Nickel-Catalyzed Dicarbofunctionalization of Alkenes

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(15), P. 8542 - 8556

Published: July 2, 2020

1,2-Dicarbofunctionalization of alkenes has emerged as an efficient synthetic strategy for preparing substituted molecules by coupling readily available with electrophiles and/or nucleophiles. Nickel complexes serve effective catalysts owing to their tendency undergo facile oxidative addition and slow β-hydride elimination, capability access both two-electron radical pathways. Two-component alkene functionalization reactions have achieved high chemo-, regio-, stereoselectivities tethering one the partners substrate. Three-component reactions, however, often incorporate directing groups control selectivity. Only a few examples directing-group-free difunctionalizations unactivated been reported. Therefore, great opportunities exist development three-component difunctionalization broad substrate scopes tunable stereoselectivities.

Language: Английский

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Asymmetric Ni-Catalyzed Radical Relayed Reductive Coupling

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(31), P. 13515 - 13522

Published: June 29, 2020

Alkene dicarbofunctionalizations enable the streamlined construction of aliphatic structures and have thus been subject intense research efforts. Despite significant progress, catalytic asymmetric variants remain scarce. Inspired by advantages reductive cross-coupling approaches, we present here a highly efficient intermolecular Ni-catalyzed dicarbofunctionalization alkenes. Two distinct readily available electrophiles, namely, Csp2- Csp3-halides, are added simultaneously across variety olefins (vinyl amides, vinyl boranes, phosphonates) at room temperature in regio- enantioselective manner. The reaction, devoid sensitive organometallic reagents, takes advantage an situ generated chiral alkyl Ni(III)-intermediate to ensure stereodefined outcome Csp3–Csp2 bond-forming reaction. An (l)-(+)-isoleucine bisoxazoline ligand presence coordinating sites on alkene key for successful these "asymmetric radical relayed couplings" (ARRRCs). Further, multiple transformations amides obtained this process showcase potential new methodology straightforward assembly building blocks such as primary secondary amines oxazolines, highlighting its synthetic utility.

Language: Английский

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Nickel/Photo-Cocatalyzed Asymmetric Acyl-Carbamoylation of Alkenes

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(5), P. 2180 - 2186

Published: Jan. 23, 2020

An unprecedented asymmetric acyl-carbamoylation of pendant alkenes tethered on aryl carbamic chlorides with both aliphatic and aromatic aldehydes has been developed via the cooperative catalysis a chiral nickel-PHOX complex tetrabutylammonium decatungstate. This reaction represents first example merging hydrogen-atom-transfer photochemistry transition metal in difunctionalization alkenes. Using this protocol, variety oxindoles bearing challenging quaternary stereogenic center are furnished under mild conditions highly enantioselective manner.

Language: Английский

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Nickel‐CatalyzedDicarbofunctionalization of Alkenes^†

Chinese Journal of Chemistry, Journal Year: 2020, Volume and Issue: 38(11), P. 1371 - 1394

Published: June 16, 2020

As a straightforward strategy for rapidly increasing molecular complexity, dicarbofunctionalization of alkenes has attracted substantial interests organic synthesis, medicine chemistry, and materials science. Nickel‐catalyzed cascade dicarbofunctionalizations have been flourished in this area recently, nickel‐mediated radical pathways particularly offer new opportunities conjunctive cross‐couplings with alkyl coupling partners. Herein, we give comprehensive review nickel‐catalyzed through historical perspective, including intermolecular three‐component reactions intramolecular reactions. Among the discussed review, carbometallation/cross‐coupling process addition/cross‐coupling are two major alkenes. The oxidative cyclization 1,2‐metallate shift processes also selectively discussed. These methods overcome limitations associated using noble metals field, providing an efficient access to structurally diversified molecules.

Language: Английский

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Metal-Catalyzed Approaches toward the Oxindole Core

Accounts of Chemical Research, Journal Year: 2020, Volume and Issue: 53(8), P. 1605 - 1619

Published: July 24, 2020

ConspectusThe oxindole scaffold is a privileged structural motif that found in variety of bioactive targets and natural products. Moreover, derivatives the structure are widely present number biologically relevant compounds key intermediates synthesis diverse products pharmaceuticals. Therefore, novel methods to obtain oxindoles remain high priority synthetic organic chemistry.Over past several decades, transition-metal-catalyzed methodologies have been applied toward heterocycles. A detailed mechanistic understanding facilitates disruption traditional catalytic pathways access useful intermediates. The strategies employed generally revolved around generation high-energy organometallic intermediates, which undergo cyclization reactions through domino processes. Domino therefore attractive, as they allow facile functionalized containing all-carbon quaternary centers or tetrasubstituted olefins with chemo- stereoselectivities. Furthermore, these developed can often be easily syntheses other related scaffolds.In this Account, we discuss three unique our group has leveraged for valuable scaffolds. first section Account outlines use an initial oxidative addition C(sp2)–X bond, followed by migratory insertion, yielding neopentyl species amenable subsequent functionalizations. From reactive metal species, reported C–X reductive eliminations, anionic capture cascade reactions, intramolecular C–H functionalization second summarizes group's findings on 1,2-insertions metal–nucleophile across unsaturation, generating intermediate; tethered electrophiles form desired heterocyclic core. We explored wide array transition metal-catalyzed using approach, including rhodium-catalyzed conjugate additions, asymmetric copper-catalyzed borylcupration, palladium(II)-catalyzed chloropalladation protocol. final details dual-metal catalysis perform functionalization–allylation reaction. Throughout provide studies better enabled processes.Overall, exploiting reactivity palladium, nickel, copper, rhodium, ruthenium catalysts develop On basis utility, diversity, applicability developed, believe will prove highly important inspire further development various

