Enantioselective [3+2] Annulation of Aldimines with Alkynes by Scandium‐Catalyzed C−H Activation

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

Published: Jan. 3, 2025

Abstract The enantioselective [3+2] annulation of readily accessible aldimines with alkynes via C−H activation is, in principle, a straightforward and atom‐efficient route for synthesizing chiral 1‐aminoindenes, which are important components wide array natural products, bioactive molecules, functional materials. However, such asymmetric transformation has remained undeveloped to date due the lack suitable catalysts. Here, we report first time using half‐sandwich scandium This protocol enabled synthesis diverse multi‐substituted 1‐aminoindene derivatives 100 % atom‐efficiency, broad substrate scope, high regio‐ enantioselectivity. Density theory (DFT) analyses have revealed that noncovalent C−H⋅⋅⋅π interaction between tert ‐Bu substituent cyclopentadienyl (Cp) ligand phenyl ring an aromatic aldimine played role achieving level work not only offers efficient selective new family but also unprecedented insights into enantioselectivity control Cp‐ligated metal

Language: Английский

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Divergent Synthesis of Multi‐Substituted Aminotetralins via [4+2] Annulation of Aldimines with Alkenes by Rare‐Earth‐Catalyzed Benzylic C(sp³)−H Activation

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(13)

Published: Jan. 16, 2024

The search for efficient and selective methods the divergent synthesis of multi-substituted aminotetralins is much interest importance. We report herein first time diastereoselective [4+2] annulation 2-methyl aromatic aldimines with alkenes via benzylic C(sp

Language: Английский

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Regio- and Diastereoselective Annulation of α,β-Unsaturated Aldimines with Alkenes via Allylic C(sp³)–H Activation by Rare-Earth Catalysts

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(14), P. 10187 - 10198

Published: March 28, 2024

The [3 + 2] or [4 annulation of α,β-unsaturated aldimines with alkenes via β′- γ-allylic C(sp3)–H activation is, in principle, an atom-efficient route for the synthesis five- six-membered-ring cycloalkylamines, which are important structural motifs numerous natural products, bioactive molecules, and pharmaceuticals. However, such a transformation has remained undeveloped to date probably due lack suitable catalysts. We report herein first time regio- diastereoselective annulations imines allylic by half-sandwich rare-earth catalysts having different metal ion sizes. reaction α-methyl-substituted C5Me4SiMe3-ligated scandium catalyst took place trans-diastereoselective fashion at α-methyl group (β′-position), exclusively affording alkylidene-functionalized cyclopentylamines excellent trans-diastereoselectivity. In contrast, β-methyl-substituted C5Me5-ligated cerium proceeded cis-diastereoselective activation, selectively yielding multisubstituted 2-cyclohexenylamines cis-diastereoselectivity. mechanistic details these transformations have been elucidated deuterium-labeling experiments, kinetic isotope effect studies, isolation key intermediates. This work offers efficient selective protocol new family cycloalkylamine derivatives, featuring 100% atom efficiency, high diastereoselectivity, broad substrate scope, unprecedented mechanism.

Language: Английский

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Theoretical Insights into Rare-Earth-Catalyst-Controlled Diastereo- and Enantioselective [3 + 2] Annulation of Aromatic Aldimines with Styrenes

Inorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Rare-earth-catalyzed annulation reactions using alkenes via C–H activation offer an atom-efficient approach to constructing cyclic compounds. However, the mechanisms underlying these remain poorly understood, limiting rational design of related catalytic systems. Recently, Hou and Cong reported unprecedented example rare-earth-catalyst-controlled diastereodivergent asymmetric [3 + 2] aromatic aldimines with alkenes. To elucidate origins diastereo- enantioselectivity, density functional theory calculations were performed. The results revealed that styrene insertion step determines stereoselectivity. Styrene follows a similar metal–styrene interaction pattern across different catalysts. Specifically, during cis-insertion, interacts strongly metal center, exhibiting significant Sc···Ph interactions, whereas such interactions are absent trans-insertion. Thus, when catalyst is employed small ligand, stereoselectivity primarily governed by electronic factors, favoring cis-insertion mode. In contrast, for more sterically hindered catalyst, in insufficient overcome steric effects, leading preference trans-insertion mode, which minimizes hindrance. These findings deeper insights into catalyst-controlled enantioselectivity will also contribute stereospecific rare-earth catalysis.

