Catalytic Asymmetric Difluoroalkylation Using In Situ Generated Difluoroenol Species as the Privileged Synthon

Advanced Science, Год журнала: 2024, Номер 11(14)

Опубликована: Фев. 6, 2024

A robust and practical difluoroalkylation synthon, α,α-difluoroenol species, which generated in situ from trifluoromethyl diazo compounds water the presence of dirhodium complex, is disclosed. As compared to presynthesized difluoroenoxysilane formed difluoroenolate under basic conditions, this difluoroenol intermediate displayed versatile reactivity, resulting dramatically improved enantioselectivity mild conditions. demonstrated catalytic asymmetric aldol reaction Mannich reactions with ketones or imines chiral organocatalysts, quinine-derived urea, phosphoric acid (CPA), respectively, relay catalysis strategy provides an effective platform for applying fluorination chemistry. Moreover, method features a novel 1,2-difunctionalization process via installation carbonyl motif alkyl group on two vicinal carbons, complementary protocol metal carbene gem-difunctionalization reaction.

Язык: Английский

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Recent advances in cascade reactions and their mechanistic insights: a concise strategy to synthesize complex natural products and organic scaffolds

Organic & Biomolecular Chemistry, Год журнала: 2022, Номер 20(18), С. 3653 - 3674

Опубликована: Янв. 1, 2022

This review features a broad interest in compiling range of cascade transformations under various classifications based on nature and reactivity the main ingredient to solve diverse challenges organic synthesis create fascinating molecules.

Язык: Английский

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Construction of Chiral Quaternary Carbon Centers via Asymmetric Metal Carbene gem‐Dialkylation

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(26)

Опубликована: Май 2, 2023

The catalytic asymmetric construction of all-carbon quaternary stereocenters has received tremendous interest over the past decades, and numerous efficient protocols have been disclosed based on formation one C-C bond between two assembling reactants. However, use multi-component reactions that build bonds same carbonic center with concomitant assembly is rare remains challenging. Herein, we disclose an enantioselective three-component reaction α-diazo ketones alkenes 1,3,5-triazines under dirhodium/chiral phosphoric acid cooperative catalysis, which leads to a practical atom-economic synthesis poly-functionalized chiral bear α-quaternary stereocenter in generally good high yields excellent enantioselectivities. In comparison previous method for tertiary via carbene gem-difunctionalization reactions, this features unprecedented gem-dialkylation process sequential installation reaction, providing essential complement using common readily available starting materials.

Язык: Английский

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Cooperative Bimetallic Catalysis via One‐Metal/Two‐Ligands: Mechanistic Insights of Polyfluoroarylation‐Allylation of Diazo Compounds

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(34)

Опубликована: Июнь 16, 2023

Metal/ligand in situ assembly is crucial for tailoring the reactivity & selectivity transition metal catalysis. Cooperative catalysis via a single metal/two ligands still underdeveloped, since it rather challenging to harness distinct profiles of species generated by self-assembly precursor with mixture different ligands. Herein, we report catalytic system composed three-component reaction polyfluoroarene, α-diazo ester, and allylic electrophile, leading highly efficient construction densely functionalized quaternary carbon centers, that are otherwise hardly accessible. Mechanistic studies suggest this follows cooperative bimetallic pathway two catalysts profiles, which assembled from work concert escort transformation.

Язык: Английский

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Stereoselective gem-Difunctionalization of Diazo Compounds with Vinyl Sulfoxonium Ylides and Thiols via Metalloradical Catalysis

ACS Catalysis, Год журнала: 2024, Номер 14(4), С. 2805 - 2815

Опубликована: Фев. 8, 2024

Multicomponent reactions that involve carbenes with nucleophiles and electrophiles have demonstrated broad applications in synthetic chemistry. However, because of the high reactivity transient carbenes, involving two carbene precursors nucleophile presence a metal catalyst remain unexplored. Herein, three-component stereoselective gem-difunctionalization diazo compounds thiols vinyl sulfoxonium ylide is disclosed via Co(II)-based metalloradical catalysis. The key aspect present strategy to exploit intrinsic difference ylides thiol catalysts. Doyle–Kirmse rearrangement sulfonium involves convergent assembly situ-generated intermediates, such as allyl sulfide α- metalloalkyl radical complex, provide expeditious access tertiary scaffolds. Combined experimental quantum chemical calculations unveil intricate mechanism this reaction. Furthermore, theoretical studies on noncovalent interactions selectivity-determining transition states explain origin experimentally obtained diastereoselectivity.

