General Regio- and Diastereoselective Allylic C–H Oxygenation of Internal Alkenes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(27), P. 18218 - 18223

Published: June 26, 2024

Branched allylic esters and carboxylates are fundamental motifs prevalent in natural products drug molecules. The direct C-H oxygenation of internal alkenes represents one the most straightforward approaches, bypassing requirement for an leaving group as classical Tsuji-Trost reaction. However, current methods suffer from limited scope─often accompanied by selectivity issues─thus hampering further development. Herein we report a photocatalytic platform general solution to these problems, enabling coupling diverse with carboxylic acids, alcohols, other

Language: Английский

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Cobalt-Catalyzed Carbon–Heteroatom Transfer Enables Regioselective Tricomponent 1,4-Carboamination

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(12), P. 8508 - 8519

Published: Feb. 21, 2024

Tricomponent cobalt(salen)-catalyzed carbofunctionalization of unsaturated substrates by radical-polar crossover has the potential to streamline access broad classes heteroatom-functionalized synthetic targets, yet reaction platform remained elusive, despite well-developed analogous hydrofunctionalizations mediated high-valent alkylcobalt intermediates. We report herein development a cobalt(salen) catalytic system that enables carbofunctionalization. The entails tricomponent decarboxylative 1,4-carboamination dienes and provides direct route aromatic allylic amines obviating preformed allylation reagents protection oxidation-sensitive amines. merges acridine photocatalysis with regioselective 1,4-carbofunctionalization facilitates radical polar phases coupling process, revealing critical roles reactants, as well ligand effects nature formal species on chemo- regioselectivity.

Language: Английский

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Catalytic Asymmetric Cascade Dearomatization of Indoles via a Photoinduced Pd‐Catalyzed 1,2‐Bisfunctionalization of Butadienes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(26)

Published: April 20, 2024

Photoinduced Pd-catalyzed bisfunctionalization of butadienes with a readily available organic halide and nucleophile represents an emerging attractive method to assemble versatile alkenes bearing various functional groups at the allylic position. However, enantiocontrol and/or diastereocontrol in C-C or C-X bond-formation step have not been solved due open-shell process. Herein, we present cascade asymmetric dearomatization reaction indoles via photoexcited 1,2-biscarbonfunctionalization 1,3-butadienes, wherein control on both electrophile part is achieved for first time photoinduced butadienes. This delivers structurally novel chiral spiroindolenines two contiguous stereogenic centers high diastereomeric ratios (up >20 : 1 dr) good excellent enantiomeric 97 3 er). Experimental computational studies mechanism confirmed radical pathway involving excited-state palladium catalysis. The alignment non-covalent interactions between substrate catalyst were found be essential stereocontrol.

Language: Английский

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Recent advances in C(sp³)–N bond formation via metallaphoto-redox catalysis

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(50), P. 6340 - 6361

Published: Jan. 1, 2024

In this review, the state-of-the-art advances in radical-involved C(sp 3 )–N bond formation via metallaphotoredox catalysis have been highlighted, which are organized according to different catalytic modes, reaction types, and substrate classes.

Language: Английский

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Photoexcited Palladium-Catalyzed Deracemization of Allenes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(30), P. 21137 - 21146

Published: July 18, 2024

The different enantiomers of specific chiral molecules frequently exhibit disparate biological, physiological, or pharmacological properties. Therefore, the efficient synthesis single is particular importance not only to pharmaceutical sector but also other industrial sectors, such as agrochemical and fine chemical industries. Deracemization, a process during which racemic mixture converted into nonracemic product with 100% atom economy theoretical yield, most straightforward method access enantioenriched challenging task due decrease in entropy microscopic reversibility. Axially allenes bear distinctive structure two orthogonal cumulative π-systems are acknowledged synthetically versatile synthons organic synthesis. selective creation axially high optical purity under mild reaction conditions has always been very popular hot topic remains challenging. Herein, photoexcited palladium-catalyzed deracemization nonprefunctionalized disubstituted disclosed. This provides an economical strategy accommodate broad scope good enantioselectivities yields (53 examples, up 96% yield 95% ee). use suitable palladium complex visible light irradiation essential factor achieving this transformation. A metal-to-ligand charge transfer mechanism was proposed based on control experiments density functional theory calculations. Quantum mechanical studies implicate dual modes asymmetric induction behind our new protocol: (1) sterically controlled stereoselective binding one allene enantiomer ground-state (2) facile, noncovalent interaction-driven excited-state isomerization toward opposite enantiomer. success newly established photochemical should provide inspiration for expansion multisubstituted will open mode enantioselective catalysis.

