A Guide to Directing Group Removal: 8‐Aminoquinoline

Chemistry - A European Journal, Год журнала: 2021, Номер 27(33), С. 8411 - 8436

Опубликована: Фев. 10, 2021

The use of directing groups allows high levels selectivity to be achieved in transition metal-catalyzed transformations. Efficient removal these auxiliaries after successful functionalization, however, can very challenging. This review provides a critical overview strategies used for Daugulis' 8-aminoquinoline (2005-2020), one the most widely N,N-bidentate groups. limitations are discussed and alternative approaches suggested challenging substrates. Our aim is provide comprehensive end-users' guide chemists academia industry who want harness synthetic power groups-and able remove them from their final products.

Язык: Английский

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Challenges and Breakthroughs in Selective Amide Activation

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(49)

Опубликована: Сен. 20, 2022

In contrast to ketones and carboxylic esters, amides are classically seen as comparatively unreactive members of the carbonyl family, owing their unique structural electronic features. However, recent decades have emergence research programmes focused on selective activation under mild conditions. past four years, this area has continued rapidly develop, with new advances coming in at a fast pace. Several novel strategies been demonstrated effective tools for amide activation, enabling transformations that once synthetically useful mechanistically intriguing. This Minireview comprises field, highlighting trends breakthroughs what could be called age activation.

Язык: Английский

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Highly Chemoselective Transamidation of Unactivated Tertiary Amides by Electrophilic N−C(O) Activation by Amide‐to‐Acyl Iodide Re‐routing

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(24)

Опубликована: Март 31, 2022

The challenging transamidation of unactivated tertiary amides has been accomplished via cooperative acid/iodide catalysis. Most crucially, the method provides a novel manifold to re-route reactivity N,N-dialkyl through reactive acyl iodide intermediates, thus reverting classical order carboxylic acid derivatives. This direct route amide-to-amide bond interconversion with excellent chemoselectivity using equivalent amounts amines. combination and identified as essential factor activate amide C-N electrophilic catalytic activation, enabling production new desired transamidated products wide substrate scope both amines, including late-stage functionalization complex APIs (>80 examples). We anticipate that this powerful activation mode bonds will find broad-ranging applications in chemical synthesis.

Язык: Английский

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Ni‐Catalyzed Divergent Synthesis of 2‐Benzazepine Derivatives via Tunable Cyclization and 1,4‐Acyl Transfer Triggered by Amide N‐C Bond Cleavage

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(25)

Опубликована: Апрель 6, 2022

Abstract Ligand‐directed divergent synthesis can transform common starting materials into distinct molecular scaffolds by simple tuning different ligands. This strategy enables the rapid construction of structurally rich collection small molecules for biological evaluation and reveals novel modes catalytic transformation, representing one most sought‐after challenges in synthetic chemistry. We herein report a Ni‐catalyzed ligand‐controlled tunable cyclization/cross‐couplings pharmacologically important 2‐benzazepine frameworks. The bidentate ligand facilitates nucleophilic addition aryl halides to amide carbonyl, followed 1,4‐acyl transfer cross‐coupling obtain 2‐benzazepin‐5‐ones benzo[c]pyrano[2,3‐e]azepines. tridentate promotes selective 7‐ endo cyclization/cross‐coupling access 2‐benzazepin‐3‐ones. protocol operates under mild reaction conditions with cyclization patterns that be easily modulated through backbone.

Язык: Английский

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Classes of Amides that Undergo Selective N–C Amide Bond Activation: The Emergence of Ground-State Destabilization

The Journal of Organic Chemistry, Год журнала: 2022, Номер 88(19), С. 13371 - 13391

Опубликована: Сен. 2, 2022

Ground-state destabilization of the N–C(O) linkage represents a powerful tool to functionalize historically inert amide bond. This burgeoning reaction manifold relies on availability bond precursors that participate in weakening nN → π*C=O conjugation through N–C twisting, N pyramidalization, and electronic delocalization. Since 2015, acyl activation ground-state has been achieved by transition-metal-catalyzed oxidative addition bond, generation radicals, transition-metal-free addition. Perspective summarizes contributions our laboratory development new ground-state-destabilized enabled twist synthetic utility amides cross-coupling reactions reactions. The use as electrophiles enables plethora previously unknown transformations such coupling, decarbonylative radical coupling forge C–C, C–N, C–O, C–S, C–P, C–B bonds. Structural studies activated catalytic systems developed past decade enable view change from "traditionally inert" "readily modifiable" functional group with continuum reactivity dictated destabilization.

