Electroreduction Enables Regioselective 1,2‐Diarylation of Alkenes with Two Electrophiles

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(17)

Published: Feb. 24, 2023

Precisely introducing two similar functional groups into bulk chemical alkenes represents a formidable route to complex molecules. Especially, the selective activation of electrophiles is in crucial demand, yet challenging for cross-electrophile-coupling. Herein, we demonstrate redox-mediated electrolysis, which aryl nitriles are both radical precursors and redox-mediators, enables an intermolecular alkene 1,2-diarylation with remarkable regioselectivity, thereby avoiding involvement transition-metal catalysts. This transformation utilizes cyanoarene anions activating various halides (including iodides, bromides, even chlorides) affords adducts up 83 % yield >20 : 1 regioselectivity more than 80 examples, providing feasible approach bibenzyl derivatives.

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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Photoinduced Regiodivergent and Enantioselective Cross-Coupling of Glycine Derivatives with Hydrocarbon Feedstocks

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Regiodivergent asymmetric synthesis represents a transformative strategy for the efficient generation of structurally diverse chiral products from single set starting materials, significantly enriching their enantiomeric composition. However, design radical-mediated regiodivergent and enantioselective reactions that can accommodate wide range functional groups substrates has posed significant challenges. The obstacles primarily lie in switching regioselectivity achieving high enantiodiscrimination, especially when dealing with high-energy intermediates. To address these issues, we have developed new catalytic system integrates photoinduced hydrogen atom transfer (HAT) copper catalysis, involving fine-tuning ligands, additives, other reaction parameters. facilitates cross-couplings between N-aryl glycine ester/amide derivatives abundant hydrocarbon feedstocks through strong C(sp3)–H bond activation. This approach allows controlled stereoselective formation C(sp3)–C(sp3) C(sp3)–N bonds, yielding rich variety C- or N-alkylated esters amides commendable yields (up to 92% yield), exclusive regioselectivities (typically >20:1 rr), enantioselectivities 96% ee). Our methodology not only provides promising avenue incorporation alkyl functionalities onto specific sites biologically molecules but also offers practical while simultaneously induction within photochemical reactions.

Language: Английский

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Three-Component Asymmetric Ni-Catalyzed 1,2-Dicarbofunctionalization of Unactivated Alkenes via Stereoselective Migratory Insertion

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(42), P. 19337 - 19343

Published: Oct. 12, 2022

An asymmetric 1,2-dicarbofunctionalization of unactivated alkenes with aryl iodides and aryl/alkenylboronic esters under nickel/bioxazoline catalysis is disclosed. A wide array alkenyl nucleophiles are tolerated, furnishing the products in good yield high enantioselectivity. In addition to terminal alkenes, 1,2-disubstituted internal participate reaction, establishing two contiguous stereocenters diastereoselectivity moderate combination experimental computational techniques shed light on mechanism catalytic transformation, pointing a closed-shell pathway an enantiodetermining migratory insertion step, where stereoinduction arises from synergistic interactions between sterically bulky achiral sulfonamide directing group hemilabile bidentate ligand.

Language: Английский

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Directed Asymmetric Nickel‐Catalyzed Reductive 1,2‐Diarylation of Electronically Unactivated Alkenes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(13)

Published: Jan. 31, 2023

Transition-metal catalyzed intermolecular 1,2-diarylation of electronically unactivated alkenes has emerged as an extensive research topic in organic synthesis. However, most examples are mainly limited to terminal alkenes. Furthermore, transition-metal asymmetric still remains unsolved and is a formidable challenge. Herein, we describe highly efficient directed nickel-catalyzed reductive internal with high diastereoselectivities. More importantly, our further effort towards enantioselective the challenging achieved, furnishing various polyarylalkanes featuring benzylic stereocenters yields good enantioselectivities Interestingly, generation cationic Ni-catalyst by adding alkali metal fluoride key increased efficiency this reaction.

Language: Английский

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Enantioselective C–C cross-coupling of unactivated alkenes

Nature Catalysis, Journal Year: 2023, Volume and Issue: 6(11), P. 1087 - 1097

Published: Oct. 5, 2023

Language: Английский

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

Synthesis, Journal Year: 2023, Volume and Issue: 56(01), P. 1 - 15

Published: June 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

Language: Английский

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Palladium-Catalyzed Divergent Enantioselective Functionalization of Cyclobutenes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(18), P. 12691 - 12701

Published: April 27, 2024

Aliphatic strained rings have been increasingly applied in medicinal chemistry due to their beneficial physicochemical and pharmacokinetic properties. However, the divergent synthesis of enantioenriched cyclobutane derivatives with various structural patterns continues be a significant challenge. Here, we disclose palladium-catalyzed enantioselective desymmetrization cyclobutenes, resulting series hydroarylation 1,2- 1,3-diarylation products via interceptions common Heck intermediate. Mechanistic investigations provide valuable insights into understanding catalytic mode palladium catalysts observed variations deuterium-responsive behavior during reactions. Furthermore, synthetic utility is demonstrated syntheses deuterated drug candidate belaperidone skeletons pseudosymmetrical truxinic acid-type derivatives.

Language: Английский

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Palladium-Catalyzed Enantioselective Multicomponent Cross-Coupling of Trisubstituted Olefins

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(24), P. 16892 - 16901

Published: June 6, 2024

The development of a catalytic method for stereogenic carbon center formation holds immense significance in organic synthesis. Transition-metal-catalyzed cross-coupling reaction has been regarded as straightforward and efficient tool stereoselectively forging C–C bond. Nevertheless, the creation acyclic all-carbon quaternary-containing vicinal stereocenters remains notoriously challenging within domain chemistry despite their prominence various bioactive small molecules. Herein, we describe palladium-catalyzed asymmetric multicomponent trisubstituted alkene with aryl diazonium salts arylboronic acids to realize tertiary-quaternary centers high regio-, distereo-, enantioselectivity. Specifically, precise manipulation stereoconfiguration alkenes enables divergent stereoselective reaction, thus allowing facile construction all four enantiomers. Harnessing ligand-swap strategy involving chiral bisoxazoline an achiral fumarate individually accelerates enantioselective migratory insertion reductive elimination step process, supported by density functional theory (DFT) calculations, obviating requirement neighboring directing group internal olefin skeleton.

Language: Английский

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Remote Stereocenter through Amide-Directed, Rhodium-Catalyzed Enantioselective Hydroboration of Unactivated Internal Alkenes

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(29), P. 13071 - 13078

Published: July 13, 2022

Despite the frequent occurrence of γ-branched amines in bioactive molecules, direct catalytic asymmetric synthesis this structural motif containing a remote stereocenter remains an important synthetic challenge. Here, we report amide-directed, rhodium-catalyzed highly diastereo- and enantioselective hydroboration unactivated internal alkenes. This method provided facile access to enantioenriched β,γ-vicinal stereocenters. The application strategy molecules was demonstrated. Computational studies indicated that migratory insertion alkene into rhodium hydride controls enantioselectivity.

Language: Английский

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