Asymmetric Three-Component Radical Alkene Carboazidation by Direct Activation of Aliphatic C–H Bonds

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(19), С. 13347 - 13355

Опубликована: Май 6, 2024

Azide compounds are widely present in natural products and drug molecules, their easy-to-transform characteristics make them used the field of organic synthesis. The merging transition-metal catalysis with radical chemistry offers a versatile platform for carboazidation alkenes, allowing rapid assembly highly functionalized azides. However, direct use readily available hydrocarbon feedstocks as sp

Язык: Английский

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The Carbene Chemistry of N-Sulfonyl Hydrazones: The Past, Present, and Future

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

N-Sulfonyl hydrazones have been extensively used as operationally safe carbene precursors in modern organic synthesis due to their ready availability, facile functionalization, and environmental benignity. Over the past two decades, there has tremendous progress chemistry of N-sulfonyl presence transition metal catalysts, under metal-free conditions, or using photocatalysts photoirradiation conditions. Many transfer reactions are unique cannot be achieved by any alternative methods. The discovery novel development highly enantioselective new skeletal editing represent notable recent achievements hydrazones. This review describes overall made hydrazones, organized based on reaction types, spotlighting current state-of-the-art remaining challenges addressed future. Special emphasis is devoted identifying, describing, comparing scope limitations methodologies, key mechanistic scenarios, potential applications complex molecules.

Язык: Английский

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Asymmetric Radical Cyclopropanation of α,β-Unsaturated Amides with α-Boryl and α-Silyl Dibromomethanes via Cr(II)-Based Metalloradical Catalysis

Journal of the American Chemical Society, Год журнала: 2025, Номер 147(9), С. 7282 - 7292

Опубликована: Фев. 20, 2025

Transition-metal-catalyzed asymmetric carbene-transfer reactions represent a powerful strategy for synthesizing chiral cyclopropanes. However, current methods predominantly rely on stabilized carbene-bearing α-π-conjugated groups, restricting access to less carbenes, such as α-silyl and α-boryl carbenes. Herein, we present an unprecedented Cr(II)-based metalloradical system the cyclopropanation of α,β-unsaturated amides with dibromomethanes in presence Mn reducing agent. Employing chromium complex, reaction proceeds under mild conditions, yielding cyclopropanes three contiguous stereocenters high diastereo- enantioselectivities. This method features Cr-catalyzed radical-based stepwise mechanism. The broad substrate scope, encompassing various amides, demonstrates protocol's versatility robustness. Mechanistic insights, supported by experimental computational studies, suggest formation α-Cr(III)-alkyl radical intermediates, delineating pathway distinct from that classical concerted cyclopropanations. approach provides tool highly functionalized cyclopropanes, offering potential applications drug discovery development.

Язык: Английский

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Stereoselective Synthesis of Silyl Enol Ethers with Acylsilanes and α,β-Unsaturated Ketones

Organic Letters, Год журнала: 2024, Номер 26(28), С. 5911 - 5916

Опубликована: Июль 8, 2024

Acylsilanes are emerging bench-stable reagents for the generation of electron-rich oxycarbenes that difficult to access with unstable diazo compounds. Herein, we report a siloxycarbene-mediated stereoselective synthesis silyl enol ethers through visible-light-induced intermolecular reactions between acylsilanes and α,β-unsaturated ketones. Both solvent low temperature important success reaction. This approach features atomic economics, exclusive stereocontrol, broad substrate scope. The synthetic potential this methodology is demonstrated by gram-scale reaction various downstream transformations including requiring configuration purity ethers.

Язык: Английский

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Nature-Inspired Radical Pyridoxal-Mediated C–C Bond Formation

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(33), С. 23321 - 23329

Опубликована: Авг. 6, 2024

Pyridoxal-5'-phosphate (PLP) and derivatives of this cofactor enable a plethora reactions in both enzyme-mediated free-in-solution transformations. With few exceptions each category, such chemistry has predominantly involved two-electron processes. This sometimes poses significant challenge for using PLP to build tetrasubstituted carbon centers, especially when the reaction is reversible. The ability access radical pathways paramount broadening scope catalyzed by coenzyme. In study, we demonstrate PLP-based intermediate engage number C-C bond-forming reactions. By selection an appropriate oxidant, single-electron oxidation quinonoid can be achieved, which subsequently applied Through pathway, synthesized series α-tertiary amino acids esters investigate substrate identify nonproductive pathways. Beyond acid model system, that other classes amine substrates range small molecule reagents serve as coupling partners semiquinone radical. We anticipate versatile species will central development novel

