Energy-Transfer-Enabled Dearomative Cycloaddition Reactions of Indoles/Pyrroles via Excited-State Aromatics

Accounts of Chemical Research, Год журнала: 2022, Номер 55(17), С. 2510 - 2525

Опубликована: Авг. 9, 2022

Exploring the enormous chemical space through an expedient building-up of molecular diversity is important goal organic chemistry. The development synthetic methods toward molecules with unprecedented structural motifs lays foundation for wide applications ranging from pharmaceutical chemistry to materials science. In this regard, dearomatization arenes has been recognized as a unique strategy since it provides novel retrosynthetic disconnections various spiro or fused polycyclic increased saturation and stereoisomerism. However, inherent thermodynamic challenges are associated processes. disruption aromaticity arene substrates usually requires large energy inputs, which makes harsh conditions necessary many ground-state reactions. Therefore, further expansion scope reactions remains major problem not fully solved in chemistry.The past decade witnessed tremendous progress on photocatalytic under visible light. Particularly, via transfer mechanism have unlocked new opportunities Mediated by appropriately chosen photosensitizers, aromatic can be excited. This kind precise input might make feasible some that otherwise unfavorable thermal because significant increases substrates. Nevertheless, lifetimes key intermediates energy-transfer-enabled reactions, such excited-state aromatics downstream biradical species, quite short. How regulate reactivities these transient achieve exclusive selectivity certain reaction pathway among possibilities crucial issue addressed.Since 2019, our group reported series visible-light-induced dearomative cycloaddition indole pyrrole derivatives. It was found units excited irradiation light presence suitable photosensitizer. These readily undergo [m + n] tethered unsaturated functionalities including alkenes, alkynes, N-alkoxy oximes, (hetero)arenes, vinylcyclopropanes. yield indolines pyrrolines highly strained small- and/or medium-sized rings embedded, possess bridge- cagelike topologies. Systematic mechanistic studies confirmed involvement process. Density functional theory (DFT) calculations revealed correlation between substrate structure excitation efficiency, accelerated optimization parameters. Meanwhile, DFT demonstrated competition kinetically thermodynamically controlled pathways open-shell singlet intermediates, allowed complete switches [2 2] 1,5-hydrogen atom oximes [4 naphthalene. Furthermore, ab initio dynamics (AIMD) simulations uncovered post-spin crossing dynamic effects, determine regioselectivity recombination step pyrrole-derived vinylcyclopropanes.An increasing number scientists joined research contributed more elegant examples area. mechanism, although still its infancy, exhibited great potential synthesis hardly accessed other methods. We believe future will push boundary find related disciplines.

Язык: Английский

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Cascade asymmetric dearomative cyclization reactions via transition-metal-catalysis

Nature Synthesis, Год журнала: 2022, Номер 1(3), С. 203 - 216

Опубликована: Март 14, 2022

Язык: Английский

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Silver‐Catalyzed Dearomative [2π+2σ] Cycloadditions of Indoles with Bicyclobutanes: Access to Indoline Fused Bicyclo[2.1.1]hexanes**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(48)

Опубликована: Окт. 12, 2023

Bicyclo[2.1.1]hexanes (BCHs) are becoming ever more important in drug design and development as bridged scaffolds that provide underexplored chemical space, but difficult to access. Here a silver-catalyzed dearomative [2π+2σ] cycloaddition strategy for the synthesis of indoline fused BCHs from N-unprotected indoles bicyclobutane precursors is described. The strain-release operates under mild conditions, tolerating wide range functional groups. It capable forming with up four contiguous quaternary carbon centers, achieving yields 99 %. In addition, scale-up experiment synthetic transformations cycloadducts further highlighted utility.

Язык: Английский

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Photoredox-Enabled Dearomative [2π + 2σ] Cycloaddition of Phenols

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(4), С. 2789 - 2797

Опубликована: Янв. 18, 2024

Dearomative photocycloaddition of monocyclic arenes is an appealing strategy for comprehending the concept "escape from flatland". This brings replacement readily available planar aromatic hydrocarbon units with a 3D fused bicyclic core sp3-enriched carbon units. Herein, we outline intermolecular approach dearomative phenols. In order to circumvent ground-state aromaticity and construct conformationally restrained building blocks, bicyclo[1.1.0]butanes were chosen as coupling partners. renders straightforward access bicyclo[2.1.1]hexane unit cyclic enone moiety, which further contributed synthetic linchpin postmodifications. Mechanistic experiment advocates plausible onset both reactants, depending on redox potential.