Язык: Английский

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Efficient Synthesis of Diaryl Quaternary Centers by Rh(II)/Xantphos Catalyzed Relay C−H Functionalization and Allylic Alkylation

Chemistry - A European Journal, Год журнала: 2022, Номер 29(3)

Опубликована: Окт. 14, 2022

A three-component reaction of N, N-disubstituted aniline, α-diazo ester, and an allylic electrophile has been realized by [Rh(II)]2 /Xantphos catalysis, providing a direct access to various aniline derivatives bearing diaryl quaternary centers in good yields. The synthetic utility this protocol was demonstrated facile derivatization the products for preparation biologically relevant molecules structural scaffolds, which offers high potential increasing molecular diversity. Mechanistic studies identified α, α-diarylacetate species as active intermediate, thereby revealing presence C(sp2 )-H functionalization derivatives/allylic alkylation cascade attractive catalytic transformation.

Язык: Английский

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Palladium-Catalyzed Three-Component Selective Aminoallylation of Diazo Compounds

Organic Letters, Год журнала: 2022, Номер 24(23), С. 4160 - 4164

Опубликована: Июнь 3, 2022

We describe a Xantphos-containing dinuclear palladium complex-enabled geminal aminoallylation of diazocarbonyl compounds, which selectively provides range quaternary α-amino esters. Direct N–H insertion, allylic alkylation amino nucleophiles, and diene formation were not observed under standard conditions. Mechanistic studies indicated that relayed pathway via allylation the insertion product or [2,3]-sigmatropic rearrangement an ylide intermediate was unlikely.

Язык: Английский

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Catalytic Asymmetric P–H Insertion Reactions

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(36), С. 20031 - 20040

Опубликована: Авг. 29, 2023

Albeit notable endeavors in enantioselective carbene insertion into X–H bonds (X = C, O, N, S, Si, B), the catalytic asymmetric P–H reactions still stand for a long-lasting challenge. By merging transition-metal catalysis with organocatalysis, we achieve scalable transformation between diazo pyrazoleamides and H-phosphine oxides that upon subsequent reduction delivers wide variety of optically active β-hydroxyl phosphine good yields high enantioselectivity. The achiral copper catalyst fosters carbenoid bond, while chiral cinchona alkaloid-derived organocatalyst controls outcome. Density functional theory (DFT) calculations further reveal chelates to organocatalyst, enhances its acidity, accordingly promotes proton transfer. Our work showcases potential combining organocatalysis realize elusive reactions.

Язык: Английский

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Rh(II)/Pd(0) Dual-Catalyzed Regio-Divergent Three-Component Propargylic Substitution

JACS Au, Год журнала: 2023, Номер 3(10), С. 2862 - 2872

Опубликована: Сен. 25, 2023

Regio-divergent propargylic substitution to generate functionally diverse products from identical starting materials remains a formidable challenge, probably due the unpredictable regiochemical complexity. In practically, synthesis of α-quaternary propargylic-substituted is still much less developed, and preprepared nucleophiles are generally applied in this type reaction with substrates, which limits efficiency diversity obtained products. Herein, we disclose unprecedented three-component α-diazo esters amines carbonates under dirhodium/palladium dual catalysis. The key success multicomponent avoid two-component side reactions through tandem process dirhodium(II)-catalyzed carbene insertion palladium-catalyzed regiodivergent substitution. judicious selection diphosphine (dppf) or monophosphine (tBuBrettphos) as ligand crucial for different switchable way, 1,3-dienyl propargylated products, high regio- chemoselectivities.

Язык: Английский

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Asymmetric N‐Alkylation of 1H‐Indoles via Carbene Insertion Reaction

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(47)

Опубликована: Окт. 11, 2023

An intermolecular enantioselective N-alkylation reaction of 1H-indoles has been developed by cooperative rhodium and chiral phosphoric acid catalyzed N-H bond insertion reaction. N-Alkyl indoles with newly formed stereocenter adjacent to the indole nitrogen atom are produced in good yields (up 95 %) excellent enantioselectivities >99 % ee). Importantly, both α-aryl α-alkyl diazoacetates tolerated, which is extremely rare asymmetric X-H (X=N, O, S et al.) C-H reactions. With this method, only 0.1 mol catalyst 2.5 required complete conversion as well achieve high enantioselectivity. Computational studies reveal relay acid, origin chemo stereoselectivity.

Язык: Английский

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