Unconventional Transformations of Difluorocarbene with Amines and Ethers

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(5), P. 592 - 607

Published: Feb. 9, 2023

ConspectusFluorine-containing compounds are extensively involved in various fields originating from intriguing and unique characteristics of fluorine atom; notably, pharmaceuticals, the involvement a atom or fluorine-containing group is chief technique for improving pesticide effect developing new drugs. Difluorocarbene, one most important powerful reagents, widely employed studied many areas mainly to assemble gem-difluoromethyl molecules, including but not limited abundant reactions between difluorocarbene with nucleophilic substrates, Wittig reaction ketones aldehydes, cascade both nucleophile an electrophile, [2+1] cycloaddition alkenes alkynes. However, its unconventional protocols beyond as difluoromethyl synthon have rarely been studied, thus, it highly desired given abundance, inexpensiveness peculiar properties. In this Account, we discuss our discovery transformations difluorocarbene, instead sole source (different other dihalocarbene), actually can serve electron acceptor activate C-X bonds (X = N O) thus promote myriad fascinating assembly versatile valuable products aza-compounds (primary/secondary/tertiary amines well NH3 NaNH2 so on) aliphatic ethers absence transition metals expensive ligands. Inspired by electron-deficient first found that isocyanides could be readily formed situ when unoccupied orbital meets lone-pair primary amines; basic condition, defluorination cyclizations afford plethora N-containing heterocycles. Meanwhile, disclosed cyano anion accessible were mixed up suitable conditions, series aryl nitrile obtained presence Pd catalysis ArI. Interestingly, encountered secondary amines, formamides rendered under mild reactions. Of note, concomitant functionalizations C moieties via cleavage unstrained C(sp3)-N bond metal oxidant sparce, which indeed significantly add versatility diversity products. Gratifyingly, uitilizing cyclic tertiary achieved difluorocarbene-mediated deconstructive time, showing successive scission simultaneous functionalization atoms would introduced into oxidants. This method provides brand-new while very universal synthetic pathway selectively cleave inert unactivated Csp3-N bonds, halodifluoromethyl reagents act C1 halo (Cl, Br, I) sources. Fascinatingly, nitrogen ylides generated approach deaminative arylation alkenylation was time appropriate represents mode lead formal transition-metal free Suzuki cross coupling. Besides, also proceed novel recombination render meaningful 2-fluoroindoles 3-(2,2-difluoroethyl)-2-fluoroindoles ortho-vinylanilines, 3-fluorined oxindoles 2-aminoarylketones, acts F1 simultaneously. Last least, recently lone-pair-electron oxygen trap form oxonium ylide, eventually leads C-O formation ethers.

Language: Английский

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Palladium-Catalyzed Difluorocarbene Transfer Enabled Divergent Synthesis of γ-Butenolides and Ynones from Iodobenzene and Terminal Alkynes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(2), P. 1722 - 1731

Published: Jan. 4, 2024

Herein, we report a ligand-controlled palladium-catalyzed method that enables the synthesis of ynones and γ-butenolides with excellent regioselectivity from same set readily available aryl iodides, acetylenes, BrCF2CO2K. In this reaction, [PdII]═CF2 does demonstrate electrophilicity can generate CO when reacting H2O. It is environmentally friendly safe compared to traditional methods, current protocol us afford in high yields functionality tolerance. Moreover, esters also be obtained corresponding phenols alcohols utilizing strategy. The success late-stage functionalization bioactive compounds further illustrates synthetic utility material development drug discovery.

Language: Английский

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Unlocking Diverse π-Bond Enrichment Frameworks by the Synthesis and Conversion of Boronated Phenyldiethynylethylenes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(14), P. 10167 - 10176

Published: March 27, 2024

The π-bond enrichment frameworks not only serve as a crucial building block in organic synthesis but also assume pivotal role the fields of materials science, biomedicine, photochemistry, and other related disciplines owing to their distinctive structural characteristics. incorporation various substituents into C═C double bonds tetrasubstituted alkenes is currently highly significant research area. However, with diverse on poses challenge achieving stereoselectivity. Here, we reported an efficient convergent route Cu-catalyzed borylalkynylation both symmetrical unsymmetrical 1,3-diynes, B2pin2, acetylene bromide construction boronated phenyldiethynylethylene (BPDEE) derivatives excellent chemo-, stereo-, regioselectivities. BPDEE could transform novel π-conjugated gem-diphenyldiethynylethylene (DPDEE), vinylphenyldiethynylethylene (VPDEE), phenyltriethynylethylene (PTEE) by stepwise process, which provides flexible platform for complex that were difficult synthesize previous methods. initial optical characterization revealed synthesized molecules exhibited aggregation-induced emission (AIE) properties, further establishes groundwork future applications enriches advances field functional research.

