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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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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Selective Three-Component Reductive Alkylalkenylation of Unbiased Alkenes via Carbonyl-Directed Nickel Catalysis

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(15), P. 9779 - 9789

Published: July 27, 2022

A Ni-catalyzed enantioselective reductive three-component alkylalkenylation of β,γ-alkenyl ketones with cis-alkenyl iodides and fluoroalkyl in the presence Mn is reported. By leveraging five-membered nickellacycles stabilized by pendant ketone group chiral bis(oxazoline) (BiOx) ligand, this protocol allows efficient access to enantioenriched β-alkenyl from simple starting materials. diverse electronically unbiased alkenes beyond that enables regioselective construction two C(sp3)–C(sp3) C(sp3)–(sp2) bonds one single operation also demonstrated.

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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Copper‐Catalyzed Dynamic Kinetic C−P Cross‐Coupling/Cyclization for the Concise Asymmetric Synthesis of Six‐, Seven‐ and Eight‐MemberedP‐Stereogenic Phosphorus Heterocycles

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(24)

Published: March 29, 2022

Abstract A copper‐catalyzed asymmetric aryl C−P cross‐coupling/cyclization reaction was successfully developed via dynamic kinetic transformation (DYKAT) under mild conditions. This study provides a general and simple method for the catalytic enantioselective synthesis of stable six‐, seven‐ eight‐membered P‐stereogenic phosphorus heterocycles with excellent enantioselectivities moderate to high yields. One‐pot gram‐scale P‐heterocycle from commercially available materials also accomplished enantioselectivity yield.

Language: Английский

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Enantioselective nickel-catalyzed dicarbofunctionalization of 3,3,3-trifluoropropene

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

Published: Sept. 21, 2022

Despite paramount applications of chiral trifluoromethylated compounds in medicinal chemistry and materials science, limited strategies have been developed for catalytic asymmetric synthesis such valuable fluorinated structures. Here, we report a nickel catalyzed enantioselective dicarbofunctionalization inexpensive industrial chemical 3,3,3-trifluoropropene (TFP) with readily available tertiary alkyl aryl iodides. The reaction overcomes the β-F elimination side TFP, proceeds efficiently under mild conditions. protocol possesses advantages, as synthetic convenience, high enantioselectivity, excellent functional group tolerance, providing rapid straightforward access to interest.

Language: Английский

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Enantioselective Reductive Cross-Couplings of Olefins by Merging Electrochemistry with Nickel Catalysis

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(44), P. 23910 - 23917

Published: Oct. 26, 2023

The merger of electrochemistry and transition metal catalysis has emerged as a powerful tool to join two electrophiles in an enantioselective manner. However, the development electroreductive cross-couplings olefins remains challenge. Inspired by advantages synergistic use with nickel catalysis, we present here Ni-catalyzed cross-coupling acrylates aryl halides alkyl bromides, which affords chiral α-aryl carbonyls good excellent enantioselectivity. Additionally, this catalytic reaction can be applied (hetero)aryl chlorides, is difficult achieve other methods. combination cyclic voltammetry analysis electrode potential studies suggests that NiI species activates oxidative addition bromides single-electron transfer.

Language: Английский

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Enantioselective Nickel-Catalyzed Reductive Aryl/Alkenyl–Cyano Cyclization Coupling to All-Carbon Quaternary Stereocenters

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(11), P. 4776 - 4782

Published: March 9, 2022

An enantioselective nickel-catalyzed intramolecular reductive cross-coupling of C(sp2) electrophiles and cyano groups is reported. Enantioenriched CN-containing all-carbon quaternary stereocenters are assembled by desymmetrizing cyclization aryl/alkenyl halide-tethered malononitriles. The use an organic reductant, (EtO)2MeSiH, crucial to the enantioselectivity reactivity. Applications method demonstrated through synthesis bioactive molecules their cyanated analogues total natural product diomuscinone. This study exhibits potential coupling strategies access structurally rigid synthetically versatile from readily available starting materials.

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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Nickel-Catalyzed Reductive [4 + 1] Sila-Cycloaddition of 1,3-Dienes with Dichlorosilanes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(24), P. 13008 - 13014

Published: June 7, 2023

Transition-metal-catalyzed sila-cycloaddition has been a promising tool for accessing silacarbocycle derivatives, but the approach limited to selection of well-defined sila-synthons. Herein, we demonstrate potential chlorosilanes, which are industrial feedstock chemicals, this type reaction under reductive nickel catalysis. This work extends scope coupling from carbocycle synthesis and single C-Si bond formation reactions. The proceeds mild conditions shows good substrate functionality tolerance, it offers new access silacyclopent-3-enes spiro silacarbocycles. optical properties several dithienosiloles as well structural variations products demonstrated.

Language: Английский

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