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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Metal‐Free SF₆Activation: A New SF₅‐Based Reagent Enables Deoxyfluorination and Pentafluorosulfanylation Reactions

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(27)

Опубликована: Апрель 26, 2022

The activation of SF6 , a potent greenhouse gas, under metal-free and visible light conditions is reported. Herein, mechanistic investigations including EPR spectroscopy, NMR studies cyclic voltammetry allowed the rational design new fluorinating reagent which was synthesized from 2-electron with commercially available TDAE. This SF5 -based efficiently employed for deoxyfluorination CO2 fluorinative desulfurization CS2 allowing formation useful fluorinated amines. Moreover, first time we demonstrated that our could afford mild generation Cl-SF5 gas. finding exploited chloro-pentafluorosulfanylation alkynes alkenes.

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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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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O-Allylhydroxyamine: A Bifunctional Olefin for Construction of Axially and Centrally Chiral Amino Alcohols via Asymmetric Carboamidation

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(14), С. 8150 - 8162

Опубликована: Апрель 4, 2023

Difunctionalization of olefins offers an attractive approach to access complex chiral structures. Reported herein is the design N-protected O-allylhydroxyamines as bifunctional that undergo catalytic asymmetric 1,2-carboamidation with three classes (hetero)arenes afford amino alcohols via C-H activation. The C═C bond in O-allylhydroxyamine activated by intramolecular electrophilic amidating moiety well a migrating directing group. carboamidation reaction pattern depends on nature (hetero)arene reagent. Simple achiral reacted give centrally β-amino excellent enantioselectivity. employment axially prochiral or racemic heteroarenes afforded both axial and central chirality enantio- diastereoselectivity. In case heteroarenes, coupling follows kinetic resolution s-factor up >600. A nitrene-based mechanism has been suggested based experimental studies, unique mode induction diastereoselectivity proposed. Applications alcohol products have demonstrated.

Язык: Английский

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BF₃-Catalyzed Intramolecular Fluorocarbamoylation of Alkynes via Halide Recycling

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(20), С. 11012 - 11018

Опубликована: Май 12, 2023

A BF3-catalyzed atom-economical fluorocarbamoylation reaction of alkyne-tethered carbamoyl fluorides is reported. The catalyst acts as both a fluoride source and Lewis acid activator, thereby enabling the formal insertion alkynes into strong C-F bonds through halide recycling mechanism. developed method provides access to 3-(fluoromethylene) oxindoles γ-lactams with excellent stereoselectivity, including fluorinated derivatives known protein kinase inhibitors. Experimental computational studies support stepwise mechanism for involving turnover-limiting cyclization step, followed by internal transfer from BF3-coordinated adduct. For methylene oxindoles, thermodynamically driven Z-E isomerization facilitated transition state aromatic character. In contrast, this stabilization not relevant γ-lactams, which results in higher barrier exclusive formation Z-isomer.

Язык: Английский

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Ni- and Pd-Catalyzed Enantioselective 1,2-Dicarbofunctionalization of Alkenes

Synthesis, Год журнала: 2023, Номер 56(01), С. 1 - 15

Опубликована: Июнь 12, 2023

Abstract Catalytic enantioselective 1,2-dicarbofunctionalization (1,2-DCF) of alkenes is a powerful transformation growing importance in organic synthesis for constructing chiral building blocks, bioactive molecules, and agrochemicals. Both two- three-component context, this family reactions generates densely functionalized, structurally complex products single step. Across several distinct mechanistic pathways at play these transformations with nickel or palladium catalysts, stereocontrol can be obtained through tailored ligands. In Review we discuss the various strategies, mechanisms, catalysts that have been applied to achieve enantioinduction alkene 1,2-DCF. 1 Introduction 2 Two-Component Enantioselective 1,2-DCF via Migratory Insertion 3 Radical Capture 4 Three-Component 5 6 Miscellaneous Mechanisms 7 Conclusion

Язык: Английский

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Three-Component Visible-Light-Induced Palladium-Catalyzed 1,2-Alkyl Carbamoylation/Cyanation of Alkenes

ACS Catalysis, Год журнала: 2021, Номер 11(21), С. 13217 - 13222

Опубликована: Окт. 15, 2021

A mild visible-light-induced Pd-catalyzed one-pot three-component alkyl-carbamoylation and cyanation of alkenes was developed. This general transformation, which proceeds via the in situ formation a reactive ketenimine intermediate, allows for rapid construction broad range valuable amides nitriles from readily available alkenes, alkyl iodides, isocyanides. An efficient synthesis tetrazole amidine this approach also demonstrated.

Язык: Английский

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Nickel‐Catalyzed Enantioselective Reductive Alkyl‐Carbamoylation of Internal Alkenes

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(36)

Опубликована: Июль 12, 2022

Herein, we leverage the Ni-catalyzed enantioselective reductive dicarbofunctionalization of internal alkenes with alkyl iodides to enable synthesis chiral pyrrolidinones bearing vicinal stereogenic centers. The application newly developed

Язык: Английский

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