Iodoarene-directed photoredox β-C(sp³)–H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer and hydrogen atom transfer

Chemical Science, Год журнала: 2024, Номер 15(17), С. 6522 - 6529

Опубликована: Янв. 1, 2024

Site selective functionalization of inert remote C(sp

Язык: Английский

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Palladium-Catalyzed Annulations via Sequential C–H Activations of C(sp²)–H/C(sp³)–H or C(sp³)–H/C(sp³)–H Bonds

ACS Catalysis, Год журнала: 2024, Номер 14(9), С. 6535 - 6546

Опубликована: Апрель 15, 2024

Palladium-catalyzed C–H annulation reactions represent a compelling strategy to construct complex ring systems with high step economy. While there are many approaches annulate structures by activation of single bond, transformations that proceed multiple bonds less explored. This is especially true for examples where one the reacting located at an sp3 center. However, exciting developments in palladium-catalyzed continue expand scope these and provide innovative strategies challenging carbon–carbon bonds. From discoveries, sequential activations have emerged as powerful tool access through C(sp2)–H/C(sp3)–H or C(sp3)–H/C(sp3)–H In this Perspective, we showcase recent use order highlight synthetic potential activation-enabled annulations inspire future disconnections diverse scaffold synthesis.

Язык: Английский

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Photoredox Site-Selective C(sp³)–H Alkylation of 1-(o-Iodoaryl)-alkan-1-ones with Activated Alkenes Enabled by Hydrogen Atom Transfer

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

A visible-light-mediated photoredox catalysis for β-C(sp3)–H alkylation of 1-(o-iodoaryl)alkan-1-ones with alkenes via 1,5-hydrogen atom transfer and alkene alkylarylation to produce diverse β-alkyl arylalkanones containing a quaternary carbon center is presented. This method applicable wide range activated alkenes. Mechanistic studies suggest that the reaction involves radical process.

Язык: Английский

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Enantioselective β-C(sp³)–H Nucleophilic Tosylation of Native Amides: A Synthetic Platform for Chiral Methyl Stereocenters

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Май 31, 2025

Enantioselective oxygenation of unactivated C(sp3)-H bonds via asymmetric metalation remains an unsolved challenge. Herein we report the development a Pd-catalyzed, enantioselective tosylation native amides with NaOTs as nucleophile, representing rare example C-H functionalization nucleophilic coupling partner. High enantioselectivity in this reaction is achieved by chiral monoprotected amino sulfonamide (MPASA) ligands. Substantial enhancement silver salt additives was also observed. Through desymmetrization readily available isopropyl moiety, structurally diverse β-tosylated bearing α-methyl stereocenter were obtained high yield and enantioselectivity, which complements current enzymatic method for making Roche ester synthon. The tosylated products are highly versatile building blocks further diversifications nitrogen, oxygen, other nucleophiles, thus providing platform constructing methyl stereocenters.

Язык: Английский

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Surpassing the Limited Coordination Affinity of Native Amides by Introducing Pyridone-Pd-AgOAc Clusters to Promote Distal γ-C(sp³)–H Arylation

ACS Catalysis, Год журнала: 2024, Номер 14(6), С. 3798 - 3811

Опубликована: Фев. 22, 2024

The utilization of weak coordination in promoting site-selective C(sp3)–H functionalization is immense importance. Herein, we report a Pd-catalyzed distal γ-C(sp3)–H arylation that harnesses the affinity keto groups with native noncoordinating amide moiety. current protocol overcomes one major challenges associated diversification synthetic modular frameworks quaternary centers: controlling mono- vs difunctionalization chemically equivalent C–H bonds. developed condition overrides interference acidic α-hydrogen for possible side reactions amides and delivers exclusive formation γ-monoarylated product. association 2-hydroxy pyridine ligands bearing electron-withdrawing substituents demonstrated best partnership Pd–Ag hetero-bimetallic complex to achieve this activation range aliphatic absence any other exogenous ligand. Here, an array mechanistic measurements helped us realize role A density functional theory (DFT) study was performed on four different computational models elucidate working principle single pyridone ligand externally installed strong chelating donor motifs. reaction proceeds sequentially through three primary stages: initial bond amide, succeeded by oxidative addition aryl halide, culminating reductive elimination, which facilitates C(sp2)–C(sp3) coupling between moieties. silver salt remained essential not only successful but also turning over catalytic cycle.