Язык: Английский

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Design and Synthesis of C₄‐Symmetric Axially Chiral β‐Aryl Porphyrins and Application for Supporting Ir(III)‐Catalyzed Enantioselective C−H Alkylation

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(28)

Опубликована: Апрель 29, 2024

A hitherto unknown class of C

Язык: Английский

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Highly diastereoselective and enantioselective cyclopropanation of alkenes catalyzed by a chiral iridium(III) porphyrin complex

Chem Catalysis, Год журнала: 2025, Номер unknown, С. 101262 - 101262

Опубликована: Фев. 1, 2025

Язык: Английский

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Designing Ruthenium Phthalocyanine with Chiral Pockets Formed by (1R,2S,5R)-Menthoxy Groups for Enantioselective Catalysis

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 4984 - 5001

Опубликована: Март 10, 2025

Unprecedented chiral ruthenium(II) complexes with phthalocyanines having motifs near the catalytic metal site have been prepared by cross condensation of 3,6-bis-aryloxy-phthalonitrile (α-Ar*O)2Pn bearing two (1R,2S,5R)-menthoxy groups orthogonal to aromatic plane and (15-crown-5)phthalonitrile. Four containing menthyl (M) 15-crown-5 units (C), notably RuPc[MC3](CO), RuPc[opp-M2C2](CO), RuPc[adj-M2C2](CO), RuPc[M3C](CO), were isolated in pure form fully characterized UV–vis, circular dichroism, HRMS, various 1H NMR 13C techniques. Their evaluation benchmark asymmetric cyclopropanation reaction styrene derivatives ethyl diazoacetate indicated that RuPc[opp-M2C2](CO) complex was most efficient terms diastereo- enantioselectivity. Further study revealed strong dependence stereoselectivity on solvent nature salt additives, which caused conformational rearrangement flexible surrounding, as evidenced multinuclear CD spectra. For instance, upon moving from commonly used CH2Cl2 EtOH addition NaPF6, a significant enhancement enantioselectivity (from 35 84% p-methylstyrene) obtained. Of particular importance is very high diastereoselectivity many substrates promoted incorporation sodium cations into crown ether cavities phthalocyanine attain trans/cis ratio up 499:1. Such regulating effect catalysis involving tetrapyrrolic has not previously observed, rendering this prominent example tunable catalyst. The developed synthetic strategy paves way environment around receptors tune properties.

Язык: Английский

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Asymmetric amination of alkyl radicals with two minimally different alkyl substituents

Science, Год журнала: 2025, Номер 388(6744), С. 283 - 291

Опубликована: Апрель 17, 2025

Differentiating between similar alkyl groups is a major challenge in asymmetric catalysis. Achieving enantiocontrol over unactivated prochiral radicals even more difficult owing to their high reactivity and limited interactions with chiral catalysts. In this study, we report copper-catalyzed amination of secondary radicals, using specifically designed anionic multidentate ligands radical substitution reaction. This approach efficiently produces highly enantioenriched α-chiral amines facilitates the enantioselective formal synthesis series important drug molecules. Mechanistic studies reveal that bulky peripheral modifications on help create truncated cone-shaped pocket, enabling precise enantiodiscrimination through steric hindrance noncovalent interactions. strategy holds broad potential for transformations involving diverse nucleophiles.

Язык: Английский

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Manganese-Catalyzed Cycloalkene Ring Expansion Synthesis of Azaheterocycles

Опубликована: Июнь 18, 2024

Radical chemistry is synthetically useful but can be plagued by the non-intuitive reaction course and indiscriminate reactivity profile. Herein, dynamic radical effect revealed as a conceptual logic for predictive achievement of selectivity. The reversible bonding association/dissociation two radicals serves synthetic handle directing one to target recourse, without participation other radical. A Mn catalytic protocol has been developed cycloalkene ring expansion synthesis azaheterocycles. An initial azidyl addition alkene subsequent O2 occupation C-radical site prevents further coupling steers toward intramolecular rearrangement pathway. broad substrate scope established pyridine isoquinoline derivatives. This new perspective promises an important guiding principle empowering radical-based chemical transformations.

Язык: Английский

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