Radical Pathway Glycosylation Empowered by Bench-Stable Glycosyl Donors

Accounts of Chemical Research, Год журнала: 2023, Номер 56(18), С. 2473 - 2488

Опубликована: Авг. 18, 2023

ConspectusThe study of carbohydrates has emerged as a crucial research area in various disciplines due to their pivotal roles cellular processes. To facilitate in-depth exploration biological functions, chemical glycosylation reactions that allow facile access glycoconjugates broad community are highly needed. In classical reactions, glycosyl donor is activated by an acid generate reactive electrophilic intermediate, which subsequently forms glycosidic bond upon reaction with nucleophilic acceptor. Such ionic pathway been the mainstay technique for glycoconjugate synthesis and allowed numerous intricate structures. Nevertheless, limitations still exist. For instance, when labile donors or harsh activating conditions required, these methods show limited tolerance hydroxyl groups abundant on sugar rings. addition, achieving good stereocontrol represents another longstanding obstacle. recent years, new modes activation have sought tackle above challenges.We noted passing through intermediacy radicals via cascade single-electron transfer steps possess significant but underexplored potential. Progress this slow large part dearth handy maneuver radicals. Most existing call either forcing unstable/inconvenient starting materials. order better exploit power radical glycosylation, we developed range donors─namely, sulfoxides, sulfones, sulfinates─that bench stable can be readily prepared from simple These form under mild conditions. Enabled use donors, series could used making O-, S-, C-glycosides, some were previously difficult access. many cases, no protecting group required. As illustration potential utility, our adopted preparation sugar–drug conjugates, sugar–DNA glycopeptides, even glycoproteins. While most cases intrinsic reactivity intermediates explored axially configured products, also utilization external, delicate reagents, catalysts override such innate preference achieve catalyst-controlled stereoselectivity.We believe enormous inspire development novel glycoside synthesis. Account, highlight design principles summarize advancements enabled use, provide outlook future directions field.

Язык: Английский

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Electrophilic Halospirocyclization of N-Benzylacrylamides to Access 4-Halomethyl-2-azaspiro[4.5]decanes

The Journal of Organic Chemistry, Год журнала: 2023, Номер 88(19), С. 13610 - 13621

Опубликована: Сен. 11, 2023

An electrophilic spirocyclization of N-benzylacrylamides with N-halosuccinimides (NXS) as the halogenating reagents has been developed. This reaction is carried out at room temperature under simple conditions without relying on metal reagents, photochemistry, or electrochemistry, providing a fast and efficient route to synthesize wide variety 4-halomethyl-2-azaspiro[4.5]decanes satisfactory yields. The approach further highlighted through gram-scale synthesis diverse transformations spiro products.

Язык: Английский

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Reductive Deoxygenative Functionalization of Alcohols by First‐Row Transition Metal Catalysis

Chinese Journal of Chemistry, Год журнала: 2023, Номер 41(13), С. 1637 - 1652

Опубликована: Янв. 23, 2023

Comprehensive Summary Alcohols are among the most accessible functionalities. Catalytic deoxygenative functionalization of alcohols is highly synthetically appealing. While significant progress has been made on reactions with nucleophiles, electrophilic coupling partners remain a real challenge. This manuscript highlights advance in this direction, which mainly achieved by first‐row transition metals. The low‐valent titanium catalyst shown unique reactivity to homolytically cleave C—OH bonds. formed carbon radicals could either undergo reduction give protonation products or couple fragments form C—C chemistry initially realized using stoichiometric amount reagents and later extended catalytic variants. Nickel features variety oxidation states ranging from Ni 0 IV , both two‐electron oxidative addition single‐electron process involved their activation an electrophile. These properties enable nickel catalyze reductive R–X electrophiles. reaction first reported allylic alcohols, then benzylic and, very recently non‐activated alcohols. Recent effort resulted many invaluable methodologies that improve efficiency for construction aliphatic use cobalt copper catalysts not only expands substrate scope these but also shows new selectivity issues.

Язык: Английский

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Enantioselective Reductive Cross-Couplings of Olefins by Merging Electrochemistry with Nickel Catalysis

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(44), С. 23910 - 23917

Опубликована: Окт. 26, 2023

The merger of electrochemistry and transition metal catalysis has emerged as a powerful tool to join two electrophiles in an enantioselective manner. However, the development electroreductive cross-couplings olefins remains challenge. Inspired by advantages synergistic use with nickel catalysis, we present here Ni-catalyzed cross-coupling acrylates aryl halides alkyl bromides, which affords chiral α-aryl carbonyls good excellent enantioselectivity. Additionally, this catalytic reaction can be applied (hetero)aryl chlorides, is difficult achieve other methods. combination cyclic voltammetry analysis electrode potential studies suggests that NiI species activates oxidative addition bromides single-electron transfer.