Language: Английский

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Nickel‐Catalyzed Asymmetric Reductive Arylalkylation of Unactivated Alkenes

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(20), P. 6722 - 6726

Published: March 20, 2019

Abstract Reported is an asymmetric reductive dicarbofunctionalization of unactivated alkenes. Under the catalysis a Ni/BOX system, various aryl bromides, incorporating pendant olefinic unit, were successfully reacted with array primary alkyl bromides in presence Zn as reductant, furnishing series benzene‐fused cyclic compounds bearing quaternary stereocenter high enantioselectivities. Notably, this reaction avoids use pregenerated organometallics and demonstrates tolerance sensitive functionalities. The preliminary mechanistic investigations reveal that Ni‐catalyzed proceeds cascade consisting migratory insertion cross‐coupling nickel(I)‐mediated intramolecular 5‐ exo cyclization enantiodetermining step.

Language: Английский

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Recent Advances in Alkenyl sp² C–H and C–F Bond Functionalizations: Scope, Mechanism, and Applications

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(24), P. 17479 - 17646

Published: Oct. 14, 2022

Alkenes and their derivatives are featured widely in a variety of natural products, pharmaceuticals, advanced materials. Significant efforts have been made toward the development new practical methods to access this important class compounds by selectively activating alkenyl C(sp2)–H bonds recent years. In comprehensive review, we describe state-of-the-art strategies for direct functionalization sp2 C–H C–F until June 2022. Moreover, metal-free, photoredox, electrochemical also covered. For clarity, review has divided into two parts; first part focuses on currently available using different alkene as starting materials, second describes bond easily accessible gem-difluoroalkenes material. This includes scope, limitations, mechanistic studies, stereoselective control (using directing groups well metal-migration strategies), applications complex molecule synthesis where appropriate. Overall, aims document considerable advancements, current status, emerging work critically summarizing contributions researchers working fascinating area is expected stimulate novel, innovative, broadly applicable functionalizations coming

Language: Английский

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Ni-Catalyzed Ligand-Controlled Regiodivergent Reductive Dicarbofunctionalization of Alkenes

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(27), P. 10282 - 10291

Published: June 24, 2021

Transition-metal-catalyzed dicarbofunctionalization of alkenes involving intramolecular Heck cyclization followed by intermolecular cross-coupling has emerged as a powerful engine for building heterocycles with sterically congested quaternary carbon centers. However, only exo-cyclization/cross-coupling products can be obtained; endo-selective cyclization/cross-coupling not been reported yet and still poses formidable challenge. We herein report the first example catalyst-controlled regiodivergent synthesis five- six-membered benzo-fused lactams bearing all-carbon Using chiral Pyrox- or Phox-type bidentate ligand, 5-exo cyclization/cross-couplings proceed favorably to produce indole-2-ones in good yields excellent regioselectivity enantioselectivities (up 98% ee). When C6-carboxylic acid-modified 2,2′-bipyridine was used 3,4-dihydroquinolin-2-ones were obtained through 6-endo-selective processes. This transformation is modular tolerant variety functional groups. The ligand rather than substrate structures precisely dictates pattern. Moreover, synthetic value this protocol demonstrated preparation biologically relevant molecules structural scaffolds.

Language: Английский

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Nickel‐Catalyzed Asymmetric Reductive Carbo‐Carboxylation of Alkenes with CO₂

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(25), P. 14068 - 14075

Published: April 1, 2021

Abstract Reductive carboxylation of organo (pseudo)halides with CO 2 is a powerful method to provide carboxylic acids quickly. Notably, the catalytic reductive carbo‐carboxylation unsaturated hydrocarbons via fixation highly challenging but desirable approach for structurally diverse acids. There are only few reports and no examples alkenes transition metal catalysis. We report first asymmetric nickel A variety aryl (pseudo)halides, such as bromides, triflates inert chlorides particular note, undergo reaction smoothly give important oxindole‐3‐acetic acid derivatives bearing C3‐quaternary stereocenter. This transformation features mild conditions, wide substrate scope, facile scalability, good excellent chemo‐, regio‐ enantioselectivities. The highlights formal synthesis (−)‐Esermethole, (−)‐Physostigmine (−)‐Physovenine, total (−)‐Debromoflustramide B, (−)‐Debromoflustramine B (+)‐Coixspirolactam A; thereby, opening an avenue chiral natural products .

Language: Английский

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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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