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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Divergent Access to Chiral C2- and C3-Alkylated Pyrrolidines by Catalyst-Tuned Regio- and Enantioselective C(sp³)–C(sp³) Coupling

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(28), P. 15456 - 15464

Published: June 12, 2023

Novel-substituted pyrrolidine derivatives are widely used in drugs and bioactive molecules. The efficient synthesis of these valuable skeletons, especially enantiopure derivatives, is still recognized as a key bottleneck to overcome chemical synthesis. Herein, we report highly catalyst-tuned regio- enantioselective hydroalkylation reaction for the divergent chiral C2- C3-alkylated pyrrolidines through desymmetrization readily available 3-pyrrolines. catalytic system consists CoBr2 with modified bisoxazoline (BOX) ligand, which can achieve asymmetric C(sp3)-C(sp3) coupling via distal stereocontrol, providing series high efficiency. Moreover, nickel allows synthesize C2-alkylated tandem alkene isomerization/hydroalkylation reaction. This method uses catalysts, BOX ligands, reagents, delivering enantioenriched 2-/3-alkyl substituted excellent enantioselectivity (up 97% ee). We also demonstrate compatibility this transformation complex substrates derived from molecules good efficiency, offers distinct entry more functionalized N-heterocycles.

Language: Английский

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Hydrogen Source Tuned Regiodivergent Asymmetric Hydroalkylations of 2‐Substituted 1,3‐Dienes with Aldehydes by Cobalt‐Catalysis

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(23)

Published: April 3, 2024

Abstract Catalytic methods allowing for the reliable prediction and control of diverse regioselectivity along with enantioselectivity to access different regio‐ enantiomers by switching least reaction parameters are one most attractive ways in organic synthesis, which provide enantioenriched architectures from identical starting materials. Herein, a Co‐catalyzed regiodivergent enantioselective reductive hydroalkylation 1,3‐dienes aldehydes has been achieved, furnishing homoallylic alcohol good levels enantioselectivity. The features switch tuned selection proton source. use an acid as source provided asymmetric 1,2‐hydroalkylation products under conditions, yet 4,3‐hydroalkylation were obtained silane hydride This catalytic protocol allows alcohols two continuous saturated carbon centers regio‐, diastereo‐,

Language: Английский

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Enantioselective Access to β-Amino Carbonyls via Ni-Catalyzed Formal Olefin Hydroamidation

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(21), P. 14745 - 14753

Published: May 14, 2024

We herein describe a Ni-catalyzed formal hydroamidation of readily available α,β-unsaturated carbonyl compounds to afford valuable chiral β-amino acid derivatives (up >99:1 e.r.) using dioxazolones as robust amino source. A wide range alkyl-substituted olefins conjugated esters, amides, thioesters, and ketones were successfully amidated at the β-position with excellent enantioselectivity for first time. Combined experimental computational mechanistic studies supported our working hypothesis that this unconventional β-amidation unsaturated substrates can be attributed polar-matched migratory olefin insertion an (amido)(Cl)Ni

Language: Английский

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Silanes as a versatile hydride source for Ni–H catalysis: a promising tool for π-hydro functionalization

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(15), P. 4290 - 4317

Published: Jan. 1, 2024

Nickel-catalyzed hydrofunctionalization of π-substrates is a possibly effective method to synthesize several value-added molecular architectures. This review covers the NiH catalyzed reactions alkenes, alkynes and allenes.

