, proceeds dearomative azidation/aryl migration process, enabling incorporation Inspired result, recently extended reaction model Fe-catalyst facilitate ring contraction nitrogen-inserted product, achieving carbon-to-nitrogen transmutation arenols. Various polyaromatic effectively undergo desired atom's presenting considerable various applications Account, present an overview achievements reactions, with scopes, mechanistic features, applications. anticipate that will provide valuable insights propel development innovative methodologies both N-heterocycle synthesis.

Language: Английский

Aromatic Metamorphosis: Skeletal Editing of Aromatic Rings

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

ConspectusAromatic rings are fundamental structural motifs found in natural products, synthetic intermediates, pharmaceuticals, agrochemicals, and functional materials. While transformations at the periphery of these well-established, modifying their core frameworks has remained an underexplored frontier. Our group pioneered concept, termed "aromatic metamorphosis", enabling skeletal aromatic by replacing endocyclic atom with a different or inserting into rings, which leads to novel strategies diverse molecular architectures.The concept metamorphosis was first demonstrated stepwise conversion dibenzothiophenes dibenzofurans triphenylenes. These transformations, facilitated palladium nickel catalysts, involve strategic activation robust C-S C-O bonds as key steps. Next, approach extended two-step conversions carbazoles, dibenzophospholes, fluorenes, etc., oxidation corresponding sulfones subsequent sequential inter- intramolecular nucleophilic substitution reactions. new routes have provided efficient access optoelectronic Especially, SNAr-based construction heterohelicene library systematic variation atoms. This strategy revolutionized way libraries constructed enables rapid discovery molecules.In addition substitutions, ring-expanding through insertion also been explored. We developed nickel-catalyzed boron benzofurans, generating benzoxaborins, important scaffolds for medicinal chemistry. catalytic transformation successfully scaled industrial synthesis companies, demonstrates practical utility metamorphosis. Furthermore, manganese-catalyzed lithium-metal-promoted methodologies expanded ranges heteroatoms inserted cleaved, providing methods heterocycles diversity element compositions.Reductive dilithiation thiophenes efficiently yields 1,4-dilithiobutadienes, react variety electrophiles produce series nonbiogenic heteroles, such boroles, phospholes, siloles. In principle, this method should allow sulfur readily available be replaced any is therefore considered ideal example terms chemical spaces elements.Aromatic proposes many synthons retrosynthetic disconnections that defy conventional wisdom organic synthesis. By making full use metamorphosing skeleton, can directly minimal effort time investment. Its applications span from pharmaceuticals materials science, paving paradigm design well strategy.

Language: Английский