Dearomatization of Pyridines: Photochemical Skeletal Enlargement for the Synthesis of 1,2-Diazepines

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(4), P. 2845 - 2854

Published: Jan. 18, 2024

In this report, we developed a unified and standardized one-pot sequence that converts pyridine derivatives into 1,2-diazepines by inserting nitrogen atom. This skeletal transformation capitalizes on the in situ generation of 1-aminopyridinium ylides, which rearrange under UV light irradiation. A thorough evaluation key parameters (wavelength, reaction conditions, activating agent) allowed us to elaborate simple, mild, user-friendly protocol. The model was extrapolated more than 40 examples, including drug derivatives, affording unique 7-membered structures. Mechanistic evidence supports transient presence diazanorcaradiene species. Finally, pertinent transformations products, ring contraction reactions form pyrazoles, were conducted paved way broad application

Language: Английский

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Synthesis of ¹⁵N-Pyridines and Higher Mass Isotopologs via Zincke Imine Intermediates

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 2944 - 2949

Published: Jan. 16, 2024

Methods to incorporate stable radioisotopes are integral pharmaceutical and agrochemical development. However, despite the prevalence of pyridines in candidate compounds, methods 15N atoms within their structures limited. Here, we present a general approach pyridine 15N-labeling that proceeds via ring-opening NTf-Zincke imines then ring-closure with commercially available 15NH4Cl salts. This process functions on range substituted pyridines, from simple building block-type compounds late-stage labeling complex pharmaceuticals, 15N-incorporation is >95% most cases. The reactivity Zincke imine intermediates also enables deuteration C3- C5-positions, resulting higher mass isotopologs required for LCMS analysis biological fluids during drug

Language: Английский

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A deconstruction-reconstruction strategy for pyrimidine diversification

Nature, Journal Year: 2024, Volume and Issue: 631(8019), P. 87 - 93

Published: May 2, 2024

Language: Английский

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The green chemistry paradigm in modern organic synthesis

Russian Chemical Reviews, Journal Year: 2023, Volume and Issue: 92(12), P. RCR5104 - RCR5104

Published: Dec. 1, 2023

After the appearance of green chemistry concept, which was introduced in vocabulary early 1990s, its main statements have been continuously developed and modified. Currently, there are 10–12 cornerstones that should form basis for an ideal chemical process. This review analyzes accumulated experience achievements towards design products processes reduce or eliminate use generation hazardous substances. The presents views leading Russian scientists specializing various fields this subject, including homogeneous heterogeneous catalysis, fine basic organic synthesis, electrochemistry, polymer chemistry, based on bio-renewable feedstocks energetic compounds materials. A new approach to quantitative evaluation environmental friendliness by authors is described. <br> bibliography includes 1761.

Language: Английский

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Enantioselective C3‐Allylation of Pyridines via Tandem Borane and Palladium Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(34)

Published: July 3, 2023

Abstract Herein, we report a one‐pot method for enantioselective C−H allylation of pyridines at C3 via tandem borane and palladium catalysis. This involves borane‐catalyzed pyridine hydroboration to generate dihydropyridines, then palladium‐catalyzed the dihydropyridines with allylic esters, finally air oxidation allylated afford products. enables introduction an group excellent regio‐ enantioselectivities.

Language: Английский

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Photoinduced Cobalt Catalysis for the Reductive Coupling of Pyridines and Dienes Enabled by Paired Single‐Electron Transfer**

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(45)

Published: Sept. 7, 2023

Abstract Selective hydroarylation of dienes has potential to provide swift access useful building blocks. However, most existing methods rely on stabilised by an aromatic group and transmetallation or nucleophilic attack steps require electron‐rich aryl coupling partners. As such, there are few examples which tolerate wide‐spread heteroarenes such as pyridine. Whilst allylic C−H functionalisation could be considered alternative approach, the positional selectivity unsymmetrical substrates is hard control. Here, we report a general approach for selective hydropyridylation under mild conditions using metal catalysed hydrogen‐atom transfer. Photoinduced, reductive enable simultaneous formation cobalt‐hydride catalyst persistent radical easily‐synthesised pyridyl phosphonium salts. This facilitates in traceless manner at C4‐position wide‐range pyridine substrates. The mildness method underscored its functional‐group tolerance demonstrated applications late‐stage functionalisation. Based combination experimental computational studies, propose mechanistic pathway proceeds through non‐reversible transfer (HAT) from cobalt hydride species uniquely presence other olefins due much higher relative barrier associated with olefin HAT.

