Nickel-Catalyzed Ligand-Controlled Selective Reductive Cyclization/Cross-Couplings

Accounts of Chemical Research, Год журнала: 2023, Номер 56(5), С. 515 - 535

Опубликована: Янв. 23, 2023

ConspectusThe use of quaternary stereocenters during lead candidate optimization continues to grow because improved physiochemical and pharmacokinetic profiles compounds with higher sp3 fraction. Pd-catalyzed redox-neutral alkene difunctionalization involving carbopalladation alkenes followed by nucleophilic-trapping σ-alkyl-palladium intermediates has been developed as an efficient method construct stereocenters. However, the low chemoselectivity air sensitivity organometallic nucleophiles, well their availability accessibility, limit scope application this elegant strategy. Recently, Ni-catalyzed reductive cross-coupling evolved into a privileged strategy easily valuable C(sp3)-C bonds. Despite great progress, enantioselective coupling C(sp3) electrophiles still relies on activated or functionalized alkyl precursors, which are often unstable require multiple steps prepare. Therefore, via selective cyclization/cross-coupling was developed. This not only offers robust practical alternative for traditional but also provides strategic complementarity electrophiles. In Account, we summarize latest results from our laboratory topic. These findings mainly include explorations in modulating enantioselectivity cyclization mode cyclization/cross-couplings.We will first discuss chiral heterocycles focus effects ligands, reductants, additives roles cross-coupling. A wide range have explored, including aryl halides, vinyl alkynyl gem-difluoroalkenes, CO2, trifluoromethyl alkenes, cyano The synthetic potential approach demonstrated synthesis biologically active natural products drug molecules. Second, detail how tune steric nickel catalysts modifying bipyridine ligands regiodivergent cyclization/cross-couplings. Specifically, bidentate favors exo-selective cyclization/cross-coupling, while carboxylic acid-modified ligand permits endo-selective cyclization/cross-coupling. We show activate amide substrate altering electronic properties substituents nitrogen, thereby enabling nucleophilic addition halides carbonyls. Further investigation led tunable cyclization/cross-couplings (addition carbonyl vs 7-endo-cyclization) divergent pharmacologically important 2-benzazepine frameworks. Finally, serendipitously discover that changing oxidation state can control migratory aptitude different groups, thus providing switchable skeletal rearrangement transformation is high value it represents conceptually unprecedented new C-C bond activation. Thus, Account summarizes methods allow formation using variety insight relationship between structure, substrate, selectivity.

Язык: Английский

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Modular Synthesis of Multifunctionalized CF₃-Allenes through Selective Activation of Saturated Hydrocarbons

ACS Catalysis, Год журнала: 2022, Номер 12(16), С. 10207 - 10221

Опубликована: Авг. 5, 2022

Catalytic 1,4-dicarbofunctionalization of 1,3-enynes is a powerful strategy for the synthesis polysubstituted allenes. Despite impressive progress, such still restricted to use alkyl-metallic reagents or pre-activated radical precursors, thus limiting its functional group compatibility and atom economy. Herein, we report that through combination decatungstate photo-hydrogen transfer nickel catalysis, three-component 2-trifluoromethyl-1,3-enynes achieved. This allows modular tetrasubstituted CF3-allenes under exceptionally mild conditions. A variety electrophiles as aryl bromides, alkenyl acyl chlorides, alkynyl bromides were successfully employed traps lead desired products. Another significant advantage most abundant hydrocarbons are used feedstocks, wide range synthetically versatile groups complex drug-like structures can be easily incorporated. Based on experimental density theories, possible catalytic cycle involving 1,3-nickel rearrangement proposed.

Язык: Английский

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Nickel‐Catalyzed Defluorinative Asymmetric Cyclization of Fluoroalkyl‐Substituted 1,6‐Enynes for the Synthesis of Seletracetam

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(46)

Опубликована: Сен. 23, 2022

Abstract The introduction of fluorine‐containing groups into organic molecules can significantly affect their physical and chemical properties has long been used as an effective strategy for drug discovery development. Consequently, the development catalytic asymmetric methods synthesis heterocycles is highly desirable sought after. Herein, we describe a nickel‐catalyzed defluorinative cyclization fluoroalkyl‐substituted 1,6‐enynes, providing expedient access to synthetically attractive 4‐fluorovinyl‐substituted 2‐pyrrolidones in good yields with remarkable high levels chemo‐, regio‐, enantioselectivities (90–99 % ee,>35 examples). This protocol features readily available starting materials excellent functional group compatibility, exhibits complementary regioselectivity. utility this was demonstrated enantioselective antiepileptic Seletracetam.

