Carbon–Carbon Bond Cleavage for Late-Stage Functionalization

Chemical Reviews, Год журнала: 2023, Номер 123(22), С. 12313 - 12370

Опубликована: Ноя. 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

Язык: Английский

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

ACS Catalysis, Год журнала: 2021, Номер 11(19), С. 11960 - 11965

Опубликована: Сен. 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.

Язык: Английский

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

ACS Catalysis, Год журнала: 2022, Номер 12(11), С. 6495 - 6505

Опубликована: Май 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.

Язык: Английский

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

ACS Catalysis, Год журнала: 2022, Номер 12(15), С. 8857 - 8867

Опубликована: Июль 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.

Язык: Английский

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Catalytic Diversification of gem‐Difluorocyclopropanes: Recent Advances and Challenges

ChemCatChem, Год журнала: 2022, Номер 14(24)

Опубликована: Авг. 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.

Язык: 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, Год журнала: 2023, Номер 62(23)

Опубликована: Апрель 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.

Язык: Английский

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Pd/IPr^BIDEA-Catalyzed Hydrodefluorination of gem-Difluorocyclopropanes: Regioselective Synthesis of Terminal Fluoroalkenes

Journal of the American Chemical Society, Год журнала: 2023, Номер 146(1), С. 24 - 32

Опубликована: Окт. 13, 2023

Developing new strategies to enable chemo- and regioselective reductions is an important topic in chemical research. Herein, efficient Pd/IPr

Язык: Английский

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Palladium‐Catalyzed Fluorinative Bifunctionalization of Aziridines and Azetidines with gem‐Difluorocyclopropanes

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(42)

Опубликована: Авг. 12, 2023

Abstract An unprecedented Pd‐catalyzed fluorinative bifunctionalization of aziridines and azetidines was successfully developed via regioselective C−C C−F bond cleavage gem‐difluorocyclopropanes, leading to various β,β′‐bisfluorinated amines β,γ‐bisfluorinated amines. This reaction achieved by incorporating a 2‐fluorinated allyl group fluorine atom scissored from gem‐difluorocyclopropane in 100 % economy for the first time. The mechanistic investigations indicated that underwent amine attacking palladium complex generate η 2 ‐coordinated N‐allyl aziridine followed fluoride ligand transfer affording final β‐ γ‐fluorinated

Язык: Английский

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Regiodivergent electroreductive defluorinative carboxylation ofgem-difluorocyclopropanes

Green Chemistry, Год журнала: 2023, Номер 25(8), С. 3095 - 3102

Опубликована: Янв. 1, 2023

A regiodivergent electrochemical defluorocarboxylation of gem -difluorocyclopropanes is realized, providing access to branched and linear carboxylated monofluorinated alkenes.

Язык: Английский

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Diastereoselective Synthesis of Monofluorocyclohexenes through Photocatalyzed Cascade Cyclization of gem‐Difluoroalkenes and α,β‐Unsaturated Carbonyl Compounds

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(20)

Опубликована: Март 16, 2023

Monofluoroalkenes are nonhydrolyzable mimetics of amides. Previous work focused on the synthesis non-cyclic monofluoroalkenes. However, diastereoselective monofluorocyclohexenes from substrates is challenging. Herein, we report first photocatalyzed cascade cyclization reactions readily available α,β-unsaturated carbonyl compounds and gem-difluoroalkenes for highly functionalized monofluorocyclohexenes. The reaction shows broad substrate scope with high diastereoselectivity (>30 examples, up to 86 % yield, >20 : 1 dr). post-reaction transformations products demonstrate synthetic potential this methodology.

Язык: Английский

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