Photocatalytic Late-Stage C–H Functionalization

Chemical Reviews, Год журнала: 2023, Номер 123(8), С. 4237 - 4352

Опубликована: Янв. 24, 2023

The emergence of modern photocatalysis, characterized by mildness and selectivity, has significantly spurred innovative late-stage C–H functionalization approaches that make use low energy photons as a controllable source. Compared to traditional strategies, photocatalysis paves the way toward complementary and/or previously unattainable regio- chemoselectivities. Merging compelling benefits with workflow offers potentially unmatched arsenal tackle drug development campaigns beyond. This Review highlights photocatalytic strategies small-molecule drugs, agrochemicals, natural products, classified according targeted bond newly formed one. Emphasis is devoted identifying, describing, comparing main mechanistic scenarios. draws critical comparison between established ionic chemistry photocatalyzed radical-based manifolds. aims establish current state-of-the-art illustrate key unsolved challenges be addressed in future. authors aim introduce general readership functionalization, specialist practitioners evaluation methodologies, potential for improvement, future uncharted directions.

Язык: Английский

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Recent Advances in Pyridinium Salts as Radical Reservoirs in Organic Synthesis

ACS Catalysis, Год журнала: 2019, Номер 9(10), С. 8943 - 8960

Опубликована: Авг. 28, 2019

Pyridinium salts are valuable building blocks, which have been widely applied in various organic transformations during the past few decades. In particular, N-functionalized pyridinium explored as convenient radical precursors, would go through reductive single-electron transfer. As a result, chemistry of such compounds for generating carbon-, nitrogen-, and oxygen-centered radicals has witnessed, remarkable progress achieved, making it hot topic over last five years. This Review describes recent advances area concerning development reactions involving synthesis.

Язык: Английский

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Pyridinium Salts as Redox‐Active Functional Group Transfer Reagents

Angewandte Chemie International Edition, Год журнала: 2019, Номер 59(24), С. 9264 - 9280

Опубликована: Окт. 10, 2019

Abstract In this Review, we highlight recent advances in the understanding and design of N‐functionalized pyridinium scaffolds as redox‐active, single‐electron, functional group transfer reagents. We provide a selection representative methods that demonstrate reactivity fundamental emerging field. The these reagents can be divided into two divergent pathways: homolytic fragmentation to liberate N‐bound substituent corresponding radical or an alternative heterolytic liberates N‐centered radical. A short description elementary steps involved induced by single‐electron is also critically discussed guide readers towards processes thought occur under conditions.

Язык: Английский

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Nitrogen-Centered Radicals in Functionalization of sp² Systems: Generation, Reactivity, and Applications in Synthesis

Chemical Reviews, Год журнала: 2022, Номер 122(9), С. 8181 - 8260

Опубликована: Март 14, 2022

The chemistry of nitrogen-centered radicals (NCRs) has plentiful applications in organic synthesis, and they continue to expand as our understanding these reactive species increases. utility intermediates is demonstrated the recent advances C–H amination (di)amination alkenes. Synthesis previously challenging structures can be achieved by efficient functionalization sp2 moieties without prefunctionalization, allowing for faster more streamlined synthesis. This Review addresses generation, reactivity, application NCRs, including, but not limited to, iminyl, aminyl, amidyl, aminium species. Contributions from early discovery up most examples have been highlighted, covering radical initiation, thermolysis, photolysis, and, recently, photoredox catalysis. Radical-mediated intermolecular (hetero)arenes occur with a variety complex amine precursors, generating aniline derivatives, an important class drug development. Functionalization olefins achievable high anti-Markovnikov regioselectivity allows access difunctionalized when intermediate carbon are trapped. Additionally, reactivity NCRs harnessed rapid construction N-heterocycles such pyrrolidines, phenanthridines, quinoxalines, quinazolinones.

Язык: Английский

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Photocatalytic Generation of Aminium Radical Cations for C–N Bond Formation

ACS Catalysis, Год журнала: 2020, Номер 10(20), С. 11712 - 11738

Опубликована: Сен. 11, 2020

Aminium radical cations have been extensively studied as electrophilic aminating species that readily participate in C–N bond forming processes with alkenes and arenes. However, their utility synthesis has limited, generation required unstable, reactive starting materials harsh reaction conditions. Visible-light photoredox catalysis emerged a platform for the mild production of aminium from either unfunctionalized or N-functionalized amines. This Perspective covers recent synthetic methods rely on photocatalytic formation, specifically context alkene hydroamination, arene C–H amination, mesolytic cleavage alkoxyamines.