Язык: Английский

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New Strategies for the Functionalization of Carbonyl Derivatives via α-Umpolung: From Enolates to Enolonium Ions

Accounts of Chemical Research, Год журнала: 2023, Номер 56(12), С. 1634 - 1644

Опубликована: Май 25, 2023

ConspectusUmpolung, a term describing the reversal of innate polarity, has become an indispensable tool to unlock new chemical space by overcoming limitations natural polarity. Introduced Dieter Seebach in 1979, this principle had tremendous impact on synthetic organic chemistry, offering previously inaccessible retrosynthetic disconnections. In contrast great progress made over past decades for generation effective acyl anion synthons, umpolung at α-position carbonyls (converting enolates into enolonium ions) long proved challenging and only recently regained traction. Aiming develop approaches α-functionalization capable complementing enolate our group initiated, nearly 6 years ago, program devoted α-umpolung carbonyl derivatives. Account, following overview established methods, we will summarize findings rapidly developing field. We focus two distinct, yet related, topics classes: (1) amides, where is enabled electrophilic activation, (2) ketones, using hypervalent iodine reagents. Our developed several protocols allow amide subsequent α-functionalization, relying activation. Over course investigations, transformations that are particularly enolate-based approaches, such as direct α-oxygenation, α-fluorination, α-amination amides well synthesis 1,4-dicarbonyls from substrates, have been unlocked. Based some most recent studies, method shown be so general almost any nucleophile can added amide. special emphasis placed discussion mechanistic aspects. It important note area involved shift focus, moving even further away carbonyl, development shall also detailed final subsection highlights latest investigations umpolung-based remote functionalization β- γ-positions amides. The second section Account covers more work dedicated exploration chemistry unlocked through use By placing context previous pioneering achievements, which mainly focused carbonyls, discuss skeletal reorganizations ions unique properties incipient positive charges α electron-deficient moieties. Transformations intramolecular cyclopropanations aryl migrations covered supplemented insight unusual nature intermediate species, including nonclassical carbocations.

Язык: Английский

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Catalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloids

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Окт. 6, 2023

The primary objective in synthetic organic chemistry is to develop highly efficient, selective, and versatile methodologies, which are essential for discovering new drug candidates agrochemicals. In this study, we present a unified strategy one-pot, catalytic enantioselective synthesis of α-alkyl α,α'-dialkyl pyrrolidine, piperidine, indolizidine alkaloids using readily available amides alkynes. This enabled by the identification development an Ir/Cu/N-PINAP catalyzed chemoselective reductive alkynylation α-unbranched aliphatic amides, serves as key reaction. reaction combined with Pd-catalyzed tandem reactions one-pot approach, enabling collective, total syntheses eight anticancer antipode 90-98% ee. methodology's enantio-divergence exemplified one-step access either enantiomer alkaloid bgugaine.

Язык: Английский

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Making Full Use of TMSCF₃: Deoxygenative Trifluoromethylation/Silylation of Amides

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(28), С. 19286 - 19294

Опубликована: Июль 3, 2024

As one of the most powerful trifluoromethylation reagents, (trifluoromethyl)trimethylsilane (TMSCF3) has been widely used for synthesis fluorine-containing molecules. However, to best our knowledge, simultaneous incorporation both TMS- and CF3- groups this reagent onto same carbon products not realized. Herein, we report an unprecedented SmI2/Sm promoted deoxygenative difunctionalization amides with TMSCF3, in which silyl trifluoromethyl are incorporated into final product, yielding α-silyl-α-trifluoromethyl amines high efficiency. Notably, group could be further transformed other functional groups, providing a new method α-quaternary α-CF3-amines.

Язык: Английский

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Halogen Atom Transfer-Induced Homolysis of C–F Bonds by the Excited-State Boryl Radical

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(33), С. 22874 - 22880

Опубликована: Авг. 2, 2024

A novel reactivity toward C-F bond functionalization has been developed, which could be designated as fluorine atom transfer (FAT). photoexcited state of an

Язык: Английский

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Merging SOMO activation with transition metal catalysis: Deoxygenative functionalization of amides to β-aryl amines

Science Advances, Год журнала: 2025, Номер 11(3)

Опубликована: Янв. 17, 2025

Singly occupied molecular orbital (SOMO) activation of in situ generated enamines has achieved great success (asymmetric) α-functionalization carbonyl compounds. However, examples on the use this mode transformations other functional groups are rare, and combination SOMO with transition metal catalysis is still less explored. In area deoxygenative functionalization amides, intermediates such as iminium ions were often to result formation α-functionalized amines. contrast, direct deoxygenation amides β-functionalized amines highly appealing yet remains scarcely investigated. Here, a arylation aryl halides was developed via multicatalysis iridium/photoredox/nickel/iridium, affording β-aryl high efficiency. The key reaction enamine synergy Ni-catalyzed arylation, which conjunction two compatible Ir-catalyzed reduction processes.

Язык: Английский

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