Язык: Английский

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Enantioselective Reductive N-Cyclization–Alkylation Reaction of Alkene-Tethered Oxime Esters and Alkyl Iodides by Nickel Catalysis

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(30), С. 13461 - 13467

Опубликована: Июль 25, 2022

Asymmetric cross-electrophile difunctionalization of tethered alkenes has become a powerful tool for the production chiral cyclic scaffolds; however, current studies all focus on carbocyclization reactions. Herein, we report an N-cyclization-alkylation reaction and thus showcase potential heterocyclization accessing new enantioenriched architectures. This work establishes approach enantioselective aza-Heck cyclization/cross-coupling sequence, which remains long-standing unsolved challenge synthetic community. The proceeds with primary, secondary, few tertiary alkyl iodides, use newly defined ligands gave highly pyrrolines improved molecular diversity under mild conditions. presence imine functionality allows further structural variations.

Язык: Английский

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Synthesis of Fluorinated Compounds by Nickel-Catalyzed Defluorinative Cross-Coupling Reactions

ACS Catalysis, Год журнала: 2023, Номер 13(18), С. 12238 - 12268

Опубликована: Сен. 1, 2023

Organofluorine compounds have attracted extensive attention in various industrial fields due to their unique chemical and physical properties. Despite increasing demand a wide range of scientific fields, the synthesis organofluorine still faces several problems, such as difficulties handling fluorinating reagents control chemoselectivity. Compared with formation C–F bonds, activation functionalization carbon–fluorine bonds is very important but challenging topic synthetic chemistry. Due properties nickel, Ni-catalyzed defluorinative cross-couplings been greatly developed past few decades powerful strategies for construction fluorinated organic compounds. This Review summarizes advances cross-coupling aryl fluorides, gem-difluorovinyl trifluoromethyl

Язык: Английский

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Ni-catalyzed ligand-controlled divergent and selective synthesis

Science China Chemistry, Год журнала: 2023, Номер 66(11), С. 2951 - 2976

Опубликована: Май 5, 2023

Язык: Английский

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Nickel-catalyzed switchable arylative/endo-cyclization of 1,6-enynes

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 4, 2024

Abstract Carbo- and heterocycles are frequently used as crucial scaffolds in natural products, fine chemicals, biologically pharmaceutically active compounds. Transition-metal-catalyzed cyclization of 1,6-enynes has emerged a powerful strategy for constructing functionalized carbo- heterocycles. Despite significant progress, the regioselectivity alkyne functionalization is entirely substrate-dependent. And only exo -cyclization/cross-coupling products can be obtained, while endo -selective cyclization/cross-coupling remains elusive still poses formidable challenge. In this study, we disclose nickel-catalyzed switchable arylation/cyclization which nature ligand dictates arylation, electrophilic trapping reagents determine selectivity mode. Specifically, using commercially available 1,10-phenanthroline facilitates trans -arylation/cyclization to obtain seven-membered ring 2-naphthyl-substituted bisbox promotes cis access six-membered products. Diastereoselective cyclizations have also been developed synthesis enantioenriched piperidines azepanes, core structural elements pharmaceuticals possessing important biological activities. Furthermore, experimental density functional theory studies reveal that arylation process controlled by steric hindrance ligand; reaction mechanism involves -cyclization followed Dowd-Beckwith-type expansion form

Язык: Английский

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Stereoselective and site-divergent synthesis of C-glycosides

Nature Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Сен. 13, 2024

Язык: Английский

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Pd-Catalyzed Strain-Releasing Dyotropic Rearrangement: Ring-Expanding Amidofluorination of Methylenecyclobutanes

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

Опубликована: Март 2, 2025

Under the Pd(II)/Pd(IV) catalytic cycle, cyclization of pent-4-en-1-amine derivatives typically yields either pyrrolidines or piperidines depending on N-protecting group. We report herein an unprecedented Pd(II)-catalyzed oxidative domino process that converts readily accessible N-protected 2-(2-amidoethyl)-1-methylenecyclobutane to 1-fluoro-2-azabicyclo[3.2.1]octanes. This transformation constructs three chemical bonds under mild conditions [Pd(hfacac)2 (5.0 mol %), Selectfluor (2.0 equiv), MeCN, 60 °C, 10 min] through a sequence involving 5-exo-trig amidopalladation/Pd(II)–oxidation/chemoselective dyotropic rearrangement/C–F bond-forming reductive elimination. Notably, mode remains independent group these conditions. Furthermore, diverse functional groups can be introduced at bridgehead position bicyclic compound via apparent anti-Bredt iminium intermediate.

Язык: Английский

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Recent Advances in Ni-Catalyzed Asymmetric Reductive Difunctionalization of Alkenes

Chinese Journal of Organic Chemistry, Год журнала: 2022, Номер 42(10), С. 3302 - 3302

Опубликована: Янв. 1, 2022

Alkenes are cheap and easily available bulk industrial feedstocks.Difunctionalization of alkenes can rapidly construct complex molecules, which have broad applications in organic synthesis.Compared with traditional redox-neutral alkene difunctionalization, the reductive difunctionalization introduce two different electrophiles to both sides carbon-carbon double bond, has advantages mild reaction conditions, high functional group tolerance, no need for pre-prepared organometallic reagents.The latest research progress nickel-catalyzed is summarized.The development prospect prospected.

Язык: Английский

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