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

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

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Triftosylhydrazone in Single-Atom Skeletal Editing

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 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.

Language: Английский

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Dimethoxyacetaldehyde-N-triftosylhydrazone: Preparation and Carbene Reactivity in Cyclopropanation and Doyle–Kirmse Reactions

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Herein, we developed the new, powerful, and easy-to-handle chemical reagent, dimethoxyacetaldehyde-N-triftosylhydrazone (DMHz-Tfs), as a convenient in situ source of dimethoxydiazoethane under mild conditions. We demonstrate carbene reactivity DMHz-Tfs iron-catalyzed cyclopropanation Doyle-Kirmse reactions, providing access to diverse acetal functionalized cyclopropanes homoallylic- allenyl-sulfides at gram-scale with high stereoselectivity. DFT calculations elucidated involvement most stable doublet spin state iron-carbene intermediate over other possible states.

Language: Английский

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

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 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.

Language: Английский

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Copper‐Catalyzed Cyclopropenation of Alkynes with Difluoromethyl Carbene^†

Chinese Journal of Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 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.

Language: Английский

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Catalytic Generation of o-Quinone Dimethides by a Nondiazo Approach via Donor/Donor Platinum Carbenes

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 27, 2025

A platinum-catalyzed reaction of enynones with various dienophiles has been developed for the construction tetrahydronaphthalene derivatives, which undergo a Diels-Alder process platinum carbenes and o-quinone dimethide (o-QDM) intermediates. In this protocol, an alkoxy-substituted conjugated enynone is used as nondiazo carbene precursor generation o-QDMs, thereby extending methods available o-QDMs. The characterized by its high atom economy, diastereoselectivity, broad substrate scope.

Language: Английский

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(E)-4,2′,4′-Trimethoxychalcone (Z)-N-Tosyl Hydrazone

Molbank, Journal Year: 2025, Volume and Issue: 2025(2), P. M1997 - M1997

Published: April 27, 2025

The synthesis and structural characterization of (E)-4,2′,4′-trimethoxychalcone (Z)-N-tosyl hydrazone, a conjugated tosylhydrazone derivative, is described. compound was obtained via the condensation (E)-1-(2,4-dimethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one with p-toluenesulfonylhydrazide in methanol under mild conditions, yielding yellow solid 66% yield. structure product confirmed through 1H NMR, 13C IR spectroscopy, mass spectrometry, single-crystal X-ray diffraction analysis, which revealed non-planar molecular conformation Z configuration for C=N double bond. This work part our ongoing research on carbene-mediated transformations.

Language: Английский

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Enantioselective Synthesis of Axially Chiral Alkylidenecyclobutanes via Palladium-Catalyzed N-Tosylhydrazone-Based Carbene Coupling

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: May 11, 2025

The synthesis of axially chiral alkylidenecyclobutanes remains challenging due to the requirement both an efficient asymmetric catalytic system and preservation its inherent strained ring structure. We herein disclose enantioselective carbene cross-coupling reaction cyclobutanecarbaldehyde-derived N-tosylhydrazones with aryl bromides, enabled by palladium catalysis in combination elaborately modified sulfinamide phosphine ligand (Sadphos). This method demonstrates feasibility constructing axial chirality on a metal intermediate precisely through sequential process enantiodetermined migratory insertion followed central-to-axial-chirality-transfer β-H elimination. provides access diverse featuring heteroatom-substituted, tertiary all-carbon quaternary stereocenter excellent yields (up 95%) high enantioselectivities 95% ee). Moreover, enantiomers can be selectively obtained choosing either cis- or trans-cyclobutane substrates stereospecific manner.

Language: Английский

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