The Carbene Chemistry of N-Sulfonyl Hydrazones: The Past, Present, and Future

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

N-Sulfonyl hydrazones have been extensively used as operationally safe carbene precursors in modern organic synthesis due to their ready availability, facile functionalization, and environmental benignity. Over the past two decades, there has tremendous progress chemistry of N-sulfonyl presence transition metal catalysts, under metal-free conditions, or using photocatalysts photoirradiation conditions. Many transfer reactions are unique cannot be achieved by any alternative methods. The discovery novel development highly enantioselective new skeletal editing represent notable recent achievements hydrazones. This review describes overall made hydrazones, organized based on reaction types, spotlighting current state-of-the-art remaining challenges addressed future. Special emphasis is devoted identifying, describing, comparing scope limitations methodologies, key mechanistic scenarios, potential applications complex molecules.

Язык: Английский

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Triftosylhydrazone in Single-Atom Skeletal Editing

Accounts of Chemical Research, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

ConspectusIn the past decade, single-atom skeletal editing, which involves precise insertion, deletion, or exchange of single atoms in core skeleton a molecule, has emerged as promising synthetic strategy for rapid construction diversification complex molecules without laborious de novo processes. Among them, carbene-initiated editing is particularly appealing due to ready availability and diverse reactivities carbene species. The initial endeavors modify heteroarenes through carbon-atom insertion could date back 1881, when Ciamician Denstedt described conversion pyrroles pyridines by trapping haloform-derived free carbene. Despite its potential value, general applicability this one-carbon seen limited progress poor yields harsh reaction conditions. Significant advances via were achieved only 3 years Levin, Ball, Xu, Song, Glorius, others. hallmark these approaches facile halocyclopropanation followed regioselective ring opening facilitated expulsion halide ion. Consequently, specially designed α-halocarbene precursors, such haloform derivatives, α-halodiazoacetates, chlorodiazirines, α-chlorodiazo oxime esters, can be employed achieve Ciamician–Denstedt-type editing. This not limits types functional groups installed on expansion products but also prevents their widespread adoption, especially late-stage contexts. enduring quest develop environmentally friendly versatile superior group compatibility, application diversifications investigation mechanistic insights into carbon reactions remain fundamental objective.In our over 5 years, we have developed o-trifluoromethylbenzenesulfonylhydrazones (named Triftosylhydrazones) operationally safe easily decomposable diazo surrogates explored various challenging catalytic transfer reactions. Recently, put great efforts expanding scope unlocking triftosylhydrazones precursors Since 2018, realized range acyclic 1,3-dicarbonyls with silver carbenes access 1,4-dicarbonyls, proceeding cyclopropanation/ring-opening process. Inspired results, recently demonstrated series transition-metal-catalyzed highly selective medicinally interesting like pyrroles, indoles, 1,2-diazoles carbenic insertion. We then strained three-membered nitrogen- oxygen-containing heterocycles single-carbon atoms. In Account, present an overview achievements heterocycles, organized based three situ-generated key intermediates, cyclopropane, N-ylide, O-ylide from focus scopes, features, applications. hope that Account will provide valuable contribute development new methodologies both chemistry fields.

Язык: Английский

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Halogencarbene-free Ciamician-Dennstedt single-atom skeletal editing

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 19, 2024

Single-atom skeletal editing is an increasingly powerful tool for scaffold hopping-based drug discovery. However, the insertion of a functionalized carbon atom into heteroarenes remains rare, especially when performed in complex chemical settings. Despite more than century research, Ciamician-Dennstedt (C-D) rearrangement limited to halocarbene precursors. Herein, we report general methodology reaction using α-halogen-free carbenes generated situ from N-triftosylhydrazones. This one-pot, two-step protocol enables various carbenes, including those previously unexplored C-D chemistry, indoles/pyrroles scaffolds access 3-functionalized quinolines/pyridines. Mechanistic studies reveal pathway involving intermediacy 1,4-dihydroquinoline intermediate, which could undergo oxidative aromatization or defluorinative form different carbon-atom products. Ciamician–Dennstedt authors

Язык: Английский

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Multi-Aryl Pyrroles: Exploring Aggregation-Induced Emission for the Biological/Medical Applications

Dyes and Pigments, Год журнала: 2025, Номер unknown, С. 112633 - 112633

Опубликована: Янв. 1, 2025

Язык: Английский

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Controllable Molecular Editing of 2-Amino-N-substituted Benzamides: Site-selective Synthesis of 6-Selenylated N-Substituted 1,2,3-Benzotriazine-4(3H)-ones

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

We present an efficient silver-catalyzed one-pot controllable molecular editing protocol for the transformation of 2-amino-N-substituted benzamides into 6-selenylated N-substituted 1,2,3-benzotriazine-4(3H)-ones under mild reaction conditions. This three-component strategy is achieved by building N-N/N═N/C-Se bonds, which provides a practical pathway preparation selenylated with broad substrate scope and good functional group tolerance, as well high site-selectivity. Mechanistic experiments suggest that this proceeds via intermolecular site-selective C-H selenylation readily available diselenides, followed annulation using AgNO3 nitrogen synthon.