Язык: Английский

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Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions

Chemical Reviews, Год журнала: 2024, Номер 124(9), С. 6078 - 6144

Опубликована: Апрель 17, 2024

Alcohols are abundant and attractive feedstock molecules for organic synthesis. Many methods their functionalization require them to first be converted into a more activated derivative, while recent years have seen vast increase in the number of complexity-building transformations that directly harness unprotected alcohols. This Review discusses how transition metal catalysis can used toward this goal. These broadly classified three categories. Deoxygenative functionalizations, representing derivatization C–O bond, enable alcohol act as leaving group formation new C–C bonds. Etherifications, characterized by O–H represent classical reactivity has been modernized include mild reaction conditions, diverse partners, high selectivities. Lastly, chain reactions described, wherein acts mediator formal C–H alkyl backbone. Each these classes transformation will discussed context intermolecular arylation, alkylation, related reactions, illustrating alcohols harnessed

Язык: Английский

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Electroreduction of unactivated alkenes using water as hydrogen source

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 30, 2024

Abstract Herein, we report an electroreduction of unactivated alkyl alkenes enabled by [Fe]-H, which is provided through the combination anodic iron salts and silane generated in situ via cathodic reduction, using H 2 O as H-source. The catalytic amounts Si-additive work H-carrier from to generate a highly active species under continuous electrochemical conditions. This approach shows broad substrate scope good functional group compatibility. In addition hydrogenation, use D instead provides desired deuterated products yields with excellent D-incorporation (up >99%). Further late-stage hydrogenation complex molecules drug derivatives demonstrate potential application pharmaceutical industry. Mechanistic studies are performed provide support for proposed mechanistic pathway.

Язык: Английский

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Insights into Recent Nickel-Catalyzed Reductive and Redox C–C Coupling of Electrophiles, C(sp³)–H Bonds and Alkenes

Accounts of Chemical Research, Год журнала: 2024, Номер 57(8), С. 1149 - 1162

Опубликована: Март 28, 2024

ConspectusTransition metal-catalyzed reductive cross-coupling of two carbon electrophiles, also known as cross-electrophile coupling (XEC), has transformed the landscape C–C chemistry. Nickel catalysts, in particular, have demonstrated exceptional performance facilitating XEC reactions, allowing for diverse elegant transformations by employing various electrophiles to forge bonds. Nevertheless, several crucial challenges remain be addressed. First, intrinsic chemoselectivity between structurally similar Ni-catalyzed C(sp3)–C(sp3) and C(sp2)–C(sp2) not been well understood; this necessitates an excess one partners achieve synthetically useful outcomes. Second, substitution economically environmentally benign nonmetal reductants Zn/Mn can help scale up reactions avoid trace metals pharmaceutical products, but research direction progressed slowly. Finally, it is highly warranted leverage mechanistic insights from develop innovative thermoredox protocols, specifically designed tackle associated with difficult substrates such C(sp3)–H bonds unactivated alkenes.In Account, we address aforementioned issues reviewing our recent work on C–X C–O strategy alkenes, use diboron esters coupling. We focus perspectives transformations, particularly how key C–NiIII–C intermediates are generated, order explain chemoselective regioselective results. The Account consists four sections. discuss Zn/Mn-mediated bond formations based selected alkyl/aryl, allyl/benzyl, other electrophiles. describe versatile C(sp3)–C(sp2) couplings, emphasis consideration construction Third, leveraging C(sp3)–O effective C(sp3)–C formation via situ halogenation alcohols preparation α-vinylated -arylated unusual amino esters. In final section, illustrate functionalization challenging aryl alkyl halides afford taking advantage compatibility Zn oxidant di-tert-butylperoxide (DTBP). Furthermore, a SiH/DTBP-mediated hydrodimerization terminal alkenes selectively head-to-head methyl branched This process, conducted presence or absence catalytic CuBr2, provides solution long-standing challenge: site-selective hydrocoupling produce

Язык: Английский

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Asymmetric Cross-Coupling of Aldehydes with Diverse Carbonyl or Iminyl Compounds by Photoredox-Mediated Cobalt Catalysis

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(15), С. 10857 - 10867

Опубликована: Апрель 8, 2024

The asymmetric cross-coupling of unsaturated bonds, hampered by their comparable polarity and reactivity, as well the scarcity efficient catalytic systems capable diastereo- enantiocontrol, presents a significant hurdle in organic synthesis. In this study, we introduce highly adaptable photochemical cobalt catalysis framework that facilitates chemo- stereoselective reductive cross-couplings between common aldehydes with broad array carbonyl iminyl compounds, including N-acylhydrazones, aryl ketones, aldehydes, α-keto esters. Our methodology hinges on synergistic mechanism driven photoredox-induced single-electron reduction subsequent radical–radical coupling, all precisely guided chiral catalyst. Various optically enriched β-amino alcohols unsymmetrical 1,2-diol derivatives (80 examples) have been synthesized good yields (up to 90% yield) high stereoselectivities >20:1 dr, 99% ee). Of particular note, approach accomplishes unattainable transformations disparate partners without reliance any external photosensitizer, thereby further emphasizing its versatility cost-efficiency.

Язык: Английский

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Cobalt-Catalyzed Enantiospecific Dynamic Kinetic Cross-Electrophile Vinylation of Allylic Alcohols with Vinyl Triflates

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(39), С. 15930 - 15935

Опубликована: Сен. 27, 2021

Asymmetric cross-electrophile coupling has emerged as a promising tool for producing chiral molecules; however, the potential of this chemistry with metals other than nickel remains unknown. Herein, we report cobalt-catalyzed enantiospecific vinylation reaction allylic alcohol vinyl triflates. This work establishes new method synthesis enantioenriched 1,4-dienes. The proceeds through dynamic kinetic approach, which not only allows direct functionalization alcohols but also is essential to achieve high chemoselectivity. use cobalt enables reactions proceed enantiospecificity, have failed be realized by catalysts.

Язык: Английский

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Nickel‐Catalyzed, Reductive C(sp³)−Si Cross‐Coupling of α‐Cyano Alkyl Electrophiles and Chlorosilanes

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(34), С. 18587 - 18590

Опубликована: Июль 2, 2021

A nickel/zinc-catalyzed cross-electrophile coupling of alkyl electrophiles activated by an α-cyano group and chlorosilanes is reported. Elemental zinc the stoichiometric reductant in this reductive process. By this, a C(sp

Язык: Английский

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