Chromium‐ and Metal‐Reductant‐Free Asymmetric Nozaki–Hiyama–Kishi (NHK) Reaction Enabled by Metallaphotoredox Catalysis DOI

Pei Gu,

Linlin Ding,

Xiaowu Fang

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(37)

Published: June 25, 2024

Abstract Chiral allylic alcohols are highly prized in synthetic chemistry due to their versatile reactivity stemming from both alkenyl and hydroxyl functionalities. While the Nozaki–Hiyama–Kishi (NHK) reaction is a widely used method for synthesis of alcohols, it suffers drawbacks such as use toxic chromium salts, high amounts metal reductants, poor enantiocontrol. To address these limitations, we present novel approach involving metallaphotoredox‐catalyzed asymmetric NHK production chiral alcohols. This marries (pseudo)halides with aldehydes, leveraging synergistic blend nickel catalyst photocatalyst. innovative technique enables oxidative addition insertion just using nickel, diverging significantly conventional pathway mediated by salts. The adoption this methodology holds immense promise crafting spectrum intricate compounds, particularly those significance pharmaceuticals. Detailed experimental investigations have shed light on metallaphotoredox process, further enhancing our understanding enabling advancements.

Language: Английский

Asymmetric Cross-Coupling of Aldehydes with Diverse Carbonyl or Iminyl Compounds by Photoredox-Mediated Cobalt Catalysis DOI

Zhiyong Chi,

Jia-Bin Liao,

Xiuliang Cheng

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(15), P. 10857 - 10867

Published: April 8, 2024

The asymmetric cross-coupling of unsaturated bonds, hampered by their comparable polarity and reactivity, as well the scarcity efficient catalytic systems capable diastereo- enantiocontrol, presents a significant hurdle in organic synthesis. In this study, we introduce highly adaptable photochemical cobalt catalysis framework that facilitates chemo- stereoselective reductive cross-couplings between common aldehydes with broad array carbonyl iminyl compounds, including N-acylhydrazones, aryl ketones, aldehydes, α-keto esters. Our methodology hinges on synergistic mechanism driven photoredox-induced single-electron reduction subsequent radical–radical coupling, all precisely guided chiral catalyst. Various optically enriched β-amino alcohols unsymmetrical 1,2-diol derivatives (80 examples) have been synthesized good yields (up to 90% yield) high stereoselectivities >20:1 dr, 99% ee). Of particular note, approach accomplishes unattainable transformations disparate partners without reliance any external photosensitizer, thereby further emphasizing its versatility cost-efficiency.

Language: Английский

Citations

17
Desymmetrization–Addition Reaction of Cyclopropenes to Imines via Synergistic Photoredox and Cobalt Catalysis DOI

Xiang‐Kui He,

Liang‐Qiu Lu,

Bao-Ru Yuan

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(28), P. 18892 - 18898

Published: July 5, 2024

Herein, we designed a reaction for the desymmetrization-addition of cyclopropenes to imines by leveraging synergy between photoredox and asymmetric cobalt catalysis. This protocol facilitated synthesis series chiral functionalized cyclopropanes with high yield, enantioselectivity, diastereoselectivity (44 examples, up 93% yield >99% ee). A possible mechanism involving cyclopropene desymmetrization Co-H species imine addition Co-alkyl was proposed. study provides novel route important extends frontier metallaphotoredox

Language: Английский

Citations

17
Nickel-Catalyzed Enantioselective Reductive Arylation of Common Ketones DOI
Shuai Huang, Jianrong Steve Zhou

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(19), P. 12895 - 12900

Published: May 2, 2024

A nickel complex of chiral bisoxazolines catalyzed the stereoselective reductive arylation ketones in high enantioselectivity. range common acyclic and cyclic reacted without aid directing groups. Mechanistic studies using isolated a bis(oxazoline) (L)Ni(Ar)Br revealed that Mn reduction was not needed, while Lewis acidic titanium alkoxides were critical to ketone insertion.

Language: Английский

Citations

11
Chromium‐ and Metal‐Reductant‐Free Asymmetric Nozaki–Hiyama–Kishi (NHK) Reaction Enabled by Metallaphotoredox Catalysis DOI

Pei Gu,

Linlin Ding,

Xiaowu Fang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(37)

Published: June 25, 2024

Abstract Chiral allylic alcohols are highly prized in synthetic chemistry due to their versatile reactivity stemming from both alkenyl and hydroxyl functionalities. While the Nozaki–Hiyama–Kishi (NHK) reaction is a widely used method for synthesis of alcohols, it suffers drawbacks such as use toxic chromium salts, high amounts metal reductants, poor enantiocontrol. To address these limitations, we present novel approach involving metallaphotoredox‐catalyzed asymmetric NHK production chiral alcohols. This marries (pseudo)halides with aldehydes, leveraging synergistic blend nickel catalyst photocatalyst. innovative technique enables oxidative addition insertion just using nickel, diverging significantly conventional pathway mediated by salts. The adoption this methodology holds immense promise crafting spectrum intricate compounds, particularly those significance pharmaceuticals. Detailed experimental investigations have shed light on metallaphotoredox process, further enhancing our understanding enabling advancements.