Язык: Английский

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Synthesis of Chiral Spirolactams via Sequential C−H Olefination/Asymmetric [4+1] Spirocyclization under a Simple Co^II/Chiral Spiro Phosphoric Acid Binary System

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(43), С. 23187 - 23192

Опубликована: Авг. 26, 2021

Abstract An unprecedented enantioselective synthesis of spiro‐γ‐lactams via a sequential C−H olefination/asymmetric [4+1] spirocyclization under simple Co II /chiral spiro phosphoric acid (SPA) binary system is reported. A range biologically important are obtained with high levels enantioselectivity (up to 98 % ee ). The concise, asymmetric an aldose reductase inhibitor was successfully achieved. Notably, contrast previous reports that relied on the use cyclopentadienyl or its derivatives (achiral Cp*, Cp tBu , chiral x ) ligated III complexes requiring tedious steps prepare, cheap and commercially available cobalt(II) acetate tetrahydrate used as efficient precatalyst.

Язык: Английский

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Brønsted Acid Catalyzed Dearomatization by Intramolecular Hydroalkoxylation/Claisen Rearrangement: Diastereo‐ and Enantioselective Synthesis of Spirolactams

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(52), С. 27164 - 27170

Опубликована: Окт. 21, 2021

Described herein is a novel Brønsted acid catalyzed intramolecular hydroalkoxylation/Claisen rearrangement, allowing the practical and atom-economic synthesis of range valuable spirolactams from readily available ynamides in generally good to excellent yields with diastereoselectivities broad substrate scope. Importantly, an unexpected dearomatization nonactivated arenes heteroaromatic compounds involved this tandem sequence. Moreover, asymmetric version cyclization was also achieved by efficient kinetic resolution chiral phosphoric catalysis. In addition, [3,3]-rearrangement shown be kinetically preferred over related [1,3]-rearrangement theoretical calculations.

Язык: 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, Год журнала: 2021, Номер 143(48), С. 20462 - 20471

Опубликована: Ноя. 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.

Язык: Английский

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Facile access to fused 2D/3D rings via intermolecular cascade dearomative [2 + 2] cycloaddition/rearrangement reactions of quinolines with alkenes

Nature Catalysis, Год журнала: 2022, Номер 5(5), С. 405 - 413

Опубликована: Май 25, 2022

Abstract Hybrid fused two-dimensional/three-dimensional (2D/3D) rings are important pharmacophores in drugs owing to their unique structural and physicochemical properties. Preparation of these strained ring systems often requires elaborate synthetic effort exhibits low efficiency, thus representing a limiting factor drug discovery. Here, we report two types energy-transfer-mediated cascade dearomative [2 + 2] cycloaddition/rearrangement reactions quinoline derivatives with alkenes, which provide straightforward avenue 2D/3D pyridine-fused 6−5−4−3- 6−4−6-membered systems. Notably, this strategy features excellent diastereoselectivity that bypasses the general reactivity selectivity issues photochemical cycloaddition various other aromatics. Tuning aza-arene substitutions enabled selective diversion iridium photocatalysed energy transfer manifold towards either cyclopropanation or cyclobutane-rearrangement products. Density functional theory calculations revealed scenario be operative.

Язык: Английский

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Enantioselective Access to Spirolactams via Nitrenoid Transfer Enabled by Enhanced Noncovalent Interactions

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(17), С. 6363 - 6369

Опубликована: Апрель 22, 2021

Described herein is the Ir-catalyzed enantioselective access to chiral spirolactam products via nitrenoid transfer aromatic ipso-carbons. The key strategy for precise stereocontrol enhance secondary attractive and repulsive interactions between catalyst substrates by introduction of a traceless O-silyl achiral auxiliary, thus effectively differentiating two prochiral faces arenol-derived 1,4,2-dioxazol-5-one substrates.

Язык: Английский

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Organocatalytic Asymmetric Dearomatizing Hetero-Diels–Alder Reaction of Nonactivated Arenes

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(16), С. 7374 - 7381

Опубликована: Апрель 13, 2022

Nonactivated arenes, such as benzene derivatives, are chemically inert due to their intrinsic aromaticity and low polarity. The catalytic asymmetric dearomatization (CADA, coined by You co-workers) of the nonactivated arenes represents a formidable challenge. We herein demonstrated an organocatalytic dearomatizing hetero-Diels–Alder reaction derivatives. tunable regioselectivity this strategy allowed delivery diversity stereochemically complex polycyclic compounds oxahelicenes with excellent stereoselectivity. high complexity three-dimensionality products crucial for potential applications in materials science drug discovery. Mechanistic studies suggested that proceeds through chiral tetra-substituted vinylidene ortho-quinone methide (VQM) intermediate, which is extremely active overcome loss derivatives concomitant chirality transfer.

Язык: Английский

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