Dibenzothiophenium Salts: Practical Alternatives to Hypervalent I(III)-Based Reagents

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

Published: Feb. 2, 2025

ConspectusDuring the past few years, interest among organic synthesis practitioners in use of sulfonium salts has exponentially growth. This can arguably be attributed to a series specific factors: (a) The recent development more direct and efficient protocols for these species, which make reagents wide structural variety easily available multigram scale. (b) recognition that reactivity resembles hypervalent iodine compounds, therefore, they used as effective replacement such species most their applications. (c) Their intrinsic thermal stability tolerance air moisture, clearly surpass I(III)-reagents analogue reactivity, facilitate purification, isolation well-defined storage, safely handling on larger (d) Finally, possibility further functionalize once sulfur-containing platform been incorporated. Specifically, this last synthetic approach is not trivial when working with I(III)-species facilitates access no counterpart I(III) realm.This renewed led improvement already existing transformations well discovery unprecedented ones; particular, by incorporate partners traditional cross-coupling C–H activation steps or combine them modern technologies photocatalysis electrosynthesis. In Account, originally prepared our laboratory will outlined compared I(III)-counterparts. Some are now commercially available, started spread widely across chemistry community, helping speed process identification potentially bioactive products new functionaliced materials. However, challenges still remain. characterized an optimal balance between site-selectivity, showing broader compatibility toward sensitive functional groups need. addition, often makes necessary (sophisticated) catalysts activate latent hidden structures. Although priori one see fact disadvantage, it might actually decisive harvest full potential because surely preparation operational context I(III)-chemistry. If becomes true, may contribute expediting retrosynthetic disconnections that, date, impossible.

Language: Английский

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Skeletal Editing through Cycloaddition and Subsequent Cycloreversion Reactions

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

Published: Jan. 28, 2025

ConspectusSkeletal editing, which involves adding, deleting, or substituting single multiple atoms within ring systems, has emerged as a transformative approach in modern synthetic chemistry. This innovative strategy addresses the ever-present demand for developing new drugs and advanced materials by enabling precise modifications of molecular frameworks without disrupting essential functional complexities. Ideally performed at late stages synthesis, skeletal editing minimizes need cost- labor-intensive processes often associated with de novo thus accelerating discovery optimization complex architectures. While current efforts predominantly focus on monatomic-scale modifications, molecules through cycloaddition followed cycloreversion offers unique to manipulate double-atomic scale. introduces possibilities chemical transformations enables such double-atom transmutation, formal single-atom atom insertion. Early examples relied inherent high reactivity substrates, needed be sufficiently active undergo possess good leaving groups subsequent fragmentation (cycloreversion) step. Recently, however, structural relatively inert substrates become achievable substrate activation strategies designed enhance either step.Along these lines, we recently developed dearomative process activating pyridines. In simple high-yielding operation, oxazinopyridines are readily obtained activated dearomatized isolable intermediates. method enabled us achieve transformation pyridines into benzenes naphthalenes cycloaddition/cycloreversion sequence. this Account, related recent contributions from other research highlighted well, alongside early involving tetrazines, triazines, diazines, similar heterocycles reaction partners. By offering streamlined route modify structures, approaches have demonstrated their ability interconvert arenes heteroarenes shown significant potential late-stage applications well advancing drug synthesis bioactive molecules.In future, will undoubtedly see broader development field editing. New should devised enable not only incorporation nitrogen heteroatoms rings─rather than deletion─but also contraction expand application non-aromatic rings. We hope that advancements summarized Account inspire chemists explore methodologies. pushing boundaries approaches, researchers can unlock opportunities constructing modifying frameworks, eventually paving way chemistry, biology, science.

Language: Английский

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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

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Unimolecular Fragment Coupling and Single Carbon Atom Doping as Tools for Structural Reprogramming

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

Published: March 13, 2025

ConspectusOver the past decade, precise deletion or insertion of atom(s) within a molecular skeleton has emerged as powerful strategy for constructing and diversifying complex molecules. This approach is particularly valuable in organic synthesis, where subtle structural changes can dramatically impact reactivity, stability, function, making it highly relevant to medicinal chemistry material science.Our research focuses on two key reprogramming concepts: unimolecular fragment coupling (UFC) single carbon atom doping (SCAD). These innovative strategies enable efficient modifications that go beyond conventional functional group interconversions reactions, offering new synthetic opportunities chemists.UFC involves selective elimination from skeleton, followed by recombination remaining fragments form bonds. A advantage this intramolecular process its superior chemoselectivity stereoselectivity compared traditional intermolecular reactions. prime example our nickel(0)/N-heterocyclic carbene (NHC)-mediated decarbonylation simple diaryl ketones, yielding biaryls via C–C bond activation. offers an alternative cross-coupling reactions leveraging intrinsic connectivity substrate, enabling more direct atom-economical transformations. We extended concept catalytic amides acylsilanes, further broadening scope UFC include diverse carbonyl-containing precursors.Expanding this, we developed decarboxylative aryl carbamates, nickel(0) catalyst supported polystyrene-anchored bisphosphine ligand facilitates oxidative addition C(aryl)–O extrusion CO2. method provides practical sustainable route while generating CO2 byproduct. Inspired decarboxylation reaction, explored deisocyanative UFC, late-stage removal amide functionalities. allows serve transient directing protecting groups, significantly enhancing utility versatility UFC-based strategies.On other hand, SCAD atomic into without loss leading dramatic changes. successfully applied α,β-unsaturated using NHC one-carbon unit. Remarkably, transformation forms four bonds at center one step, lactams acyclic precursors. skeletal modification unlocks pathways cyclic frameworks with minimal steps.Together, introduce paradigm editing, providing tools rapid controlled framework modifications. By reprogramming, these methodologies expand toolbox chemists, accelerating molecule synthesis streamlining access novel architectures. Account highlights contributions field, demonstrating their potential drive both fundamental discoveries applications chemical synthesis.

Language: Английский

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