Hydroamination, Aminoboration, and Carboamination with Electrophilic Amination Reagents: Umpolung-Enabled Regio- and Stereoselective Synthesis of N-Containing Molecules from Alkenes and Alkynes

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(2), С. 648 - 661

Опубликована: Янв. 6, 2022

Nitrogen (N) is ubiquitously found in bioactive molecules, pharmaceutical agents, and organic functional materials. Accordingly, development of new C–N bond-forming catalysis has been one the long-standing research subjects synthetic chemistry. In this Perspective, recent advances highly selective amination reactions with electrophilic reagents are described: by taking advantage concept nitrogen umpolung, otherwise challenging aminofunctionalizations, such as hydroamination, aminoboration, carboamination, readily available feedstock-like alkenes alkynes possible, giving densely functionalized complex often chiral alkylamines high selectivity. The scope, limitations, reaction mechanism briefly summarized.

Язык: Английский

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Enantioselective Synthesis of Isoindolinone by Palladium-Catalyzed Aminoalkynylation of O-Phenyl Hydroxamic Ethers with Alkynes

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(7), С. 4320 - 4326

Опубликована: Фев. 9, 2024

A highly efficient palladium-catalyzed asymmetric tandem aza-Heck/Sonogashira coupling reaction of O-phenyl hydroxamic ethers with terminal alkynes is described. This protocol enables versatile access to challenging chiral isoindolinone derivatives bearing a quaternary stereogenic center. The aminoalkynylation shows broad functional group tolerance and allows the straightforward preparation isoindolinones high efficiency excellent enantioselectivity under mild conditions. DFT calculations were performed disclose mechanism origins enantioselectivity.

Язык: Английский

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Pd-Catalyzed Asymmetric Aza-Heck Cyclization/Sonogashira Reaction of Alkene-Tethered Oxime Esters and Alkynes

ACS Catalysis, Год журнала: 2024, Номер 14(7), С. 5305 - 5313

Опубликована: Март 26, 2024

Over the past few decades, Narasaka–Heck-type difunctionalization of tethered alkenes has emerged as a powerful strategy to produce heterocyclic scaffolds. However, asymmetric synthesis rarely been explored. Herein, we report robust palladium-catalyzed enantioselective Narasaka–Heck cyclization–Sonogashira reaction alkene-tethered oxime esters and terminal alkynes. By employing new Ming-Phos ligand, obtain high yields pyrrolines with quaternary stereocenter enantioselectivities under mild conditions. Density functional theory (DFT) study reveals weak interaction between aromatic ring substrate fragment naphthyl group in which probably accounts for stereoselectivity.

Язык: Английский

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Enantioselective (3+2) Annulation of Donor‐Acceptor Cyclopropanes with Aldehydes and Ketones Catalyzed by Brønsted Bases

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Июль 15, 2024

Abstract The substituted tetrahydrofuran core is a structural motif in many biologically active and natural compounds. However, the scarcity of enantioselective methods developed towards its synthesis makes this field challenging attractive to explore. Herein, first Brønsted‐base catalyzed (3+2) annulation donor‐acceptor cyclopropanes with aldehydes ketones affording enantioenriched 2,3,5‐substituted tetrahydrofurans reported. reaction concept based on activation racemic β‐cyclopropyl by chiral bifunctional Brønsted base which catalyzes for range ketones. For aldehydes, furnished excellent yield, good diastereoselectivity enantioselectivity up >99 % ee . Surprisingly, aromatic afforded cis ‐2,5‐substituted as major diastereoisomer, while aliphatic trans ‐cycloadduct was favored. also proceeds well spiro yields enantioselectivities (up 99 ). Hammett studies have been conducted elucidate influence electronic nature benzaldehydes stereoselectivity. Based diastereochemical outcome two paths are proposed. Finally, diastereoselective synthetic transformations demonstrate potential obtained products.

