A modular approach to catalytic stereoselective synthesis of chiral 1,2-diols and 1,3-diols

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

Published: Jan. 3, 2025

Optically pure 1,2-diols and 1,3-diols are the most privileged structural motifs, widely present in natural products, pharmaceuticals chiral auxiliaries or ligands. However, their synthesis relies on use of toxic expensive metal catalysts suffer from low regioselectivity. Catalytic asymmetric optically 1,n-diols bulk chemicals a highly stereoselective atom-economical manner remains formidable challenge. Here, we disclose versatile modular method for enantioenriched high-production-volume ethane-1,2-diol (MEG) 1,3-propanediol (PDO), respectively. The key to success is temporarily mask diol group as an acetonide, which imparts selectivity step C(sp3)-H functionalization. Additionally, containing two stereogenic centers also prepared through diastereoselective late-stage functionalization biological active compounds expedient ligands pharmaceutically relevant molecules further highlight synthetic potential this protocol. authors report ethylene glycol 1,3-propanediol,

Language: Английский

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Nickel-Catalyzed and Tetrahydroxydiboron-Mediated Allylation of Aldehydes with Allyl Alcohols

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

The allylation of carbonyl compounds to form homoallylic alcohols represents one the significant synthetic transformations. In this letter, we describe a new method for aldehydes with allyl facilitated by nickel chloride and tetrahydroxydiboron. This approach offers mild straightforward procedure synthesis from ketones.

Language: Английский

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Nickel-catalyzed reductive alkynylation of ketoimines via unstrained C–C bond activation

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 111050 - 111050

Published: March 1, 2025

Language: Английский

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Catalyst-controlled regiodivergence and stereodivergence in formal cross-[4+2] cycloadditions: The unique effect of bismuth(III)

Science Advances, Journal Year: 2025, Volume and Issue: 11(13)

Published: March 26, 2025

The [4+2] cycloaddition is crucial for constructing six-membered rings in pharmaceuticals and natural products. Cross-[4+2] cycloadditions offer greater product diversity than traditional diene-dienophile reactions due to multiple possible pathways. However, precise control over regio- stereoselectivity various isomers remains a great challenge. This study reports catalyst-controlled regiodivergent formal cross-cycloadditions of acyclic dienes enones, significantly enhancing access diverse pyrazole-fused spirooxindoles. Chiral phosphoric acid (CPA) catalysis enables endoselective cycloadditions, while Bi(III) with CPA ligand yields [2+4] products high stereoselectivity. A Claisen rearrangement the adduct produces exo-selective product, further increasing stereochemical enabling synthesis six stereo-isomers from single substrate set. DFT calculations reveal that reverses regioselectivity by repositioning reactants pocket stabilizing enone oxygen’s negative charge. In addition, 3as demonstrates therapeutic potential against triple-negative breast cancer, an IC 50 8.5 μM MDA-MB-453 cells.

Language: Английский

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Transfer Learning-Enabled Ligand Prediction for Ni-Catalyzed Atroposelective Suzuki–Miyaura Cross-Coupling Based on Mechanistic Similarity: Leveraging Pd Knowledge for Ni Discovery

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

Published: March 28, 2025

The rational design of novel molecular catalysts often confronts challenges due to complex structure–performance relationships. Emerging data-driven approaches provide revolutionary solutions, yet the application machine learning new catalyst development inevitably faces a low-data regime with limited effective modelings available. In this study, we present transfer strategy facilitate knowledge from well-documented Pd catalysis novel, underexplored Ni system. By synergistically modeling extensive data Ni/Sadphos data, our approach accurately predicted Sadphos ligands, enabling first atroposelective Ni-catalyzed Suzuki–Miyaura cross-coupling reaction. synthetic utility learning-predicted ligand was further demonstrated in its broad scope, gram-scale synthesis, and precise control dual axial chiralities ternaphthalene through sequential coupling under catalysis. Additionally, density functional theory calculations were employed reveal reaction mechanism stereochemical model catalyst, validating proposed mechanistic connection between Pd. This work demonstrates how models can effectively leverage connectivity, applying relationship literature predict catalysts, providing for few-shot perspective.

