Carbon–Carbon Bond Cleavage for Late-Stage Functionalization

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(22), P. 12313 - 12370

Published: Nov. 9, 2023

Late-stage functionalization (LSF) introduces functional group or structural modification at the final stage of synthesis natural products, drugs, and complex compounds. It is anticipated that late-stage would improve drug discovery's effectiveness efficiency hasten creation various chemical libraries. Consequently, products a productive technique to produce product derivatives, which significantly impacts biology development. Carbon-carbon bonds make up fundamental framework organic molecules. Compared with carbon-carbon bond construction, activation can directly enable molecular editing (deletion, insertion, atoms groups atoms) provide more efficient accurate synthetic strategy. However, selective unstrained still one most challenging projects in synthesis. This review encompasses strategies employed recent years for cleavage by explicitly focusing on their applicability functionalization. expands current discourse reactions providing comprehensive overview types bonds. includes C-C(sp), C-C(sp2), C-C(sp3) single bonds; double triple bonds, focus catalysis transition metals organocatalysts. Additionally, specific topics, such as ring-opening processes involving three-, four-, five-, six-membered rings, are discussed, exemplar applications these techniques showcased context bioactive molecules discovery. aims shed light advancements field propose potential avenues future research realm

Language: Английский

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Carbonyl umpolung as an organometallic reagent surrogate

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(19), P. 10733 - 10742

Published: Jan. 1, 2021

Carbonyls can serve as surrogates for organometallic reagents via hydrazones.

Language: Английский

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Catalytic Generation of Carbanions through Carbonyl Umpolung

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(40), P. 21624 - 21634

Published: May 15, 2021

Abstract Carbonyl Umpolung is a powerful strategy in organic chemistry to construct complex molecules. Over the last few years, versatile catalytic approaches for generation of acyl anion equivalents from carbonyl compounds have been developed, but methods obtain alkyl carbanions fashion are still at an early stage. This Minireview summarizes recent progress through Umpolung. Two different can be utilized enable compounds: Wolff–Kishner reaction and single‐electron reduction imines. We discuss scope, mechanistic insights, synthetic applications as well potential future developments.

Language: Английский

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Deoxygenative Functionalizations of Aldehydes, Ketones and Carboxylic Acids

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(10)

Published: Nov. 15, 2021

The simple and efficient conversion of carbonyl compounds into functionalized alkanes via deoxygenation is highly enabling in chemical synthesis. This Review covers the recent methodology development carboxyl deoxygenative functionalizations, highlighting some representative significant contributions this field. These advances are categorized based on reactivity patterns oxygenated feedstock compounds, including aldehydes, ketones carboxylic acids. Four types reactive intermediates arising from aldehydes during deoxygenation, namely, bis-electrophiles, carbenoids, bis-nucleophiles alkyl radical equivalents, presented, while acids mainly behave as tris-electrophiles when deoxygenated. In each subcategory, selected examples organized according to type bond formation discussed a generalized mechanistic perspective.

Language: Английский

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Stereoselective gem-Difluorovinylation of gem-Difluorinated Cyclopropanes Enabled by Ni/Pd Cooperative Catalysis

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(19), P. 11960 - 11965

Published: Sept. 13, 2021

A cross-electrophile coupling between gem-difluorinated cyclopropanes and 2,2-difluorovinyl tosylate via dual Ni/Pd cooperative catalysis under mild reaction conditions is presented. Various structurally unique organofluorine compounds bearing both monofluoroalkene gem-difluoroalkene moieties can be effectively afforded in good yields with a high (Z)-selectivity. The synthetic utility of this protocol has been successfully demonstrated by the late-stage modification series complex bioactive molecules.

Language: Английский

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Palladium-Catalyzed C–H Allylation of Electron-Deficient Polyfluoroarenes with gem-Difluorinated Cyclopropanes

Organic Letters, Journal Year: 2021, Volume and Issue: 23(12), P. 4920 - 4924

Published: June 4, 2021

A palladium-catalyzed C-H allylation of electron-deficient polyfluoroarenes with gem-difluorinated cyclopropanes is reported. It provides a useful and facile approach to 2-fluoroallylic in moderate excellent yields high Z-selectivity. In addition, this new has good functional group compatibility broad substrate scope.