Язык: Английский

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Diversification of pharmaceutical molecules via late-stage C(sp2)–H functionalization

Green Synthesis and Catalysis, Год журнала: 2023, Номер 4(2), С. 104 - 123

Опубликована: Янв. 2, 2023

C–H late-stage functionalization has gradually become a powerful approach for the rapid optimization of lead compounds' bioactivity. Significant advances in this field have been achieved past few years, mainly, system (hetero)aryl activation owing to importance moiety pharmaceutical. In review, we described selected recent examples how developed intermolecular C(sp2)–H methodologies involving diverse techniques diversify pharmaceutical molecules late stage.

Язык: Английский

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Site-Selective Electrochemical Arene C–H Amination

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(6), С. 3591 - 3597

Опубликована: Янв. 31, 2024

Here we present the discovery and development of a highly selective aromatic C–H amination reaction. This electrochemical strategy involves cathodic reduction process that generates electrophilic dicationic N-centered radicals can efficiently engage in functionalization channel regioselectivity substitution. The nitrogen-radical cation–pi interaction with arenes used throughout nature leads to charge transfer mechanism, subsequent C–N bond formation. aryl DABCOnium salts excellent yields regioselectivities (single regioisomer most cases). scope reaction on arene is broad where various functionalities such as halides (bromides, chlorides, fluorides), carbonyls (ketones, esters, imides), sulfonamides, heteroarenes (pyridines, bipyridines, terpyridines) are well tolerated. Moreover, disclose synthetic utility salt adducts leading direct access diverse piperazines chemoselective cleavage exocyclic C(sp2)–N over C(sp3)–N+ bonds via photoredox catalysis afford synthetically useful C–C C–P

Язык: Английский

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Visible-Light Photocatalytic C–H Amination of Arenes Utilizing Acridine–Lewis Acid Complexes

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(21), С. 14799 - 14806

Опубликована: Май 17, 2024

This report describes the development of a visible-light photocatalytic system for C(sp2)–H amination that leverages in situ-generated photocatalysts. We demonstrate combination acridine derivatives and Lewis acids forms potent photooxidants promote C–H electronically diverse arenes upon irradiation with (440 nm). A first-generation photocatalyst composed Sc(OTf)3 effects substrates oxidation potentials ≤ +2.5 V vs SCE pyrazole, triazole, pyridine nucleophiles. Furthermore, simplicity modularity this enable variation both acid to tune reactivity. enabled rapid identification two second-generation photocatalysts (derived from (i) Al(OTf)3 or (ii) pyridinium-substituted acridine) catalyze particularly challenging transformation: benzene as limiting reagent.

Язык: Английский

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Late stage C–H functionalization via chalcogen and pnictogen salts

Chemical Science, Год журнала: 2020, Номер 11(37), С. 10047 - 10060

Опубликована: Янв. 1, 2020

Late-stage functionalization (LSF) of heteroarenes can dramatically accelerate SAR studies by enabling the installation functional groups that would otherwise complicate a synthetic sequence. Although heteroaryl halides and boronic esters have well-established chemistries for LSF, alternatives enable site-selective C-H are highly attractive. Recently, three unrelated cationic (phosphonium, pyridinium, thianthrenium), which replace bonds late stage, been identified as precursors to various groups. This review will discuss synthesis application these salts with an emphasis on their use LSF medicinal chemistry.

Язык: Английский

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Synthesis of Phenol–Pyridinium Salts Enabled by Tandem Electron Donor–Acceptor Complexation and Iridium Photocatalysis

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(5), С. 3419 - 3429

Опубликована: Фев. 16, 2024

Herein, we describe a dual photocatalytic system to synthesize phenol–pyridinium salts using visible light. Utilizing both electron donor–acceptor (EDA) complex and iridium(III) cycles, the C–N cross-coupling of unprotected phenols pyridines proceeds in presence oxygen furnish pyridinium salts. Photocatalytic generation phenoxyl radical cations also enabled nucleophilic aromatic substitution (SNAr) fluorophenol with an electron-poor pyridine. Spectroscopic experiments were conducted probe mechanism reaction selectivity. The unique reactivity these displayed several derivatization reactions, providing rapid access diverse chemical space.

Язык: Английский

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