Language: Английский

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Reductive Functionalization of Pyridine-Fused N-Heteroarenes

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(5), P. 795 - 813

Published: Feb. 23, 2024

ConspectusThe selective functionalization/transformation of ubiquitous pyridine-fused N-heteroarenes is a practical method to synthesize structurally novel N-heterocycles, which important for the development medicines, bioactive agents, agrochemicals, materials, ligands, sensors, pigments, dyes, etc. However, owing thermodynamic stability, kinetic inertness, and lone electron pair–induced catalyst deactivation N-heteroarenes, limited strategies (e.g., C–H activation/functionalization, electrophilic substitution, Minisci reaction) are available realize synthetic purpose maintain aromaticity final products. Moreover, relevant transformations have limitations such as needing harsh reaction conditions, requiring preinstallation specific coupling agents containing transformable functionalities or directing groups, using less environmentally benign oxidants and/or acidic activators, poor selectivity. Herein, considering that imines, enamines, radicals, cyclic amines generated during reduction precise transformation these reductive intermediates offers fundamental basis developing tandem reactions. Our group revealed slow rate, synergistic catalysis, controlled electroreduction effective fulfilling functionalization N-heteroarenes. Thus, we established series new methods provide diverse construction modalities functionalized N-heterocycles. The striking features include high efficiency, atom economy, use readily accessible feedstocks in absence flammable pressurized H2 gas, alongside promising potential obtained N-heterocyclic present study would be appealing fields organic chemistry, biomedical functional materials. This Account describes application dearomatization substrate-activating reaction-initiating modes summarizes via alkylation, arylation, annulation at nitrogen, α, β, other remote carbon sites achieved over past 8 years. Details regarding reactions their plausible mechanisms perspectives discussed. We hope our contributions this field will aid further tackle intractable challenges area.

Language: Английский

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Photochemical Skeletal Editing of Pyridines to Bicyclic Pyrazolines and Pyrazoles

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(31), P. 21389 - 21400

Published: June 14, 2024

We present an efficient one-pot photochemical skeletal editing protocol for the transformation of pyridines into diverse bicyclic pyrazolines and pyrazoles under mild conditions. The method requires no metals, photocatalysts, or additives allows selective removal specific carbon atoms from pyridines, allowing unprecedented versatility. Our approach offers a convenient means late-stage modification complex drug molecules by replacing core pyridine skeleton. Moreover, we have successfully scaled up this procedure in stop-flow flow-chemistry systems, showcasing its applicability to intricate transformations such as Diels–Alder reaction, hydrogenation, [3 + 2] cycloaddition, Heck reaction. Through control experiments DFT calculations, provide insights mechanistic underpinnings protocol.

Language: Английский

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Phototriggered Self-Catalyzed Phosphorylation of 3,4-Dihydroquinoxalin-2(1H)-ones with Diarylphosphine Oxides in EtOH

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

A highly effective external photocatalyst- and additive-free method for the phosphorylation of 3,4-dihydroquinoxalin-2(1

Language: Английский

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Introduction of the difluoromethyl group at the meta- or para-position of pyridines through regioselectivity switch

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 15, 2024

Abstract Difluoromethyl pyridines have gained significant attention in medicinal and agricultural chemistry. The direct C−H-difluoromethylation of represents a highly efficient economic way to access these azines. However, the meta-difluoromethylation has remained elusive methods for site-switchable regioselective meta- para-difluoromethylation are unknown. Here, we demonstrate meta-C−H-difluoromethylation through radical process by using oxazino pyridine intermediates, which easily accessed from pyridines. selectivity can be readily switched para situ transformation pyridinium salts upon acid treatment. preparation various para-difluoromethylated this approach is presented. mild conditions used also allow late-stage or containing drugs. Sequential double functionalization presented, further underlines value work.

Language: Английский

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