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

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(5), P. 515 - 535

Published: Jan. 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.

Language: Английский

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Enantioselective Reductive Divinylation of Unactivated Alkenes by Nickel-Catalyzed Cyclization Coupling Reaction

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(33), P. 12961 - 12967

Published: Aug. 12, 2021

Catalytic asymmetric dicarbofunctionalization of tethered alkenes has emerged as a promising tool for producing chiral cyclic molecules; however, it typically relies on aryl-tethered to form benzene-fused compounds. Herein, we report an enantioselective cross-electrophile divinylation reaction nonaromatic substrates, 2-bromo-1,6-dienes. The approach thus offers route new architectures, which are key structural motifs found in various biologically active proceeds under mild conditions, and the use t-Bu-pmrox 3,5-difluoro-pyrox ligands resulted formation divinylated products with high chemo-, regio-, enantioselectivity. method is applicable incorporation hetero- carbocycles into complex molecules.

Language: Английский

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Catalytic Desymmetric Dicarbofunctionalization of Unactivated Alkenes

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(26)

Published: March 14, 2022

The construction of multi-stereocenters by a transition metal-catalyzed cross-coupling reaction is major challenge. catalytic desymmetric functionalization unactivated alkenes remains largely unexplored. Herein, we disclose -a dicarbofunctionalization 1,6-dienes via nickel-catalyzed reductive reaction. leverage the underdeveloped chiral 8-Quinox enables Ni-catalyzed carbamoylalkylation both mono- and disubstituted to form pyrrolidinone bearing two nonadjacent stereogenic centers in high enantio- stereoselectivitives with broad functional-group tolerance. synthetic application pyrrolidinones allows rapid access complex fused-heterocycles.

Language: 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, Journal Year: 2022, Volume and Issue: 144(30), P. 13461 - 13467

Published: July 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.

Language: Английский

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Cross-Electrophile Coupling: Principles, Methods, and Applications in Synthesis

Chemical Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Cross-electrophile coupling (XEC), defined by us as the cross-coupling of two different σ-electrophiles that is driven catalyst reduction, has seen rapid progression in recent years. As such, this review aims to summarize field from its beginnings up until mid-2023 and provide comprehensive coverage on synthetic methods current state mechanistic understanding. Chapters are split type bond formed, which include C(sp

Language: Английский

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Ligand-Controlled, Nickel-Catalyzed Stereodivergent Construction of 1,3-Nonadjacent Stereocenters

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(22), P. 15453 - 15463

Published: May 25, 2024

In contrast to the asymmetric synthesis of molecules with a single stereocenter or 1,2-adjacent stereocenters, simultaneous construction acyclic 1,3-nonadjacent stereocenters via catalyst in an enantioselective and diastereoselective manner remains formidable challenge. Here, we demonstrate diastereodivergent through Ni-catalyzed reductive cyclization/cross-coupling alkene-tethered aryl bromides α-bromoamides, which represents major remaining stereochemical challenge cyclization/difunctionalization alkenes. Using Ming-Phos as ligand, diverse set oxindoles containing were obtained high levels enantio- diastereoselectivity. Mechanistic experiments density functional theory calculations indicate that magnesium salt plays key role controlling Furthermore, another complementary stereoisomeric products constructed from same starting materials using Ph-Phox ligand.

Language: Английский

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Ni-catalyzed carbamoylation of unactivated alkenes for stereoselective construction of six-membered lactams

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Oct. 10, 2022

Abstract Nitrogen-based heterocycles have aroused widespread interest due to their reoccurrence in many pharmaceuticals. Amongst these motifs, the enantioenriched lactams are ubiquitous scaffolds found myriad biologically active natural products and drugs. Recently, transition metal-catalyzed asymmetric carbamoylation has been widely employed as a straightforward arsenal for chiral lactam architecture synthesis, including β-lactam γ-lactam. However, despite extensive efforts, there still remains no protocol accomplish related δ-lactam synthesis. In this manuscript, Ni-catalyzed enantioselective of unactivated alkenes by leverage reductive dicarbofunctionalization strategy allows expedient access two types mostly common six-membered lactams: 3,4-dihydroquinolinones 2-piperidinone high yield enantioselectivity. This features with good functional group tolerance, well broad substrate scope. The newly developed 8-Quinox skeleton ligand is key parameter transformation, which significantly enhances reactivity

Language: Английский

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Recent Advances in Ni-Catalyzed Asymmetric Reductive Difunctionalization of Alkenes

Chinese Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 42(10), P. 3302 - 3302

Published: Jan. 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.

Language: Английский

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Nickel-Catalyzed Asymmetric Cross-Electrophile trans-Aryl-Benzylation of α-Naphthyl Propargylic Alcohols

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(10), P. 6795 - 6803

Published: May 3, 2023

Herein, we report a nickel-catalyzed asymmetric three-component trans-dicarbofunctionalization of β-substituted α-naphthyl propargylic alcohols using readily available aryl and benzyl halides as the coupling partners under reductive conditions. This cross-electrophile strategy enables synthesis various axially chiral allylic bearing tetrasubstituted olefinic unit in complete regio- E selectivity, well high enantiocontrol. Relying on hydroxyl group functional handle, such structural motifs are successfully derivatized into diverse functional-group-rich alkenes.

Language: Английский

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Development of novel transition metal-catalyzed synthetic approaches for the synthesis of a dihydrobenzofuran nucleus: a review

RSC Advances, Journal Year: 2024, Volume and Issue: 14(21), P. 14539 - 14581

Published: Jan. 1, 2024

The synthesis of dihydrobenzofuran scaffolds bears pivotal significance in the field medicinal chemistry and organic synthesis. These heterocyclic hold immense prospects owing to their significant pharmaceutical applications as they are extensively employed essential precursors for constructing complex frameworks. Their versatility importance make them an interesting subject study researchers scientific community. While exploring synthesis, have unveiled various novel efficient pathways assembling core. In wake extensive data being continuously reported each year, we outlined recent updates (post 2020) on methodological accomplishments employing catalytic role several transition metals forge functionalities.

Language: Английский

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