Language: Английский

Citations

5
CoH-catalyzed asymmetric remote hydroalkylation of heterocyclic alkenes: a rapid approach to chiral five-membered S- and O-heterocycles DOI Creative Commons
Lingzi Zhao,

Feipeng Liu,

Yan Zhuang

et al.

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

Citations

4
Research Progress in the Synthesis of α-Tertiary Amines via Radical Strategies DOI

Jia‐Heng Fang,

Run Tian,

Ji‐Jun Chen

et al.

Chinese Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 45(1), P. 22 - 22

Published: Jan. 1, 2025

Language: Английский

Citations

0
Asymmetric reductive arylation and alkenylation to access S-chirogenic sulfinamides DOI Creative Commons

Xiaowu Fang,

Longlong Xi, Minyan Wang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 15, 2025

The study of the stereochemistry organic sulfur compounds has been ongoing for over a century, with S-chirogenic pharmacophores playing an essential role in drug discovery within bioscience and medicinal chemistry. Traditionally, synthesis sulfinamides featuring stereogenic sulfur(IV) centers involves complex, multistep process that often depends on chiral auxiliaries or kinetic resolution. Here, we introduce effective versatile method synthesizing diverse classes through selective aryl alkenyl addition to sulfinylamines. This is catalysed by nickel cobalt complex under reductive conditions, eliminating need preformed organometallic reagents. facilitates incorporation array halides at position, enabling their integration into various biologically significant pharmacophores. Our detailed mechanistic investigations density functional theory calculations provide insights reaction pathway, particularly highlighting enantiocontrol mode during process. play authors report methodology asymmetric sulfinylamines via common-Earth-metal catalysis.

Language: Английский

Citations

0
Regio- and Enantioselective Hydromethylation of 3-Pyrrolines and Glycals Enabled by Cobalt Catalysis DOI Creative Commons

Mengyang Shen,

C. NIU,

Xuchao Wang

et al.

JACS Au, Journal Year: 2024, Volume and Issue: 4(6), P. 2312 - 2322

Published: June 11, 2024

Enantioenriched 3-methylpyrrolidine, with its unique chiral nitrogen-containing core skeleton, exists widely in various functional molecules, including natural products, bioactive compounds, and pharmaceuticals. Traditional methods for synthesizing these valuable methyl-substituted heterocycles often involve enzymatic processes or complex procedures auxiliaries, limiting the substrate scope efficiency. Efficient catalytic methylation, especially an enantioselective manner, has been a long-standing challenge chemical synthesis. Herein, we present novel approach remote stereoselective installation of methyl group onto N-heterocycles, leveraging CoH-catalyzed asymmetric hydromethylation strategy. By effectively combining commercial cobalt precursor modified bisoxazoline (BOX) ligand, variety easily accessible 3-pyrrolines can be converted to enantiopure 3-(isotopic labeling)methylpyrrolidine compounds outstanding enantioselectivity. This efficient protocol streamlines two-step synthesis enantioenriched which previously required up five six steps under harsh conditions expensive starting materials.

Language: Английский

Citations

3
Cobalt-Catalyzed Enantioselective Reductive Arylation, Heteroarylation, and Alkenylation of Michael Acceptors via an Elementary Mechanism of 1,4-Addition DOI
Mengxin Zhao, Wenqiang Xu, Yun‐Dong Wu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(29), P. 20477 - 20493

Published: July 10, 2024

Cobalt complexes with chiral quinox ligands effectively promote the enantioselective conjugate addition of enones using aryl, heteroaryl, and alkenyl halides sulfonates. Additionally, a cobalt complex strongly donating diphosphine, BenzP*, successfully catalyzes asymmetric reductive arylation alkenylation α,β-unsaturated amides. Both catalytic systems show broad scopes tolerance sensitive functional groups. reactions can be scaled up low loadings catalysts. Experimental results density theory (DFT) calculations suggest new mechanism elementary 1,4-addition aryl cobalt(I) complexes.

Language: Английский

Citations

3
A General Enantioselective α-Alkyl Amino Acid Derivatives Synthesis Enabled by Cobalt-Catalyzed Reductive Addition DOI

Chengxi Zhang,

Xianqing Wu, Jingping Qü

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 12, 2024

Enantioenriched unnatural amino acids represent a prevalent motif in organic chemistry, with profound applications biochemistry, medicinal and materials science. Herein, we report cobalt-catalyzed aza-Barbier reaction of dehydroglycines unactivated alkyl halides to afford α-amino esters high enantioselectivity. This catalytic reductive alkylative addition protocol circumvents the use moisture-, air-sensitive organometallic reagents, stoichiometric chiral auxiliaries, enabling conversion variety primary, secondary, even tertiary α-alkyl-amino under mild conditions, thus leading broad functional group tolerance. The expedient access biologically active motifs demonstrates practicality this by reducing number synthetic steps enhancing efficiency.

Language: Английский

Citations

3