Язык: Английский

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Copper-Catalyzed Cross-Coupling of Bicyclobutanes with Triftosylhydrazone Leading to Skipped Dienes

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Here, we report a protocol for the synthesis of skipped dienes through cross-coupling bicyclo[1.1.0]butanes with trifluoromethyl triftosylhydrazones. The reaction is run using TpBr3Cu(NCMe) as catalyst to give access library trifluoromethylated (32 examples, ≤98% yield) excellent E/Z selectivity under mild and operationally safe conditions. presented methods proved be compatible various functionalized

Язык: Английский

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Pyrrolidine synthesis via ring contraction of pyridines

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 13, 2025

A ring contraction of easily available cyclic compounds to smaller cycles that are valuable but difficult synthetically access is one important skeletal editing strategies. Pyrrolidine synthesis via a pyridines, which abundant, cheap, and readily bulk chemicals in chemical industry, highly promising accelerate drug discovery development research due the great demand pyrrolidine skeletons medicinal molecules. Herein we report photo-promoted pyridines with silylborane afford derivatives bearing 2-azabicyclo[3.1.0]hex-3-ene skeleton. The reaction demonstrates broad substrate scope high functional group compatibility, realizing facile 6-silyl-2-azabicyclo[3.1.0]hex-3-ene work as powerful synthons for functionalized pyrrolidines nitrogen-containing compounds. mechanism clarified proceed 2-silyl-1,2-dihydropyridine vinylazomethine ylide intermediates, connected photochemical or thermal silyl migration. Ring an strategy. Here, authors 2- azabicyclo[3.1.0]hex-3-ene

Язык: Английский

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Silver-Catalyzed Doyle–Kirmse Reaction of Allyl Sulfides with Vinyl Triftosylhydrazones

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

Here, we report a general and practical Doyle-Kirmse reaction of allyl/propargyl sulfides with donor-only vinyl carbenes generated in situ from triftosylhydrazones the presence silver catalyst. This protocol features mild conditions, exhibits broad substrate scope exceptional functional group tolerance, provides corresponding 1,5-dienyl 1,4-enallenyl high yields. Moreover, gram-scale synthesis, late-stage modifications complex molecules, post-synthetic transformations were performed to demonstrate applicability this protocol.

Язык: Английский

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Copper‐Catalyzed Cyclopropenation of Alkynes with Difluoromethyl Carbene^†

Chinese Journal of Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Comprehensive Summary The [2+1] cycloaddition of alkynes with fluoroalkyl carbenes represents the most straightforward approach for constructing fluoroalkylated cyclopropenes. However, until now, this strategy has not been applicable to difluoromethyl carbene, as its precursor, diazomethane, tends undergo [3+2] form pyrazoles. This study presents first example copper‐catalyzed cyclopropenation employing difluoroacetaldehyde triftosylhydrazone carbene precursor. A wide range internal and terminal alkynes, featuring diverse functional groups, were efficiently converted into corresponding cyclopropenes in good high yields. Mechanistic investigations, supported by DFT calculations, revealed that bulky Tp Br3 Cu(NCMe) catalyst plays a pivotal role facilitating via concerted pathway.

Язык: Английский

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Modern Dearomative Enlargement of Heteroaromatic Rings

Synthesis, Год журнала: 2024, Номер 56(20), С. 3119 - 3130

Опубликована: Май 29, 2024

Abstract Breaking aromaticity by inserting additional atoms within the skeleton of heteroaromatic rings has gained significant attention over years. As part emerging concept ‘skeletal editing’, this short review retraces recent progress made on dearomative enlargement reactions both five- and six-membered heterocycles. 1 Introduction 2 Dearomative Enlargement Five-Membered Rings 2.1 Pyrroles, Furans, Thiophenes Their Fused Analogues 2.2 Pyrazoles, Isoxazoles, Isothiazoles 3 Six-Membered 4 Conclusion Perspectives

Язык: Английский

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