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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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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Recent advances in difunctionalization of alkenes using pyridinium salts as radical precursors

Chemical Communications, Journal Year: 2022, Volume and Issue: 58(24), P. 3847 - 3864

Published: Jan. 1, 2022

This review summarises recent applications of pyridinium salts in radical-mediated difunctionalization alkenes. We hope this will provide a comprehensive overview topic and promote the wider development application salts.

Language: Английский

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Recent Advances in Electron Donor‐Acceptor (EDA)‐Complex Reactions involving Quaternary Pyridinium Derivatives

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(10), P. 1538 - 1564

Published: March 6, 2023

Abstract Quaternary pyridinium compounds are valuable intermediates in organic synthesis, which have gained immense popularity the synthetic community. The application of transition metal or photoredox catalysis transforming quaternary into various C−C and C−X bonds is well established. A majority these methods require high temperatures, expansive catalysts, delicate conditions for successful execution. On other hand, use metal‐free photocatalysis‐free strategies constructing using derivatives has been sought‐after. In this context, electron‐donor‐acceptor (EDA)‐complex reactions emerged as a state‐of‐the‐art methodology, do not any photocatalyst their EDA‐complex photochemistry takes advantage electron‐acceptor ability derivatives, can quickly generate radical precursor via deaminative process. These newly generated useful several transformations. We hereby, review, discuss an area major progress mediated involving with mechanism, substrate scope, limitations. magnified image

Language: Английский

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Practical and Regioselective Synthesis of C-4-Alkylated Pyridines

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(31), P. 11927 - 11933

Published: July 28, 2021

The direct position-selective C-4 alkylation of pyridines has been a long-standing challenge in heterocyclic chemistry, particularly from pyridine itself. Historically this addressed using prefunctionalized materials to avoid overalkylation and mixtures regioisomers. This study reports the invention simple maleate-derived blocking group for that enables exquisite control Minisci-type decarboxylative at allows inexpensive access these valuable building blocks. method is employed on variety different carboxylic acid alkyl donors, operationally scalable, applied known structures rapid fashion. Finally, work points an interesting strategic departure use Minisci chemistry earliest possible stage (native pyridine) rather than current dogma almost exclusively employs as late-stage functionalization technique.

Language: Английский

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

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 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.

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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Late‐Stage Functionalisation of Pyridine‐Containing Bioactive Molecules: Recent Strategies and Perspectives

European Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 26(16)

Published: Feb. 21, 2023

Abstract Late‐Stage Functionalisation (LSF) is an innovative technique that has been successfully applied to the C−H diversification of pharmaceuticals. However, LSF pyridine ring in drug‐like molecules often unselective. As a result, mixture structurally related products obtained, thus making purification tedious and time‐consuming. This review shines light on recent strategies addressing selectivity issue complex natural or drugs containing moiety. Specifically, we have reviewed efforts reported both academia industries with hope providing guide for elaborated pyridines.

Language: Английский

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Visible light-initiated manganese-catalyzed hydrosulfonylation of alkenes

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(10), P. 4122 - 4128

Published: Jan. 1, 2023

A visible light-initiated manganese-catalyzed radical hydrosulfonylation of a wide range structurally diverse alkenes using commercially available and relatively cheap sulfonyl chlorides as sources is described.

Language: Английский

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