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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Metal-Free Amino(hetero)arylation and Aminosulfonylation of Alkenes Enabled by Photoinduced Energy Transfer

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(30), P. 16630 - 16641

Published: July 24, 2023

β-(Hetero)arylethylamines are privileged structural motifs found in many high-value organic molecules, including pharmaceuticals and natural products. To construct these important molecular skeletons, previous methods mainly achieved by amino(hetero)arylation reaction with the aid of transition metals preactivated substrates. Herein, we report a metal-free photoinduced intermolecular for single-step installation both (hetero)aryl iminyl groups across alkenes an efficient regioselective manner. This method shows broad scope (up to 124 examples) excellent tolerance various olefins─from simplest ethylene complex multisubstituted can all participate reaction. Furthermore, aminosulfonylation be also conducted presence sodium bisulfite as SO2 source.

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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Photocatalytic Three-Component Reductive Coupling Synthesis of gem-Difluorohomoallyl Secondary Amines

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

gem-Difluorohomoallyl amines, an important class of gem-difluoroalkenes, are prevalent moieties in many bioactive compounds. However, limited methods suitable for the synthesis this type compound containing secondary amines. Here, we display a photocatalytic multicomponent protocol gem-difluoroalkenes which makes use readily available materials: arylamines, alkyl aldehydes, and α-trifluoromethyl alkenes. Moreover, ketones amines also substrates. Preliminary mechanistic experiments indicate that key α-amino radical was involved, generated from reduction situ-formed imines (or iminium ions) by reduced photocatalyst. Subsequent addition to alkenes β-F elimination deliver desired products.

Language: Английский

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Regioselective Access to Vicinal Diamines by Metal‐Free Photosensitized Amidylimination of Alkenes with Oxime Esters

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(44)

Published: Sept. 9, 2022

A metal-free photosensitized protocol for regioselective diamination of alkene feedstocks over a single step was developed based on the rationally designed bifunctional reagent, thus affording range differentially protected 1,2-diamines in moderate to high yields. Mechanistic studies reveal that reaction is initiated with triplet-triplet energy transfer between thioxanthone catalyst and followed by fragmentation simultaneously generate long-lived iminyl radical transient amidyl radical. The excellent regioselectivity presumably stems from large reactivity difference two different N-centered species. This characterized regioselectivity, broad functional group tolerance, mild conditions, which would enrich diversity versatility facilitate diversity-oriented synthesis 1,2-diamine-containing complex molecule scaffolds.

Language: Английский

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Electrophotocatalytic Reductive 1,2‐Diarylationof Alkenes with Aryl Halides and Cyanoaromatics

Chinese Journal of Chemistry, Journal Year: 2023, Volume and Issue: 41(16), P. 1921 - 1930

Published: April 7, 2023

Comprehensive Summary The radical‐mediated reductive functionalization of aryl halides has been extensively studied. However, the related intermolecular 1,2‐diarylation alkenes, using as radical sources, remains unexplored. Herein, a new electrophotocatalytic alkenes is reported and cyanoaromatics to produce polyarylated alkanes. Using synergistic cathodic reduction visible‐light photoredox catalysis, various electron‐rich electron‐deficient are combined with characterize broad substrate scope, excellent functional group compatibility, selectivity this reaction. Mechanistic investigations reveal that reaction may proceed via process initiated by generation radicals from terminated radical‐radical coupling cyanoaromatic anions.

Language: Английский

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Electrophotocatalytic tri- or difluoromethylative cyclization of alkenes

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(10), P. 2482 - 2490

Published: Jan. 1, 2023

Photoelectrocatalysis is mild yet potent and this work unlocks the potential of unactivated alkenes for oxidant-free oxidative cyclization alkenes.

Language: Английский

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Photocatalytic 1,2-Iminosulfonylation and Remote 1,6-Iminosulfonylation of Olefins

Organic Letters, Journal Year: 2023, Volume and Issue: 25(10), P. 1742 - 1747

Published: March 8, 2023

A new class of iminosulfonylation reagents were developed and extensively used in the 1,2-iminosulfonylation various olefins. Olefins containing bioactive molecules, such as indomethacin, gemfibrozil, clofibrate, fenbufen, afforded desired products synthetically useful yields. Furthermore, first remote 1,6-iminosulfonylation alkenes was realized by using oxime ester bifunctionalization reagents. Overall, more than 40 structurally diverse β-imine sulfones obtained moderate to excellent

Language: Английский

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Photochemical and Atom-Economical Sulfonylimination of Alkenes with Bifunctional N-Sulfonyl Ketimine

Organic Letters, Journal Year: 2023, Volume and Issue: 25(13), P. 2349 - 2354

Published: March 27, 2023

An organo-photocatalytic sulfonylimination of alkenes was developed by employing readily available N-sulfonyl ketimines as bifunctional reagents. This transformation, featuring prominent functional group tolerance, provides a direct and atom-economic approach for the synthesis valuable β-amino sulfone derivatives single regioisomer. In addition to terminal alkenes, internal participate in this reaction with high diastereoselectivity. N-Sulfonyl aryl or alkyl substituents were found be compatible condition. method could applied late-stage modifications drugs. Additionally, formal insertion alkene into cyclic sulfonyl imine observed, affording ring expansion product.

Language: Английский

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Three-Component Photochemical 1,2,5-Trifunctionalizations of Alkenes toward Densely Functionalized Lynchpins

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(43), P. 23814 - 23823

Published: Oct. 18, 2023

Radical remote 1,n-difunctionalization reactions (n > 2) of alkenes are powerful tools to efficiently introduce functional groups with selected distances into target molecules. Among these reactions, 1,5-difunctionalizations an important subclass, leading sought-after scaffolds, but typically suffer from tailored starting materials and strict limitations for the formed group in 2-position. Seeking address issues make radical more applicable, we report a novel three-component 1,2,5-trifunctionalization reaction between imine-based bifunctional reagents two distinct alkenes, driven by visible light energy transfer-catalysis. Key achieving this selective one-step installation three different via choreographed formation four bonds was utilization 1,2-boron shift rigorous capitalization polarities stabilities. Thorough mechanistic studies were carried out, synthetic utility obtained products demonstrated various downstream modifications. Notably, addition functionalization individual groups, their interplay gave rise unique array cyclic products.

Language: Английский

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