Palladium‐Catalyzed Defluorinative Alkylation of gem‐Difluorocyclopropanes: Switching Regioselectivity via Simple Hydrazones

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(23), С. 13098 - 13104

Опубликована: Март 23, 2021

Abstract Conventional approaches for Pd‐catalyzed ring‐opening cross‐couplings of gem ‐difluorocyclopropanes with nucleophiles predominantly deliver the β‐fluoroalkene scaffolds (linear selectivity). Herein, we report a cooperative strategy that can completely switch reaction selectivity to give alkylated α‐fluoroalkene skeletons (branched The unique reactivity hydrazones enables analogous inner‐sphere 3,3′‐reductive elimination driven by denitrogenation, as well assistance steric‐embedded N ‐heterocyclic carbene ligand, are key regioselectivity. A wide range derived from naturally abundant aryl and alkyl aldehydes applicable, various ‐difluorocyclopropanes, including modified pharmaceutical biological molecules, be efficiently functionalized high value α‐fluorinated alkene motifs under mild conditions.

Язык: 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, Год журнала: 2021, Номер 60(19), С. 10626 - 10631

Опубликована: Фев. 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.

Язык: Английский

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Access to Divergent Fluorinated Enynes and Arenes via Palladium-Catalyzed Ring-Opening Alkynylation of gem-Difluorinated Cyclopropanes

Organic Letters, Год журнала: 2020, Номер 22(4), С. 1414 - 1419

Опубликована: Фев. 3, 2020

Herein, we describe a palladium-catalyzed alkynylation of gem-difluorinated cyclopropanes via C–C bond activation/C–F cleavage, followed by C–C(sp) coupling. The new approach proceeds with broad substrate scope under mild reaction conditions, whereas both 1,1-disubstituted and complex-molecule-modified react smoothly high stereoselectivity. developed method provides efficient convenient ways access to diversity important fluorinated enynes arenes slightly modification the conditions.

Язык: Английский

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

Organic Letters, Год журнала: 2021, Номер 23(9), С. 3259 - 3263

Опубликована: Апрель 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.

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

Organic Letters, Год журнала: 2021, Номер 23(12), С. 4920 - 4924

Опубликована: Июнь 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.

Язык: Английский

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

Organic Letters, Год журнала: 2022, Номер 24(11), С. 2093 - 2098

Опубликована: Март 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.

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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