Direct Enantioselective C(sp³)–H Acylation for the Synthesis of α-Amino Ketones

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(45), С. 19058 - 19064

Опубликована: Окт. 30, 2020

A direct enantioselective acylation of α-amino C(sp3)-H bonds with carboxylic acids has been achieved via the merger transition metal and photoredox catalysis. This straightforward protocol enables cross-coupling a wide range acids, one class feedstock chemicals, readily available N-alkyl benzamides to produce highly valuable ketones in high enantioselectivities under mild conditions. The synthetic utility this method is further demonstrated by gram scale synthesis application late-stage functionalization. provides an unprecedented solution address challenging stereocontrol metallaphotoredox catalysis Mechanistic studies suggest α-C(sp3)-H bond benzamide coupling partner cleavage photocatalytically generated bromine radicals form alkyl radicals, which subsequently engages nickel-catalyzed asymmetric acylation.

Язык: Английский

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

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(25), С. 14068 - 14075

Опубликована: Апрель 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 .

Язык: Английский

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

Chemical Reviews, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 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

Язык: Английский

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Cobalt‐Catalyzed Asymmetric Aza‐Nozaki–Hiyama–Kishi (NHK) Reaction of α‐Imino Esters with Alkenyl Halides

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(7)

Опубликована: Янв. 2, 2024

Chromium-catalyzed enantioselective Nozaki-Hiyama-Kishi (NHK) reaction represents one of the most powerful approaches for formation chiral carbon-heteroatom bond. However, construction sterically encumbered tetrasubstituted stereocenter through NHK still posts a significant challenge. Herein, we disclose cobalt-catalyzed aza-NHK ketimine with alkenyl halide to provide convenient synthetic approach manufacture enantioenriched α-vinylic amino acid. This protocol exhibits excellent functional group tolerance 99 % ee in cases. Additionally, this asymmetric reductive method is also applicable aldimine access trisubstituted stereogenic centers.

Язык: Английский

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Nickel-Catalyzed Multicomponent Coupling: Synthesis of α-Chiral Ketones by Reductive Hydrocarbonylation of Alkenes

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(35), С. 14089 - 14096

Опубликована: Авг. 26, 2021

A nickel-catalyzed, multicomponent regio- and enantioselective coupling via sequential hydroformylation carbonylation from readily available starting materials has been developed. This modular hydrofunctionalization strategy enables the straightforward reductive hydrocarbonylation of a broad range unactivated alkenes to produce wide variety unsymmetrical dialkyl ketones bearing functionalized α-stereocenter, including enantioenriched chiral α-aryl α-amino ketones. It uses bisoxazoline as ligand, silane reductant, chloroformate safe CO source, racemic secondary benzyl chloride or an N-hydroxyphthalimide (NHP) ester protected acid alkylation reagent. The benign nature this process renders method suitable for late-stage functionalization complex molecules.

Язык: Английский

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

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(33), С. 12961 - 12967

Опубликована: Авг. 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.

Язык: Английский

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Catalytic Desymmetric Dicarbofunctionalization of Unactivated Alkenes

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(26)

Опубликована: Март 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.

Язык: Английский

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Nickel-Catalyzed Three-Component Alkylacylation of Alkenes Enabled by a Photoactive Electron Donor–Acceptor Complex

Organic Letters, Год журнала: 2022, Номер 24(22), С. 3938 - 3943

Опубликована: Май 23, 2022

An electron donor-acceptor complex-enabled, nickel-catalyzed three-component net-reductive 1,2-alkylacylation of alkenes is developed. This conjunctive reductive acyl cross-coupling process obviates the use an exogenous photocatalyst and a stoichiometric metal-based reductant, affording various synthetically useful 1,3-dicarbonyl compounds in good yields with broad substrate scope excellent functional group tolerance. Both alkyl electrophiles are derived from highly abundant readily accessible carboxylic acids, making catalytic 1,2-dicarbofunctionalization more general sustainable.

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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