Language: Английский

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Difluorocarbene-induced [1,2]- and [2,3]-Stevens rearrangement of tertiary amines

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 5, 2024

The [1,2]- and [2,3]-Stevens rearrangements are one of the most fascinating chemical bond reorganization strategies in organic chemistry, they have been demonstrated a wide range applications, representing fundamental reaction tactic for synthesis nitrogen compounds community. However, their applicabilities limited by scarcity efficient, general, straightforward methods generating ammonium ylides. Herein, we report general difluorocarbene-induced tertiary amine-involved stemmed from situ generated difluoromethyl ylides, which allows versatile amines bearing either allyl, benzyl, or propargyl groups, resulting corresponding products under same conditions with way. Broad substrate scope, simple operation, mild late-stage modification natural highlight advantages this strategy, meanwhile, rearrangement is believed to bring opportunities transformations ylides assembly valuable amino acids. This will further enrich repertoire difluorocarbene species, facilitate development reactions involving salts, provide an avenue type reactions.

Language: Английский

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Synthesis of 2‐Trifluoromethyl‐4‐aminoquinolines via Heating‐Promoted Multi‐component Reaction of CF₃‐Imidoyl Sulfoxonium Ylides and Amines with Difluorocarbene as a C1 Synthon^†

Chinese Journal of Chemistry, Journal Year: 2023, Volume and Issue: 41(23), P. 3205 - 3210

Published: July 17, 2023

Comprehensive Summary A thermally‐induced multi‐component reaction of CF 3 ‐substituted imidoyl sulfoxonium ylides (TFISYs), amines and (triphenylphosphonio)difluoroacetate (PDFA) has been developed, allowing a facile access to 2‐trifluoromethyl‐4‐aminoquinolines in high yields. The proceeds smoothly with or without the addition sulfur utilizes difluorocarbene as C1 synthon under simply heating conditions. Mechanistic study reveals that in‐situ generated thiocarbonyl fluoride, isothiocyanate gem ‐difluoroalkene might act key intermediates.

Language: Английский

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Assembly of Diverse Allenes via Activator-Free Palladium-Catalyzed Regioselective γ-Arylation of Propargylamines with Boronic Acids

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Controlling the reaction selectivity to achieve a precision synthesis is constant concern for chemists. Here, we report palladium-catalyzed deaminative coupling of propargylamines with arylboronic acids generate allene skeletons. Importantly, this approach allows regioselective γ-arylation unactivated propargyl tertiary amines access various allenes in absence amino-activating reagents. We present wide range and boronic demonstrate synthetic application target products construct valuable compounds.

Language: Английский

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Recent Progress in Selective C—H Chlorination

Chinese Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 45(2), P. 574 - 574

Published: Jan. 1, 2025

Language: Английский

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Difluorocarbene-Enabled Synthesis of 3-Alkenyl-2-oxindoles from ortho-Aminophenylacetylenes

Organic Letters, Journal Year: 2023, Volume and Issue: 25(7), P. 1178 - 1182

Published: Feb. 9, 2023

Herein, we report a transition-metal-free [4 + 1] cyclization pathway from difluorocarbene and ortho-amino aryl alkynone, rendering an effective universal strategy for the construction of 3-alkenyl-2-oxindoles. Our starts cheap accessible alkynone instead direct indole skeleton; moreover, in situ generated commercially available halogenated difluoroalkylative reagents enables cleavage C–N bond formation new bonds C–C bonds.

Language: Английский

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Cooperative Triple Catalysis Enables Deaminative α-Indolmethylation of Carbonyl Compounds with Gramines

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(2), P. 1064 - 1072

Published: Jan. 8, 2024

α-Functionalization of carbonyl compounds is an important reaction in synthetic chemistry. However, the development novel strategies to realize this challenging. This study describes α-indolmethylation using cooperative copper, amine, and hydrogen-bond catalysis. provides a efficient strategy for developing indolmethylated by deaminative coupling gramines.

Language: Английский

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Base-promoted triple cleavage of CCl₂Br: a direct one-pot synthesis of unsymmetrical oxalamide derivatives

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(22), P. 3079 - 3082

Published: Jan. 1, 2024

We present a novel, eco-friendly and one-pot approach for synthesizing unsymmetrical oxalamides with the aid of dichloroacetamide amine/amides in presence CBr

Language: Английский

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