Metalloradical Catalysis: General Approach for Controlling Reactivity and Selectivity of Homolytic Radical Reactions

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(20)

Опубликована: Март 13, 2024

Abstract Since Friedrich Wöhler's groundbreaking synthesis of urea in 1828, organic over the past two centuries has predominantly relied on exploration and utilization chemical reactions rooted two‐electron heterolytic ionic chemistry. While one‐electron homolytic radical chemistry is both rich fundamental reactivities attractive with practical advantages, synthetic application been long hampered by formidable challenges associated control reactivity selectivity high‐energy intermediates. To fully harness untapped potential for synthesis, there a pressing need to formulate radically different concepts broadly applicable strategies address these outstanding issues. In pursuit this objective, researchers have actively developing metalloradical catalysis (MRC) as comprehensive framework guide design general approaches controlling stereoselectivity reactions. Essentially, MRC exploits metal‐centered radicals present open‐shell metal complexes catalysts activation substrates generate metal‐entangled key intermediates govern reaction pathway stereochemical course subsequent catalytic processes. Different from conventional transition complexes, operates through utilizing stepwise mechanisms.

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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Diastereoselective Transfer of Tri(di)fluoroacetylsilanes‐Derived Carbenes to Alkenes

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

Опубликована: Апрель 13, 2022

Stereoselective cyclopropanation reaction of alkenes is usually achieved by metal complexes via singlet-metal-carbene intermediates. However, previous transition-metal-catalyzed with acylsilanes afforded low diastereoselectivity. Herein, we report the first visible-light-induced transition-metal-free terminal trifluoroacetylsilanes and difluoroacetylsilanes. Both aromatic aliphatic as well electron-deficient are suitable substrates for highly cis-selective [2+1] cyclization reaction. A combination experimental computational studies identified triplet carbenes being key intermediates in this transformation. The gram scale late-stage functionalization demonstrated synthetic potential strategy.

Язык: Английский

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Carbene Radicals in Transition-Metal-Catalyzed Reactions

ACS Catalysis, Год журнала: 2023, Номер 13(8), С. 5428 - 5448

Опубликована: Апрель 6, 2023

Discovered as organometallic curiosities in the 1970s, carbene radicals have become a staple modern-day homogeneous catalysis. Carbene exhibit nucleophilic radical-type reactivity orthogonal to classical electrophilic diamagnetic Fischer carbenes. Their successful catalytic application has led synthesis of myriad carbo- and heterocycles, ranging from simple cyclopropanes more challenging eight-membered rings. The field matured employ densely functionalized chiral porphyrin-based platforms that high enantio-, regio-, stereoselectivity. Thus far focus largely been on cobalt-based systems, but interest growing for past few years expand other transition metals. This Perspective covers advances made since 2011 gives an overview coordination chemistry, reactivity, radical species using metal complexes catalysts.

Язык: Английский

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Biomimetic asymmetric catalysis

Science China Chemistry, Год журнала: 2023, Номер 66(6), С. 1553 - 1633

Опубликована: Апрель 25, 2023

Язык: Английский

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Asymmetric Radical Bicyclization for Stereoselective Construction of Tricyclic Chromanones and Chromanes with Fused Cyclopropanes

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(21), С. 11622 - 11632

Опубликована: Май 2, 2023

Asymmetric radical bicyclization processes have been developed via metalloradical catalysis (MRC) to stereoselectively construct chiral chromanones and chromanes bearing fused cyclopropanes. Through optimization of a versatile

Язык: Английский

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A Photoenzymatic Strategy for Radical‐Mediated Stereoselective Hydroalkylation with Diazo Compounds

Angewandte Chemie International Edition, Год журнала: 2022, Номер 62(5)

Опубликована: Дек. 7, 2022

Carbene insertion reactions initiated with diazo compounds have been widely used to develop unnatural enzymatic reactions. However, alternative functionalization of in processes has unexploited. Herein, we describe a photoenzymatic strategy for radical-mediated stereoselective hydroalkylation compounds. This method generates carbon-centered radicals through an ene reductase catalyzed photoinduced electron transfer process from compounds, enabling the synthesis γ-stereogenic carbonyl good yields and stereoselectivities. study further expands possible reaction patterns photo-biocatalysis offers new approach solving selectivity challenges

Язык: Английский

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Stereoselective gem-Difunctionalization of Diazo Compounds with Vinyl Sulfoxonium Ylides and Thiols via Metalloradical Catalysis

ACS Catalysis, Год журнала: 2024, Номер 14(4), С. 2805 - 2815

Опубликована: Фев. 8, 2024

Multicomponent reactions that involve carbenes with nucleophiles and electrophiles have demonstrated broad applications in synthetic chemistry. However, because of the high reactivity transient carbenes, involving two carbene precursors nucleophile presence a metal catalyst remain unexplored. Herein, three-component stereoselective gem-difunctionalization diazo compounds thiols vinyl sulfoxonium ylide is disclosed via Co(II)-based metalloradical catalysis. The key aspect present strategy to exploit intrinsic difference ylides thiol catalysts. Doyle–Kirmse rearrangement sulfonium involves convergent assembly situ-generated intermediates, such as allyl sulfide α- metalloalkyl radical complex, provide expeditious access tertiary scaffolds. Combined experimental quantum chemical calculations unveil intricate mechanism this reaction. Furthermore, theoretical studies on noncovalent interactions selectivity-determining transition states explain origin experimentally obtained diastereoselectivity.

Язык: Английский

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Catalytic Diastereo‐ and Enantioselective Cyclopropanation of gem‐Dihaloalkanes and Terminal Olefins

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(28)

Опубликована: Май 11, 2023

Chiral cyclopropane derivatives are essential in synthetic chemistry and drug discovery. Their synthesis commonly relies on asymmetric cyclopropanation of diazo compounds, potentially explosive needing stabilizing substituents. Thus, catalytic transformations non-stabilized carbenes or carbenoids remain a formidable challenge. Herein, we report the unprecedented chromium-catalyzed readily available gem-dihaloalkanes terminal olefins. Distinct from previous approaches, serve as suitable precursors for carbenoids, furnishing various functionalized chiral cyclopropanes. Mechanistic studies, including radical trapping, non-linear effect, UV/Vis spectroscopy, provide insights into process, featuring radical-polar crossover.

Язык: Английский

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