Язык: Английский

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Ligand-Enabled Palladium-Catalyzed β-C(sp³)–H Biarylation of Native Amides with Cyclic Diaryliodonium Salts

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Май 2, 2025

Herein, we report a Pd-catalyzed β-C(sp3)-H biarylation of native amides using diaryliodonium salts. A pyridine-3-sulfonic acid ligand that might stabilize the substrate-bound palladium species was found to be essential for high catalytic activity. The reaction displayed broad scope and showed excellent compatibility with diverse cyclic salts amide substrates. retained iodo functionality on product provides versatile handle further increasing molecular complexity.

Язык: Английский

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Asymmetric total synthesis of benzenoid cephalotane-type diterpenoids through a cascade C(sp2) & C(sp3)–H activation

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Май 20, 2025

Cephalotane diterpenoids, featuring unique and complicated carbon skeletons remarkable antitumor activities from the Cephalotaxus genus, have been gaining increasing attention. Herein, we report asymmetric divergent total synthesis of benzenoid cephalotane-type diterpenoids containing identical 6/6/6/5 tetracyclic bridged δ-lactone skeleton with different oxidation states. A cascade C(sp2) C(sp3)-H activation has developed to efficiently prepare characteristic synthetically challenging through a pivotal palladium/NBE-cocatalyzed process. The feature this strategy is construction three C-C bonds (two C(sp2)-C(sp3) one C(sp3)-C(sp3) bond) formation two cycles chiral centers in single step. application method for rapid assembly demonstrated concise cephanolides A-D (1-4) ceforalide B (5) via late-stage modification.

Язык: Английский

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Palladium-Catalyzed Methylene β-C–H Fluorination of Native Amides

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Июнь 5, 2025

Selective fluorination of C(sp3)-H bonds is a highly valuable transformation in organic synthesis and drug discovery. However, achieving methylene C-H native substrates remains significant challenge, as it typically requires external directing groups to facilitate catalyst-substrate binding. Herein, we report ligand-accelerated Pd-catalyzed β-C-H amides using bidentate neutral amide-pyridone ligand. This ligand design features the enhancement interactions via stabilization cationic palladium center acceleration activation, enabling stereo- site-selective under relatively mild conditions. Notably, Pd(II)-catalyzed activation weakly coordinating has not been reported date. method compatible with derived from selected molecules Weinreb amides, demonstrating potential utility discovery other applications.

Язык: Английский

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Synthesis of Chiral Saturated Heterocycles Bearing Quaternary Centers via Enantioselective β-C(sp³)–H Activation of Lactams

Journal of the American Chemical Society, Год журнала: 2024, Номер 147(2), С. 1427 - 1433

Опубликована: Дек. 31, 2024

The development of catalytic methods for the synthesis enantiopure saturated heterocycles has been a long-standing challenge in asymmetric catalysis. We describe first highly enantioselective palladium-catalyzed β-C(sp3)-H arylation and olefination lactams preparation various chiral N-heterocycles bearing quaternary carbon centers. presence strongly electron-withdrawing groups on bifunctional MPAThio ligand is crucial to reactivity weakly coordinating lactams. resulting enantioenriched are readily converted family piperidines imides that desirable drug discovery.

Язык: Английский

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Cyclization Through Dual C(sp³)−H Functionalization

Advanced Synthesis & Catalysis, Год журнала: 2024, Номер 366(17), С. 3542 - 3563

Опубликована: Июль 11, 2024

Abstract C( sp 3 )−H functionalization methods have been widely employed in many organic transformations such as cyclization reactions, heterocycle synthesis, cross‐coupling protocols, and photochemical transformations. Among these transformations, reaction through offers a direct route to convert simple linear substrates complex products. There are three common modes of utilizing bonds reactions including single, double, dual functionalization. As the most challenging mode, refers converting two separate one molecule into desired C−Z which can be reactions. Cyclization via classified based on C−H reactivities. Therefore, categorized classes types activated‐activated, activated‐unactivated, unactivated‐unactivated bonds. Most published reports for involve activated‐activated However, number reported papers other has growing. This review focuses protocols used categorizes

Язык: Английский

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