Language: Английский

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(Z)-Selective Isomerization of 1,1-Disubstituted Alkenes by Scandium-Catalyzed Allylic C–H Activation

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(39), P. 26766 - 26776

Published: Sept. 20, 2024

The isomerization of 1,1-disubstituted alkenes through 1,3-hydrogen shift is an atom-efficient route for synthesizing trisubstituted alkenes, which are important moieties in many natural products, pharmaceuticals, and organic materials. However, this reaction often encounters regio- stereoselectivity challenges, typically yielding

Language: Английский

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Regio- and Stereoselective Hydroalkynylation of Internal Alkynes with Terminal Alkynes by Half-Sandwich Rare-Earth Catalysts

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

Published: Feb. 5, 2025

The regio- and stereoselective hydroalkynylation of internal alkynes with terminal is great interest importance as a straightforward route for synthesizing multisubstituted 1,3-enynes. However, this transformation often suffers from stereoselectivity issues when working unsymmetrical alkynes. Herein, we report the first time syn-stereoselective variety heteroatom-functionalized including homopropargyl ethers, thioethers, tertiary amines by half-sandwich rare-earth catalysts. This protocol provides an atom-efficient synthesis new family heteroatom (O, S, or N)-functionalized 1,3-enynes, featuring 100% atom-efficiency, broad substrate scope, high syn-stereoselectivity (>19:1 r.r. >19:1 syn/anti). mechanistic details have been elucidated deuterium-labeling experiments, control isolation transformations key reaction intermediates, revealing that proceeded through C(sp)–H deprotonation alkyne scandium alkyl species to form catalytically active dimeric tetraalkynyl followed heteroatom-assisted insertion into Sc–alkynyl bond subsequent protonolysis resulting Sc–alkenyl another molecule. coordination N) catalyst metal center plays critically important role in achieving level reactivity stereoselectivity. Remarkably, can be recovered reused, constituting example recyclable system

Language: Английский

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The Effect of Basic Ligands and Alkenes on the Regioselectivity of C−H Additions of Tertiary Amines to Alkenes

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(32)

Published: April 4, 2024

Abstract Highly regioselective C−H alkylation reactions of tertiary anilines and alkyl amines with simple alkenes have been achieved by the use imidazolin‐2‐iminato scandium complexes. This protocol provided an efficient atom‐economical route to structurally diverse amine derivatives. The basic ligand, a coordinating THF in catalyst substitution alkene substrates were found switch regioselectivity presumably due generation different types catalytically active species or formation relatively stable intermediates. On basis deuterium labeling experiments KIE experiments, possible catalytical cycles understand reaction mechanism as well regioselectivity.

Language: Английский

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Enantioselective [3+2] Annulation of Aldimines with Alkynes by Scandium‐Catalyzed C−H Activation

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

Published: Jan. 3, 2025

Abstract The enantioselective [3+2] annulation of readily accessible aldimines with alkynes via C−H activation is, in principle, a straightforward and atom‐efficient route for synthesizing chiral 1‐aminoindenes, which are important components wide array natural products, bioactive molecules, functional materials. However, such asymmetric transformation has remained undeveloped to date due the lack suitable catalysts. Here, we report first time using half‐sandwich scandium This protocol enabled synthesis diverse multi‐substituted 1‐aminoindene derivatives 100 % atom‐efficiency, broad substrate scope, high regio‐ enantioselectivity. Density theory (DFT) analyses have revealed that noncovalent C−H⋅⋅⋅π interaction between tert ‐Bu substituent cyclopentadienyl (Cp) ligand phenyl ring an aromatic aldimine played role achieving level work not only offers efficient selective new family but also unprecedented insights into enantioselectivity control Cp‐ligated metal

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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Enantioselective ortho-C–H Addition of Aromatic Amines to Alkenes by Bulky Chiral Anilido-Oxazoline Scandium Complexes

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

Published: April 8, 2025

The enantioselective C-H addition of anilines to alkenes represents an ideal protocol for the synthesis chiral aromatic amines in terms step- and atom-economy. However, this field remains predominantly unexplored. Herein, a series newly designed bulky anilido-oxazoline ligand precursors were synthesized, corresponding rare-earth metal alkyl complexes obtained successfully. resultant scandium exhibit high regioselectivity ortho-C-H tertiary unactivated alkenes, providing wide range alkylated yields (up 98% yield) with excellent enantioselectivity ee). Moreover, products can be easily converted into biorelevant derivatives pharmacophore-containing skeletons.

Language: Английский

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