Site-selective C–H functionalization to access the arene backbone of indoles and quinolines

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(20), P. 11249 - 11269

Published: Jan. 1, 2021

The site-selective C-H bond functionalization of heteroarenes can eventually provide chemists with great techniques for editing and building complex molecular scaffolds. During the past decade, benzo-fused N-heterocycles such as indoles quinolines have been among most widely investigated organic templates. Early developments led to on pyrrole pyridine cores quinolines; however, benzenoid ring has remained a challenge in catalysis. In this review, we elaborate recent highly challenging bonds less-reactive core quinolines. These findings are mainly described selective directing group assisted strategies, remote their reaction mechanisms. underlying principle each strategy is elucidated, which aims facilitate design more advanced structure heterocycles based bioactive molecules, synthetic drugs, material aspects. Moreover, challenges perspectives catalytic access arene backbone also proposed conclusion section.

Language: Английский

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Transition-metal-catalyzed C–H bond alkylation using olefins: recent advances and mechanistic aspects

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(17), P. 7358 - 7426

Published: Jan. 1, 2022

Transition metal catalysis has contributed immensely to C-C bond formation reactions over the last few decades, and alkylation is no exception. The superiority of such methodologies traditional evident from minimal reaction steps, shorter times, atom economy while also allowing control regio- stereo-selectivity. In particular, hydrocarbonation alkenes grabbed increased attention due its fundamental ability effectively selectively synthesise a wide range industrially pharmaceutically relevant moieties. This review attempts provide scientific viewpoint systematic analysis recent developments in transition-metal-catalyzed various C-H bonds using simple activated olefins. key features mechanistic studies involved these transformations are described briefly.

Language: Английский

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Synthesis of Rigid Stepladder Polymers via Scandium-Catalyzed Polyspiroannulation of Quinoline with Alkyne

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

Published: Jan. 1, 2025

Polymers with rigid three-dimensional architectures have attracted significant attention due to their high rigidity and intrinsic microporosity. Here, we report the synthesis of a new class stepladder polymers featuring unique spirodihydroquinoline skeletons. Under catalysis half-sandwich scandium catalyst, quinoline compounds bearing both an aryl substituent (e.g., phenyl or naphthyl) alkynyl group C≡CSiMe3) selectively undergo dearomative polyspiroannulation between skeleton alkyne unit via ortho-C–H activation group. This reaction efficiently yields comprising quaternary carbon stereocenter unprotected N–H Treatment N–H-containing alkyl lithium reagent followed by methyl iodide leads quantitative formation corresponding N-methylated polymers, which exhibit enhanced thermal stability porosity compared counterparts.

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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Enantioselective C–H Alkenylation of Ferrocenes with Alkynes by Half-Sandwich Scandium Catalyst

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(6), P. 2470 - 2476

Published: Feb. 2, 2021

The enantioselective C–H alkenylation of ferrocenes with alkynes is, in principle, a straightforward and atom-efficient route for the construction planar-chiral ferrocene scaffolds bearing alkene functionality but has remained scarcely explored to date. Here we report first time highly quinoline- pyridine-substituted by half-sandwich scandium catalyst. This protocol features broad substrate scope, high enantioselectivity, 100% atom efficiency, selectively affording new family N/alkene functionalities. mechanistic details have been clarified DFT analyses. use quinoline/alkene-functionalized product as chiral ligand asymmetric catalysis is also demonstrated.

Language: Английский

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Modular Access to Spiro-dihydroquinolines via Scandium-Catalyzed Dearomative Annulation of Quinolines with Alkynes

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(48), P. 20462 - 20471

Published: Nov. 23, 2021

The catalytic enantioselective construction of three-dimensional molecular architectures from planar aromatics such as quinolines is great interest and importance the viewpoint both organic synthesis drug discovery, but there still exist many challenges. Here, we report scandium-catalyzed asymmetric dearomative spiro-annulation with alkynes. This protocol offers an efficient selective route for spiro-dihydroquinoline derivatives containing a quaternary carbon stereocenter unprotected N–H group readily accessible diverse alkynes, featuring high yields, enantioselectivity, 100% atom-efficiency, broad substrate scope. Experimental density functional theory studies revealed that reaction proceeded through C–H activation 2-aryl substituent in quinoline by scandium alkyl (or amido) species followed alkyne insertion into Sc–aryl bond subsequent 1,2-addition resulting alkenyl to C═N unit moiety. work opens new avenue dearomatization quinolines, leading spiro were previously difficult access other means.

Language: Английский

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C–H functionalization with alkenes, allenes, and alkynes by half-sandwich rare-earth catalysts

Tetrahedron, Journal Year: 2023, Volume and Issue: 135, P. 133323 - 133323

Published: Feb. 23, 2023

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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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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Mechanisms and Origins of Regioselectivity in Rare-Earth-Catalyzed C–H Functionalization of Anisoles and Thioanisoles

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

Published: March 12, 2025

The direct catalytic C–H functionalization of aromatic compounds such as anisoles and thioanisoles is great interest significance. However, achieving precise regioselectivity remains a major challenge. In this study, we conducted comprehensive density functional theory calculations to explore the mechanisms rare-earth-catalyzed regioselective alkylation, borylation, silylation anisole thioanisole. results reveal that in cationic alkylation systems, alkene insertion step follows substrate-assisted mechanism, which an additional substrate molecule acts ligand facilitate transformation. neutral borylation although mononuclear hydride species readily dimerize into binuclear due thermodynamic stability, process predominantly proceeds via pathway. Furthermore, origins were thoroughly elucidated. A detailed analysis electronic steric effects related transition states reveals that, for anisole, primarily governed by ring strain. Since α-C(sp3)–H activation involves formation highly strained three-membered ring, reaction preferentially occurs at ortho-C(sp2)–H site, forming less four-membered ring. contrast, thioanisole, play decisive role, driving more negatively charged α-C(sp3) site stronger metal–carbon interactions.

Language: Английский

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