Language: Английский

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Synchronous recognition of amines in oxidative carbonylation toward unsymmetrical ureas

Science, Journal Year: 2024, Volume and Issue: 386(6723), P. 776 - 782

Published: Nov. 14, 2024

Unsymmetrical ureas are commonly found in pharmaceuticals and bioactive compounds. However, devising strategies to introduce two distinct amines selectively the construction of unsymmetrical remains a challenge. In this work, we use synchronous recognition strategy that takes advantage radical nucleophilic activation discriminate between secondary primary amines. Specifically, copper catalyst preferentially oxidizes species, whereas cobalt carbonylates produce amides. Coupling these fragments by cooperative catalysis produces with high selectivity, as showcased modification 41 biologically active compounds six drugs.

Language: Английский

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Selective 1,4-syn-Addition to Cyclic 1,3-Dienes via Hybrid Palladium Catalysis

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(6), P. 1191 - 1200

Published: May 15, 2024

1,4-cis-Disubstituted cyclic compounds play a pivotal role in pharmaceutical development, offering enhanced potency and bioavailability. However, their stereoselective modular synthesis remains long-standing challenge. Here, we report an innovative strategy for accessing these structures via mild conditions employing 1,3-dienes/alkyl(aryl)halides amines. This procedure exhibits wide substrate scope that tolerates various functional groups. The utility of this method is demonstrated the efficient TRPV6 inhibitor, CFTR modulator, other bioactive molecules. Combined experimental computational studies suggest hybrid palladium-catalyzed radical-polar crossover mechanism crucial achieving exceptional 1,4-syn-addition selectivity (dr > 20:1).

Language: Английский

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Photoinduced Electron Donor Acceptor Complex‐Enabled α‐C(sp³)−H Alkenylation of Amines

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(44)

Published: July 13, 2024

Allylic amines are prevalent and vital structural components present in many bioactive compounds natural products. Additionally, they serve as valuable intermediates building blocks, with wide-ranging applications organic synthesis. However, direct α-C(sp

Language: Английский

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Direct Alkylation of Glycine Derivatives via Photoinduced Palladium Catalysis, Utilizing Intermolecular Hydrogen Atom Transfer Mediated by Alkyl Radicals

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(24), P. 15652 - 15662

Published: Nov. 21, 2023

Unveiling the alkyl/Pd hybrid species is a unique sp3-C-centered radical for facilitating intermolecular hydrogen atom transfer (HAT) in development of direct alkylation glycine derivatives. This transformative reaction proceeds smoothly under simple and mild conditions, exhibiting impressive versatility terms substrate scope encompassing both derivatives alkyl bromides while showcasing remarkable tolerance toward diverse functional groups. To shed light on underlying mechanism, extensive investigations involving control experiments, deuterium labeling, clocking, kinetic studies have been conducted. The collected data consistently support pathway formation Pd(I)/alkyl followed by HAT elimination steps that lead to situ imine intermediates, ultimately culminating final stage through addition.

Language: Английский

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Photoinduced Nitrogen-to-Alkyl Radical Relay Heck Reaction of o-Alkylbenzamides with Vinyl Arenes by Palladium Catalysis

Organic Letters, Journal Year: 2023, Volume and Issue: 25(20), P. 3664 - 3669

Published: May 12, 2023

Here, a palladium-catalyzed photoinduced N-to-alkyl radical relay Heck reaction of o-alkylbenzamides at benzylic sites with vinyl arenes is described. The employs neither exogeneous photosensitizers nor external oxidants. It proposed to proceed via hybrid palladium-radical mechanism which occurs under mild conditions that are compatible wide range functional groups. products easily transformed azepinone derivatives, prevalent in pharmaceuticals and natural products.

Language: Английский

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