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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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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Expanding Reaction Profile of Allyl Carboxylates via 1,2-Radical Migration (RaM): Visible-Light-Induced Phosphine-Catalyzed 1,3-Carbobromination of Allyl Carboxylates

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(15), P. 8275 - 8284

Published: April 5, 2023

Allyl carboxylates are useful synthetic intermediates in a variety of organic transformations, including catalytic nucleophilic/electrophilic allylic substitution reactions and 1,2-difunctionalization reactions. However, the 1,3-difunctionalization allyl remains elusive. Herein, we report first photoinduced, phosphine-catalyzed 1,3-carbobromination carboxylates, affording range valuable substituted isopropyl (sIPC). The transformation has broad functional group tolerance, is amenable to late-stage modification complex molecules gram-scale synthesis, expands reaction profiles phosphine catalysis. Preliminary experimental computational studies suggest non-chain-radical mechanism involving formation an electron donor-acceptor complex, 1,2-radical migration (RaM), Br-atom transfer processes. We anticipate that 1,2-RaM reactivity radical will both serve as platform for development new transformations synthesis.

Language: Английский

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Cobalt-Catalyzed Enantioselective Cross-Electrophile Couplings: Stereoselective Syntheses of 5–7-Membered Azacycles

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(30), P. 16464 - 16473

Published: July 21, 2023

Cobalt complexes of chiral pyrox ligands catalyzed enantioselective reductive couplings nonconjugated iododienes with aryl iodides or alkenyl bromides. The reaction enabled stereoselective syntheses 5-7-membered azacycles carrying quaternary stereocenters. Mechanistically, cross-electrophile selectivity originated from selective coupling alkylcobalt(I) generated after cyclization iodides.

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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Nickel‐Catalyzed Cross‐Electrophile 1,2‐Silyl‐Arylation of 1,3‐Dienes with Chlorosilanes and Aryl Bromides

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(4)

Published: Nov. 26, 2022

Abstract Catalytic, three‐component, cross‐electrophile reactions have recently emerged as a promising tool for molecular diversification, but studies focused mainly on the alkyl‐carbonations of alkenes. Herein, scope this method has been extended to conjugated dienes and silicon chemistry through silylative difunctionalization 1,3‐dienes with chlorosilanes aryl bromides. The reaction proceeds under mild conditions afford 1,2‐linear‐silylated products, selectivity that is different those obtained from conventional methods via an intermediary H(C)‐η 3 ‐π‐allylmetal species. Preliminary mechanistic reveal chlorosilane reacts 1,3‐diene first then couples bromide.

Language: Английский

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Asymmetric imino-acylation of alkenes enabled by HAT-photo/nickel cocatalysis

Chemical Science, Journal Year: 2023, Volume and Issue: 14(23), P. 6449 - 6456

Published: Jan. 1, 2023

By merging nickel-mediated facially selective aza-Heck cyclization and radical acyl C-H activation promoted by tetrabutylammonium decatungstate (TBADT) as a hydrogen atom transfer (HAT) photocatalyst, we accomplish an asymmetric imino-acylation of oxime ester-tethered alkenes with readily available aldehydes the source, enabling synthesis highly enantioenriched pyrrolines bearing acyl-substituted stereogenic center under mild conditions. Preliminary mechanistic studies support Ni(i)/Ni(ii)/Ni(iii) catalytic sequence involving intramolecular migratory insertion tethered olefinic unit into Ni(iii)-N bond enantiodiscriminating step.

Language: Английский

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Nickel/Quinim Enabled Asymmetric Carbamoyl‐Acylation of Unactivated Alkenes

Chinese Journal of Chemistry, Journal Year: 2023, Volume and Issue: 41(14), P. 1673 - 1678

Published: Feb. 14, 2023

Comprehensive Summary Transition metal‐catalyzed difunctionalization of tethered alkene has emerged as a prevailing tool for the expedient construction synthetically valuable cyclic compounds. However, most efforts have been devoted to reaction styrene‐type substrates due their rigid scaffold and high reactivity. With respect nonaromatic olefin, especially mono‐substituted alkene, still remains largely underdeveloped. Herein, we disclose nickel/Quinim complex TBADT‐cocatalyzed asymmetric carbamoyl‐acylation unactivated on carbamoyl chlorides with diverse aldehydes. The exhibits broad substrate scope good functional group tolerance, well efficiency enantioselectivity. Both monosubstituted 1,1‐substituted alkenes can work either aliphatic or aromatic aldehydes under current protocol, providing convenient access an array medicinally useful chiral γ‐lactams derivatives bearing convertible acyl functionality. This showcases more application possibilities Quinim ligand in future catalytic transformations.

Language: Английский

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Enantioselective Synthesis of Isoindolinone by Palladium-Catalyzed Aminoalkynylation of O-Phenyl Hydroxamic Ethers with Alkynes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(7), P. 4320 - 4326

Published: Feb. 9, 2024

A highly efficient palladium-catalyzed asymmetric tandem aza-Heck/Sonogashira coupling reaction of O-phenyl hydroxamic ethers with terminal alkynes is described. This protocol enables versatile access to challenging chiral isoindolinone derivatives bearing a quaternary stereogenic center. The aminoalkynylation shows broad functional group tolerance and allows the straightforward preparation isoindolinones high efficiency excellent enantioselectivity under mild conditions. DFT calculations were performed disclose mechanism origins enantioselectivity.

Language: Английский

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Recent Advances in N-O Bond Cleavage of Oximes and Hydroxylamines to Construct N-Heterocycle

Molecules, Journal Year: 2023, Volume and Issue: 28(4), P. 1775 - 1775

Published: Feb. 13, 2023

Oximes and hydroxylamines are a very important class of skeletons that not only widely exist in natural products drug molecules, but also synthon, which have been used industrial production. Due to weak N-O σ bonds oximes hydroxylamines, they can be easily transformed into other functional groups by bond cleavage. Therefore, the synthesis N-heterocycle using as nitrogen sources has attracted wide attention. Recent advances for through transition-metal-catalyzed radical-mediated cyclization classified type rings summarized. In this paper, recent cleavage reviewed. We hope review provides new perspective on field, reference develop environmentally friendly sustainable methods.

Language: Английский

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