Язык: Английский

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Directed C–H Functionalization of C3-Aldehyde, Ketone, and Acid/Ester-Substituted Free (NH) Indoles with Iodoarenes via a Palladium Catalyst System

The Journal of Organic Chemistry, Год журнала: 2022, Номер 88(3), С. 1299 - 1318

Опубликована: Май 24, 2022

Pd(II)-catalyzed C-H arylations of free (NH) indoles including different carbonyl directing groups on C3-position with aryl iodides are demonstrated. Importantly, the reactions carried out using same catalyst system without any additional transient group (TDG). In this study, formyl as a gave C4-arylated versus C2-arylation. Using system, functionalization 3-acetylindoles provided domino C4-arylation/3,2-carbonyl migration products. This transformation involves unusual acetyl to C2-position following C4-arylation in one pot. Meanwhile, could be simply controlled and N-protected afforded products group. Functionalization indole-3-carboxylic acid (or methyl ester) present Pd(II)-catalyst resulted decarboxylation followed by formation C2-arylated indoles. Based control experiments literature, plausible mechanisms proposed. The synthetic utilities these acetylindole derivatives have also been Remarkably, acetylindoles allowed construction functionalized pityiacitrin (a natural product).

Язык: Английский

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Cyclopropane-Fused N-Heterocycles via Aza-Heck-Triggered C(sp³)–H Functionalization Cascades

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(37), С. 16749 - 16754

Опубликована: Сен. 9, 2022

Unique examples of aza-Heck-based C(sp3)–H functionalization cascades are described. Under Pd(0)-catalyzed conditions, the aza-Heck-type cyclization N-(pentafluorobenzoyloxy)carbamates generates alkyl–Pd(II) intermediates that effect palladation en route to cyclopropanes. Key factors control site selectivity cyclopropanation process have been elucidated such selective access a wide range ring- or spiro-fused systems can be achieved.

Язык: Английский

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An SN2 Reaction at Amide Nitrogen Enables Hydrazide Synthesis

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(14)

Опубликована: Фев. 17, 2024

Nucleophilic substitutions are fundamentally important transformations in synthetic organic chemistry. Despite the substantial advances bimolecular nucleophilic (S

Язык: Английский

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Construction of NH‐Unprotected Spiropyrrolidines and Spiroisoindolines by [4+1] Cyclizations of γ‐Azidoboronic Acids with Cyclic N‐Sulfonylhydrazones

Angewandte Chemie International Edition, Год журнала: 2021, Номер 61(2)

Опубликована: Окт. 22, 2021

The reactions of N-sulfonylhydrazones derived from cyclic ketones with γ-azidopropylboronic acid and 2-(azidomethyl)phenylboronic give rise to spirocyclic pyrrolidines spiroisoindolines, respectively. proceed without the need any transition-metal catalyst through a domino process that comprises formation Csp3 -C -N bond former hydrazonic carbon. scope reaction has been explored by preparation over 50 examples NH-unprotected derivatives. Importantly, this methodology could be applied for alkaloid steroids steroid N-tosylhydrazones.

Язык: Английский

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A Computational mechanistic study on the Pd(II)-catalyzed γ-C(sp³)-H lactamization and Further Rational Design

Catalysis Science & Technology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

DFT calculations were conducted to study the catalytic mechanism of Pd( ii )-catalyzed γ-C(sp3)–H lactamization reaction and rationally design new promising ligands.

Язык: Английский

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N-Tosyl-1,2,3-triazoles as Scaffolds for Morpholines: The Total Synthesis of (–)-Chelonin A

Synlett, Год журнала: 2022, Номер 34(12), С. 1524 - 1528

Опубликована: Ноя. 18, 2022

Abstract Substituted morpholine derivatives appear frequently in biologically active compounds and thus novel routes towards such structures are of great synthetic interest. Herein, we report the total syntheses chelonin A, a morpholine-derived marine natural product with reported antibacterial anti-inflammatory activity. The key step this process was rhodium carbenoid 1,3-insertion into bromohydrin O–H bond, followed by annulation, leading to 2,6-disubstituted-3,4-dihydro-2H-1,4-oxazine core. This work then extended deliver first asymmetric synthesis (–)-chelonin A using an enantioenriched bromohydrin, prepared turn via transfer hydrogenation α-bromoketone.

Язык: Английский

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