Late-Stage C–H Functionalization of Azines

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(12), P. 7655 - 7691

Published: May 3, 2023

Azines, such as pyridines, quinolines, pyrimidines, and pyridazines, are widespread components of pharmaceuticals. Their occurrence derives from a suite physiochemical properties that match key criteria in drug design is tunable by varying their substituents. Developments synthetic chemistry, therefore, directly impact these efforts, methods can install various groups azine C–H bonds particularly valuable. Furthermore, there growing interest late-stage functionalization (LSF) reactions focus on advanced candidate compounds often complex structures with multiple heterocycles, functional groups, reactive sites. Because factors electron-deficient nature the effects Lewis basic N atom, distinct arene counterparts, application LSF contexts difficult. However, have been many significant advances reactions, this review will describe progress, much which has occurred over past decade. It possible to categorize radical addition processes, metal-catalyzed activation transformations occurring via dearomatized intermediates. Substantial variation reaction within each category indicates both rich reactivity heterocycles creativity approaches involved.

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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Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(3), P. 1030 - 1076

Published: Nov. 18, 2023

Synthetic chemistry plays an indispensable role in drug discovery, contributing to hit compounds identification, lead optimization, candidate drugs preparation, and so on. As Nobel Prize laureate James Black emphasized, "the most fruitful basis for the discovery of a new is start with old drug"

Language: Английский

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Blue Light Irradiated Metal-, Oxidant-, and Base-Free Cross-Dehydrogenative Coupling of C(sp²)–H and N–H Bonds: Amination of Naphthoquinones with Amines

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(11), P. 7401 - 7424

Published: May 12, 2023

Herein, we report a blue-light-driven amination of C(sp2)-H bond naphthoquinones and quinones with the N-H primary secondary amines for synthesis 2-amino-naphthoquinones 2-amino-quinones. The coupling wide array aliphatic, aromatic, chiral, primary, having electron donating (-CH3, -OCH3, -SCH3), withdrawing (-F, -Cl, -Br, -I), CO2H, -OH, -NH2 groups acidic protons selectively occurred to afford C-N coupled in 60-99% yields hydrogen gas as byproduct methanol solvent without using any additional reagents, additives, oxidant under blue light irradiation. Mechanistic insight by DFT computation, controlled experiments, kinetic isotopic effect, substitution effect substrates suggest that reaction proceeds radical pathway which naphthoquinone forms highly oxidizing naphthoquinonyl biradical upon irradiation (457 nm). Consequently, transfer from electron-rich amine an leads anion aminyl cation, followed proton delocalization leading carbon-centered radical. cross-coupling nitrogen radicals bond, subsequent elimination (which was also confirmed GC-TCD), affording 2-amino-1,4-naphthoquinone metal-, reagent-, base-, oxidant-free conditions.

Language: Английский

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Mechanistic Approach Toward the C4‐Selective Amination of Pyridines via Nucleophilic Substitution of Hydrogen

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(24)

Published: April 9, 2024

Abstract The development of site‐selective functionalization N‐heteroarenes is highly desirable in streamlined synthesis. In this context, direct amination pyridines stands as an important synthetic methodology, with particular emphasis on accessing 4‐aminopyridines, a versatile pharmacophore medicinal chemistry. Herein, we report reaction manifold for the C4‐selective by employing nucleophilic substitution hydrogen (S N H). Through 4‐pyridyl pyridinium salt intermediates, 4‐aminopyridine products are obtained aqueous ammonia without intermediate isolation. notable regioselectivity was achieved electronic tuning external pyridine reagents along maximization polarizability proton elimination stage. Further mechanistic investigations provided guiding principle selective C−H pyridination additional N‐heteroarenes, presenting strategic avenue installation diverse functional groups.

Language: Английский

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Combining (CH₂O)_n and (NH₄)₂CO₃ as a Formamidine Equivalent for “Four-in-One” Synthesis of Fluoroalkylated 2-H-Pyrimidines

Organic Letters, Journal Year: 2024, Volume and Issue: 26(33), P. 7078 - 7082

Published: Aug. 9, 2024

Multicomponent reactions hold the potential to maximize synthetic efficiency in preparation of diverse and complex molecular scaffolds. An unprecedented formal [3+1+1+1] annulation approach for one-step synthesis fluoroalkylated 2-H-pyrimidines commencing from perfluoroalkyl alkenes, paraformaldehyde, ammonium carbonate is described. By harnessing readily accessible (CH2O)n cheap (NH4)2CO3 as a formamidine surrogate, this method effectively replaces traditionally preformed amidines with pyrimidine assembly. The multicomponent reaction proceeds step-economical, operationally simple, metal-free, additive-free manner, featuring broad substrate scope, excellent functional group compatibility, scalability. elaboration obtained 2-H-pyrimidine further demonstrated alkylation vinylation its C2 position.

Language: Английский

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Uncanonical Semireduction of Quinolines and Isoquinolines via Regioselective HAT-Promoted Hydrosilylation

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 145(1), P. 25 - 31

Published: Dec. 22, 2022

Heterocycles are the backbone of modern medical chemistry and drug development. The derivatization "an olefin" inside aromatic rings represents an ideal approach to access functionalized saturated heterocycles from abundant building blocks. Here, we report operationally simple, efficient, practical method selectively hydrosilylated reduced N-heterocycles bicyclic aromatics via a key diradical intermediate. This is expected facilitate complex heterocycle functionalizations that enable novel medicinally relevant scaffolds.

Language: Английский

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Photoinduced Transition-Metal-Free Chan–Evans–Lam-Type Coupling: Dual Photoexcitation Mode with Halide Anion Effect

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(20), P. 9161 - 9171

Published: May 12, 2022

Herein, we report a photoinduced transition-metal-free C(aryl)-N bond formation between 2,4,6-tri(aryl)boroxines or arylboronic acids as an aryl source and 1,4,2-dioxazol-5-ones (dioxazolones) amide coupling partner. Chloride anion, either generated

Language: Английский

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Recent Applications of Trifluoromethanesulfonic Anhydride in Organic Synthesis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(10)

Published: Dec. 21, 2022

Abstract Trifluoromethanesulfonic anhydride has been widely used in synthetic organic chemistry, not only for the conversion of various oxygen‐containing compounds to triflates, but also electrophilic activation and further amides, sulfoxides, phosphorus oxides. In recent years, utilization Tf 2 O as an activator nitrogen‐containing heterocycles, nitriles nitro groups become a promising tool development new valuable methods with considerable success. addition, efficient radical trifluoromethylation trifluoromethylthiolation reagent due contained SO CF 3 fragment, significant progress made this area. This review summarizes applications above two aspects, aims illustrate role potential application synthesis.

Language: Английский

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