Language: Английский

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NiH-catalyzed C–N bond formation: insights and advancements in hydroamination of unsaturated hydrocarbons

Chemical Science, Journal Year: 2023, Volume and Issue: 15(2), P. 442 - 457

Published: Dec. 6, 2023

The formation of C-N bonds is a fundamental aspect organic synthesis, and hydroamination has emerged as pivotal strategy for the synthesis essential amine derivatives. In recent years, there been surge interest in metal hydride-catalyzed reactions common alkenes alkynes. This method avoids need stoichiometric organometallic reagents overcomes problems associated with specific compounds that may impact functional group compatibility. Notably, developments have brought to forefront olefinic hydroamidation facilitated by nickel hydride (NiH) catalysis. inclusion suitable chiral ligands paved way realization asymmetric realm olefins. review aims provide an in-depth exploration latest achievements bond through intermolecular catalyzed hydrides. Leveraging this innovative approach, diverse range alkene alkyne substrates can be efficiently transformed into value-added enriched bonds. intricacies are succinctly elucidated, offering concise overview underlying reaction mechanisms. It our aspiration comprehensive will stimulate further progress NiH-catalytic techniques, fine-tune systems, drive innovation catalyst design, foster deeper understanding

Language: Английский

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Regiodivergent and Enantioselective Synthesis of Cyclic Sulfones via Ligand‐Controlled Nickel‐Catalyzed Hydroalkylation

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(29)

Published: April 29, 2024

Abstract Cyclic sulfones have demonstrated important applications in drug discovery. However, the catalytic and enantioselective synthesis of chiral cyclic remains challenging. Herein, we develop nickel‐catalyzed regiodivergent hydroalkylation sulfolenes to streamline alkyl sulfones. The method has broad scope high functional group tolerance. regioselectivity can be controlled by ligands only. A neutral PYROX ligand favors C3‐alkylation whereas an anionic BOX C2‐alkylation. This control is kinetic origin as C2‐bound Ni intermediates are always thermodynamically more stable. Reactivity study a wide range relevant reveal I /Ni III cycle with II −H species resting state. regio‐ enantio‐determining step insertion this into 2‐sulfolene. work provides efficient for class organic compounds enhances mechanistic understanding Ni‐catalyzed stereoselective hydroalkylation.

Language: Английский

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CoH-catalyzed asymmetric remote hydroalkylation of heterocyclic alkenes: a rapid approach to chiral five-membered S- and O-heterocycles

Chemical Science, Journal Year: 2024, Volume and Issue: 15(23), P. 8888 - 8895

Published: Jan. 1, 2024

A highly efficient method achieves precise construction of alkyl chiral centers at remote C3-positions in five-membered S/O-heterocycles via cobalt-catalyzed asymmetric hydroalkylation heterocyclic alkenes.

Language: Английский

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Nickel Catalyzed Enantioselective 1,4-Hydroamination of 1,3-Dienes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(27), P. 18440 - 18450

Published: July 1, 2024

Transition metal-catalyzed enantioselective hydroamination of 1,3-dienes provides a direct methodology for the construction chiral allylamines. So far, all reported examples used nucleophilic amines and proceeded with 3,4-regioselectivity. Herein, we describe first example nickel-catalyzed 1,4-hydroamination using trimethoxysilane hydroxylamines structurally adaptable aromatic spiroketal based diphosphine (SKP) as ligand, affording wide array α-substituted allylamines in high yields excellent regio- enantioselectivities. This operationally simple protocol demonstrated broad substrate scope functional group compatibility, significantly expanding chemical space Experimental DFT studies were performed to elucidate mechanism rationalize enantioselectivities reaction.

Language: Английский

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Synthesis of α‐N‐Heteroaryl Ketones by Nickel‐Catalyzed Chemo‐, Regio‐ and Enantioselective Carbonylation of Alkenes and N‐Alkenyl Heteroarenes

Angewandte Chemie International Edition, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Enantioenriched α-aminoketones serve as important substructures in life science and precursors for the synthesis of diverse value-added targets organic biochemistry. However, direct access to enantioenriched from simple readily available starting materials remains a formidable challenge. Herein, we report an unprecedented nickel-catalyzed asymmetric cross-coupling protocol α-N-heteroaryl ketones alkenes enamines presence carbon monoxide surrogate. The success this reaction relies on sorting two different along with control regio- enantioselectivity. This reductive-oxidative carbonylation unactivated featuring use surrogate allows gas-free streamlined assembly distinct alkenes.

Language: Английский

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