Language: Английский

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Transition-Metal-Free, Site-Selective C–F Arylation of Polyfluoroarenes via Electrophotocatalysis

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(37), P. 17261 - 17268

Published: Sept. 7, 2022

Direct CAr-F arylation is effective and sustainable for synthesis of polyfluorobiaryls with different degrees fluorination, which are important motifs in medical material chemistry. However, no aid transition metals, the engagement bond activation has proved difficult. Herein, an unprecedented transition-metal-free strategy reported site-selective polyfluoroarenes simple (het)arenes. By merging N,N-bis(2,6-diisopropylphenyl)perylene-3,4,9,10-bis(dicarboximide)-catalyzed electrophotocatalytic reduction anodic nitroxyl radical oxidation cell, various polyfluoroaromatics (2F-6F 8F), especially inactive partially fluorinated aromatics, undergo sacrificial-reagents-free C-F high regioselectivity, yields comparable to those transition-metal catalysis. This atom- step-economic protocol features a paired electrocatalysis organic mediators both cathodic processes. The broad substrate scope good functional-group compatibility highlight merits this operationally strategy. Moreover, easy gram-scale late-stage functionalization collectively advocate practical value, would promote vigorous development fluorine

Language: Английский

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Palladium-Catalyzed Synthesis of Functionalized Indoles by Acylation/Allylation of 2-Alkynylanilines with Three-Membered Rings

Organic Letters, Journal Year: 2022, Volume and Issue: 24(11), P. 2093 - 2098

Published: March 11, 2022

Palladium-catalyzed synthesis of 3-acyl and -allyl indoles has been realized by merging nucleophilic cyclization ortho-alkynylanilines with ring opening three-membered rings such as cyclopropenones gem-difluorinated cyclopropanes. These functionalized were obtained in moderate to high yields stereoselectivity both cases. This protocol provides an alternative method toward under mild redox-neutral conditions.

Language: Английский

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Pd/NHC-Controlled Regiodivergent Defluorinative Allylation of gem-Difluorocyclopropanes with Allylboronates

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(11), P. 6495 - 6505

Published: May 17, 2022

Controlling the selectivity of synthetically useful reactions has been a longstanding objective organic chemistry. We report regiodivergent synthetic protocol allowing access to diverse fluorinated 1,5-dienes through Pd/NHC-catalyzed ring-opening allylation gem-difluorocyclopropanes. Density functional theory (DFT) calculations on regioselectivity-determining transition states provided critical insight into design NHC ligand for switching regioselectivity. Consistent with DFT predictions, N-heterocyclic carbene (NHC) ligands bulky ortho substituents favored branched allylation, IHept providing > 20:1 branched/linear less hindered such as IMes thermodynamically more stable linear products. were able carry out late-stage modification various complex molecules using this protocol. Our ligand-controlled approach provides efficient regioisomeric from same starting materials and constitutes valuable addition toolbox diversity-oriented synthesis.

Language: Английский

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Site-Divergent Alkenyl C–H Fluoroallylation of Olefins Enabled by Tunable Rhodium Catalysis

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(15), P. 8857 - 8867

Published: July 10, 2022

The unique properties of the fluorine-containing compounds and their widespread applications raise demand for dependable synthetic methods on precise introduction substituents into organic molecules. Herein, a site-divergent fluoroallylation olefins that can incorporate fluoroallyl motif different alkenyl C–H sites is disclosed. gem-Difluorinated cyclopropanes are employed as sources via rhodium-catalyzed C–C bond activation. This strategy provide two regioisomeric fluorinated skipped dienes in good yields with excellent site-selectivity. resulting products serve useful building blocks to access various molecules isosteric β, γ-unsaturated amides, which promising be exploited medicinal chemistry. Mechanistic studies revealed electronic property rhodium catalysts crucial controllable site-selectivity, providing more insights beyond methodology tuning selectivity metal catalysts.

Language: Английский

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