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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Rhodium Catalyzed Regioselective C−H Allylation of Simple Arenes via C−C Bond Activation of Gem‐difluorinated Cyclopropanes

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(19), P. 10626 - 10631

Published: Feb. 18, 2021

Herein, we report a rhodium catalyzed directing-group free regioselective C-H allylation of simple arenes. Readily available gem-difluorinated cyclopropanes can be employed as highly reactive allyl surrogates via sequence C-C and C-F bond activation, providing arene derivatives in good yields with high regioselectivity under mild conditions. The robust methodology enables facile late-stage functionalization complex bioactive molecules. efficiency this reaction is also demonstrated by the turnover number (TON, up to 1700) catalyst on gram-scale experiments. Preliminary success kinetic resolution transformation achieved, promising access enantio-enriched cyclopropanes.

Language: Английский

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Cu/Pd-Catalyzed cis-Borylfluoroallylation of Alkynes for the Synthesis of Boryl-Substituted Monofluoroalkenes

Organic Letters, Journal Year: 2021, Volume and Issue: 23(9), P. 3259 - 3263

Published: April 19, 2021

Monofluoroalkenes normally act as metabolically stable bioisosteres for amide groups (-NH-CO-) and have widespread applications in drug discovery. Additionally, they are widely used building blocks organic synthesis. In this study, the Cu/Pd-catalyzed cis-borylfluoroallylation of alkynes was achieved, providing a modular general tactic preparation monofluorinated alkene scaffolds with high regioselectivity stereoselectivity. Moreover, an array synthetic can be generated by downstream transformations.

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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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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Catalytic Diversification of gem‐Difluorocyclopropanes: Recent Advances and Challenges

ChemCatChem, Journal Year: 2022, Volume and Issue: 14(24)

Published: Aug. 11, 2022

Abstract gem ‐Difluorocyclopropanes (F 2 CPs) have aroused considerable attention not only from the structural perspective but also due to their ability participate in various valuable transformations. This Review summarizes advances catalytic ring‐opening reactions of ‐F CPs, especially emphasizing reactivities and applications those non‐activated ones under transition‐metal catalysis. Their achievements, synthetic limitations are discussed with aim stimulate enthusiasm for further development.

Language: Английский

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Chemo‐, Stereo‐ and Regioselective Fluoroallylation/Annulation of Hydrazones with gem‐Difluorocyclopropanes via Tunable Palladium/NHC Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(23)

Published: April 4, 2023

Defluorinative manipulation of polyfluorinated molecules has shown great promise due to its granting synthetic versatility inert C-F bonds. The development chemo-, stereo- and regioselective strategies realize highly efficient formation either the linear/branched or E/Z products from gem-difluorocyclopropanes (gem-F2 CPs) is a challenging task. Herein, we have realized palladium/NHC-catalyzed fluoroallylation/annulation hydrazones with gem-F2 CPs that incorporate hydrazone N2 moiety into products. thermodynamically unstable fluorinated E-allylation aryl ketone were obtained for first time, while di-alkyl yielded monofluorinated branched selectivity under similar reaction conditions. With aldehyde hydrazones, two kinds pyrazoles via defluorinative allylation/annulation cascade, in which different carbon atoms could be incorporated pyrazole rings regiospecifically. DFT calculations revealed divergent was kinetically controlled final C-C bond proceeded through 7-membered TS.

Language: Английский

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