Language: Английский

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Ligand Controlled Stereodivergent Construction of 1,3-Nonadjacent Stereocenters via Nickel-Catalyzed Reductive Cyclization/Cross-Couplings

Wuhan University Journal of Natural Sciences, Journal Year: 2024, Volume and Issue: 29(3), P. 195 - 197

Published: June 1, 2024

Molecules with multiple stereocenters are widely present in biologically active natural products and pharmaceuticals.These molecules exhibit great three-dimensional structural diversity, which can affect the strength selectivity of protein-ligand interactions [1] .Therefore, precise synthesis each stereoisomer is very important medicinal chemistry.In past 40 years, asymmetric catalysis has developed rapidly, a variety methods been to construct chiral compounds containing single or adjacent [2] .However, there few reports on simultaneous construction 1, 3-nonadjacent highly stereoselective manner, especially acyclic [3] (Fig. 1(a)).In addition, for stereodivergent all possible stereoisomers product, most studies date focused dual-catalyst systems, while it reamins extremely challenging achieve such transformations using catalyst by adjusting ligand [4] .The Kong group focusing nickel-catalyzed reductive cyclization difunctionalization alkenes efficiently heterocycles all-carbon quaternary stereocenters.This transformation attracted widespread attention due its advantages cases where C(sp 3 ) electrophiles unstable require steps prepare [5] .Although have explored, constructing 1,3-nonadjacent secondary alkyl not remain formidable challenge.

Language: Английский

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Visible light induced cooperative catalysis by 4CzIPN and Mg(NO3)2·6H2O to furnish C-P functionalization of alkenes and indoles

Journal of Catalysis, Journal Year: 2024, Volume and Issue: 438, P. 115710 - 115710

Published: Aug. 18, 2024

Language: Английский

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Ni‐Catalyzed Enantioselective Reductive Cyclization/Amidation and Amination of 1,6‐Enynes and 1,7‐Enynes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 64(1)

Published: Aug. 28, 2024

Transition-metal-catalyzed hydroamination of unsaturated hydrocarbons is an appealing synthetic tool for the construction high value-added chiral amines. Despite significant progress in asymmetric alkenes, allenes, and 1,3-dienes, 1,6-enynes or 1,7-enynes remains rather limited due to enormous challenges controlling chemoselectivity stereoselectivity reaction. Herein, we report a Ni-catalyzed chemo- enantioselective reductive cyclization/amidation amination using dioxazolones anthranils as nitrene-transfer reagents. This mild, modular, practical protocol provides rapid access variety enantioenriched 2-pyrrolidone 2-piperidone derivatives bearing aminomethylene group at 4-position good yields (up 83 %) with excellent enantioselectivities (46 examples, up 99 % ee). Mechanistic experiments density functional theory calculations indicate that reaction initiated by hydronickelation alkynes followed migratory insertion into than [2+2+1] oxidative addition process nickel alkenes alkynes.

Language: Английский

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Ni‐Catalyzed Enantioselective Reductive Cyclization/Amidation and Amination of 1,6‐Enynes and 1,7‐Enynes

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 137(1)

Published: Aug. 28, 2024

Abstract Transition‐metal‐catalyzed hydroamination of unsaturated hydrocarbons is an appealing synthetic tool for the construction high value‐added chiral amines. Despite significant progress in asymmetric alkenes, allenes, and 1,3‐dienes, 1,6‐enynes or 1,7‐enynes remains rather limited due to enormous challenges controlling chemoselectivity stereoselectivity reaction. Herein, we report a Ni‐catalyzed chemo‐ enantioselective reductive cyclization/amidation amination using dioxazolones anthranils as nitrene‐transfer reagents. This mild, modular, practical protocol provides rapid access variety enantioenriched 2‐pyrrolidone 2‐piperidone derivatives bearing aminomethylene group at 4‐position good yields (up 83 %) with excellent enantioselectivities (46 examples, up 99 % ee). Mechanistic experiments density functional theory calculations indicate that reaction initiated by hydronickelation alkynes followed migratory insertion into than [2+2+1] oxidative addition process nickel alkenes alkynes.

Language: Английский

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Cobalt-Catalyzed Stereoselective Synthesis of Chiral Gem-Difluorocyclopropanes with Vicinal Stereocenters

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(23), P. 6617 - 6626

Published: Jan. 1, 2024

We present a cobalt-catalyzed regio-, diastereo-, and enantioselective hydroalkylation of gem -difluorocyclopropenes, accessing chiral -difluorocyclopropanes with vicinal stereocenters.

Language: Английский

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