Photocatalytic Late-Stage C–H Functionalization

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(8), P. 4237 - 4352

Published: Jan. 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.

Language: Английский

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Radical-mediated rearrangements: past, present, and future

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(20), P. 11577 - 11613

Published: Jan. 1, 2021

This Review summarizes the past to present achievements in radical-mediated rearrangements, and brings up prospects that may inspire colleagues develop more useful synthetic tools based on radical rearrangements.

Language: Английский

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Visible‐Light‐Induced 1,3‐Aminopyridylation of [1.1.1]Propellane with N‐Aminopyridinium Salts

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(14), P. 7873 - 7879

Published: Jan. 7, 2021

Through the formation of an electron donor-acceptor (EDA) complex, strain-release aminopyridylation [1.1.1]propellane with N-aminopyridinium salts as bifunctional reagents enabled direct installation amino and pyridyl groups onto bicyclo[1.1.1]pentane (BCP) frameworks in absence external photocatalyst. The robustness this method to synthesize 1,3-aminopyridylated BCPs under mild metal-free conditions is highlighted by late-stage modification structurally complex biorelevant molecules. Moreover, strategy was extended P-centered CF3 radicals for unprecedented incorporation such functional pyridine across BCP core a three-component coupling. This practical lays foundation straightforward construction new valuable C4-pyridine-functionalized chemical entities, thus significantly expanding range accessibility BCP-type bioisosteres applications drug discovery.

Language: Английский

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N-Functionalized Pyridinium Salts: A New Chapter for Site-Selective Pyridine C–H Functionalization via Radical-Based Processes under Visible Light Irradiation

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(20), P. 3043 - 3056

Published: Sept. 27, 2022

ConspectusThe radical-mediated C–H functionalization of pyridines has attracted considerable attention as a powerful tool in synthetic chemistry for the direct bonds pyridine scaffold. Classically, methods functionalized often involve Minisci-type reactions under strongly acidic conditions. However, site-selective unbiased systems been long-standing challenge because scaffold contains multiple competing reaction sites (C2 vs C4) to intercept free radicals. Therefore, prefunctionalization is required avoid issues observed with formation mixture regioisomers and overalkylated side products.Recently, N-functionalized pyridinium salts have attracting organic promising radical precursors surrogates. The notable advantage lies their ability enhance reactivity selectivity synthetically useful acid-free This approach enables exquisite regiocontrol nonclassical at C2 C4 positions mild conditions, which are suitable late-stage bioactive molecules greater complexity diversity. Over past five years, variety fascinating applications developed using various types visible light In addition, new platform alkene difunctionalization appropriately designed N-substituted bifunctional reagents reported, offering an innovative assembly process complex architectures. Intriguingly, strategies involving light-absorbing electron donor–acceptor (EDA) complexes between electron-rich donors further open up photocatalyst-free Furthermore, we enantioselective afford enantioenriched bearing through single-electron N-heterocyclic carbene (NHC) catalysis.Herein, provide broad overview our recent contributions development summarize cornerstones that successfully employ these major advances field systematically categorized on basis pyridines' N-substituent, N–X (X = O, N, C, SO2CF3), its patterns. identification activation modes mechanistic aspects discussed by providing representative each paradigm. We hope this Account will inspire interest continued innovation exploration transformations.

Language: Английский

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Divergent reactivity of sulfinates with pyridinium salts based on one-versustwo-electron pathways

Chemical Science, Journal Year: 2021, Volume and Issue: 12(19), P. 6629 - 6637

Published: Jan. 1, 2021

Divergent reactions of sulfinates with pyridinium salts were developed by controlling the one-versustwo-electron reaction manifolds.

Language: Английский

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N-Amino pyridinium salts in organic synthesis

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(10), P. 2563 - 2580

Published: Jan. 1, 2023

This review summarizes the synthesis and reactivity of N -aminopyridinium salts, discusses applications in organic synthesis, highlights potential for these reagents to enable novel synthetic disconnections innovations.

Language: Английский

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Photoinduced difunctionalization with bifunctional reagents containing N-heteroaryl moieties

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(6), P. 1688 - 1700

Published: May 10, 2023

Language: Английский

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Electrochemical Asymmetric Radical Functionalization of Aldehydes Enabled by a Redox Shuttle

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(25)

Published: April 16, 2024

Aminocatalysis is a well-established tool that enables the production of enantioenriched compounds under mild conditions. Its versatility underscored by its seamless integration with various synthetic approaches. While combination aminocatalysis metal catalysis, photochemistry, and stoichiometric oxidants has been extensively explored, synergy electrochemical activation remains largely unexplored. Herein, we present successful merger electrochemistry to perform SOMO-type transformations, expanding toolkit for asymmetric synthesis. The methodology harnesses electricity drive oxidation catalytically generated enamines, which ultimately partake in enantioselective radical processes, leading α-alkylated aldehydes. Crucially, mechanistic studies highlight how this strategy enabled use redox shuttle, 4,4'-dimethoxybiphenyl, prevent catalyst degradation furnishing coveted good yield high enantioselectivity.

Language: Английский

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Photoredox-catalysed amidyl radical insertion to bicyclo[1.1.0]butanes

Nature Catalysis, Journal Year: 2024, Volume and Issue: 7(11), P. 1232 - 1242

Published: Oct. 22, 2024

Abstract Replacing planar aromatic rings in drug molecules with C( sp 3 )-rich isosteric mimetics, such as bicyclo[ n .1.1]alkanes, can significantly alter their physicochemical and pharmacokinetic properties, often leading to higher clinical success rates. However, unlike a benzene ring, the structurally rigid mimetics of heteroaromatic are rare. Heterobicyclo[ .1.1]alkanes promising this regard, but lack modular synthetic methods has currently hindered exploration. We envisioned that strategic selective insertion different heteroatomic units bicyclo[1.1.0]butanes could offer highly platform access diverse heterobicyclo[ .1.1]alkanes. Herein we report photoredox-catalysed regioselective chemoselective amidyl radicals bicyclo[1.1.0]butanes, providing direct 2-oxa-4-azabicyclo[3.1.1]hept-3-enes. The exit vector analysis shows geometric resemblance these heterobicyclic motifs pyridine pyrimidine derivatives, suggesting potential medicinally important heterocycles. Additionally, various downstream transformations demonstrate utility versatile building blocks chemistry.

Language: Английский

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Site‐Selective Pyridine C−H Alkylation with Alcohols and Thiols via Single‐Electron Transfer of Frustrated Lewis Pairs

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(51)

Published: Oct. 31, 2022

A unified strategy for the deoxygenative or desulfurative pyridylation of various alcohols and thiols has been developed through a single-electron transfer (SET) process frustrated Lewis pairs (FLPs) derived from pyridinium salts PtBu3 . Mechanistic studies revealed that N-amidopyridinium serve as effective acids formation FLPs with , generated phosphine radical cation ionically couples in situ xanthate, eventually affording alkyl facile β-scission under photocatalyst-free conditions. The reaction efficiency was further accelerated by visible-light irradiation. This method is conceptually appealing using encounter complexes FLP chemistry to promote SET, which provides previously unrecognized opportunity selective heteroarylation diverse range functional groups, even complex settings mild

Language: Английский

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