Diboron(4)‐Catalyzed Remote [3+2] Cycloaddition of Cyclopropanes via Dearomative/Rearomative Radical Transmission through Pyridine

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(52)

Опубликована: Ноя. 8, 2022

Abstract Ring structures such as pyridine, cyclopentane or their combinations are important motifs in bioactive molecules. In contrast to previous cycloaddition reactions that necessitated a directly bonded initiating functional group, this work demonstrated novel through‐(hetero)arene radical transmission concept for selective activation of remote bond. An efficient, metal‐free and atom‐economical [3+2] between 4‐pyridinyl cyclopropanes alkenes alkynes has been developed modular synthesis pyridine‐substituted cyclopentanes, cyclopentenes bicyclo[2.1.1]hexanes difficult access using known methods. This complexity‐building reaction was catalyzed by very simple inexpensive diboron(4) compound took place via dearomative/rearomative processes. The substrate scope broad more than 100 new compounds were prepared generally high yields. Mechanistic experiments density function theory (DFT) investigation supported relay catalytic cycle involving alkylidene dihydropyridine intermediates boronyl transfer.

Язык: Английский

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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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¹⁴N to ¹⁵N Isotopic Exchange of Nitrogen Heteroaromatics through Skeletal Editing

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(5), С. 2950 - 2958

Опубликована: Янв. 29, 2024

The selective modification of nitrogen heteroaromatics enables the development new chemical tools and accelerates drug discovery. While methods that focus on expanding or contracting skeletal structures are emerging, for direct exchange single core atoms remain limited. Here, we present a method 14N → 15N isotopic several aromatic heterocycles. This isotope transmutation occurs through activation heteroaromatic substrate by triflylation atom, followed ring-opening/ring-closure sequence mediated 15N-aspartate to effect atom. Key success this transformation is formation an isolable 15N-succinyl intermediate, which undergoes elimination give isotopically labeled heterocycle. These transformations occur under mild conditions in high yields.

Язык: Английский

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Alkyl/Glycosyl Sulfoxides as Radical Precursors and Their Use in the Synthesis of Pyridine Derivatives**

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(31)

Опубликована: Июнь 1, 2022

We report here the use of simple and readily available alkyl sulfoxides as precursors to radicals their application in preparation pyridine derivatives. show that sulfoxides, N-methoxy pyridinium salts fluoride anions form electron donor-acceptor (EDA) complexes solution, which, upon visible light irradiation, undergo a radical chain process afford various derivatives smoothly. This reaction displays broad scope with respect both pyridiniums. The synthetic versatility handle chemistry adds power precursors. Glycosyl are converted corresponding pyridyl C-glycosides high stereoselectivities. Computational experimental studies provide insights into mechanism.

Язык: Английский

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Enantioselective functionalization at the C4 position of pyridinium salts through NHC catalysis

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Апрель 1, 2022

Abstract A catalytic method for the enantioselective and C4-selective functionalization of pyridine derivatives is yet to be developed. Herein, we report an efficient asymmetric β-pyridylations enals that involve N-heterocyclic carbene (NHC) catalysis with excellent control over enantioselectivity pyridyl C4-selectivity. The key strategy precise stereocontrol involves enhancing interactions between chiral NHC-bound homoenolate pyridinium salt in presence hexafluorobenzene, which effectively differentiates two faces radical. Room temperature sufficient this transformation, reaction efficiency further accelerated by photo-mediation. This methodology exhibits broad functional group tolerance enables facile access a diverse range enantioenriched β-pyridyl carbonyl compounds under mild metal-free conditions.

Язык: Английский

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Photochemical Organocatalytic Functionalization of Pyridines via Pyridinyl Radicals

Journal of the American Chemical Society, Год журнала: 2022, Номер 145(1), С. 47 - 52

Опубликована: Дек. 27, 2022

We report a photochemical method for the functionalization of pyridines with radicals derived from allylic C–H bonds. Overall, two substrates undergo to form new C(sp2)–C(sp3) bond. The chemistry harnesses unique reactivity pyridinyl radicals, generated upon single-electron reduction pyridinium ions, which effective coupling radicals. This novel mechanism enables distinct positional selectivity pyridine that diverges classical Minisci chemistry. Crucial was identification dithiophosphoric acid masters three catalytic tasks, sequentially acting as Brønsted protonation, single electron transfer (SET) reductant ion reduction, and hydrogen atom abstractor activation C(sp3)–H resulting then couple high regioselectivity.

Язык: Английский

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Generation and Use of Glycosyl Radicals under Acidic Conditions: Glycosyl Sulfinates as Precursors

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(16)

Опубликована: Фев. 10, 2023

We herein report a method that enables the generation of glycosyl radicals under highly acidic conditions. Key to success is design and use sulfinates as radical precursors, which are bench-stable solids can be readily prepared from commercial starting materials. This development allows installation units onto pyridine rings directly by Minisci reaction. further demonstrate utility this in late-stage modification complex drug molecules, including anticancer agent camptothecin. Experimental studies provide insight into reaction mechanism.

Язык: Английский

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C–H functionalization of pyridines

Organic & Biomolecular Chemistry, Год журнала: 2023, Номер 21(28), С. 5671 - 5690

Опубликована: Янв. 1, 2023

This review discusses known approaches for selective pyridine C–H editing, focusing on recent discoveries uniquely suited to pyridines.

Язык: Английский

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C–H Functionalization of Pyridines via Oxazino Pyridine Intermediates: Switching to para-Selectivity under Acidic Conditions

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(28), С. 15581 - 15588

Опубликована: Июль 10, 2023

para-Selective C-H functionalization of pyridines holds a significant value but remains underdeveloped. Site-switchable under easily tunable conditions expedites drug development. We recently reported redox-neutral dearomatization-rearomatization strategy for meta-C-H via oxazino pyridine intermediates. Here, we demonstrate that these intermediates undergo highly para-selective simply by switching to acidic conditions. A broad scope para-alkylated and arylated is prepared through radical as well ionic pathways. These mild catalyst-free methods are applied the late-stage para-functionalization drugs using limiting reagents. Consecutive meta,para-difunctionalization also achieved with complete regiocontrol relying on pH-dependent reactivity pyridines.

Язык: Английский

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Site-selective arene C–H amination with iron-aminyl radical

Nature Catalysis, Год журнала: 2024, Номер 7(6), С. 636 - 645

Опубликована: Апрель 1, 2024

Язык: Английский

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