C─H Functionalization of Heteroarenes via Electron Donor-Acceptor Complex Photoactivation.

C─H Functionalization of heteroarenes stands as a potent instrument in organic synthesis, and with the incorporation of visible light, it emerged as a transformative game-changer. In this domain, electron donor-acceptor (EDA) complex, formed through the pairing of an electron-rich substrate with an electron-accepting molecule, has garnered substantial consideration in recent years due to the related avoidance of the requirement of photocatalyst as well as oxidant. EDA complexes can undergo photoactivation under mild conditions and exhibit high functional group tolerance, making them potentially suitable for the functionalization of biologically relevant heteroarenes. This review article provides an overview of recent advancements in the field of C─H functionalization of heteroarenes via EDA complex photoactivation with literature coverage up to April, 2024.

Unusual Regioselective C-H Difluoroalkylation of Heteroarenes under Photoredox Catalysis.

We disclose a new general strategy for the site-selective difluoroalkylation of nonprefunctionalized heteroarenes, such as quinoxaline at the C-8 position, and benzothiadiazole, benzoxadiazole, and benzothiazole at the C-4 position via consecutive organophotoredox-catalyzed radical-radical cross-coupling and base-assisted hydrogen abstraction reactions. The current methodology represents a site-selective direct difluoroalkylative strategy to allow broad functional group tolerance and a wide substrate scope in good to excellent yields. Careful experimental investigations and detailed DFT calculations revealed the exact site-selectivity of the heteroarenes and a possible mechanistic pathway.

Hydro-phosphorothiolation of Styrene and Cyclopropane with S-Hydrogen Phosphorothioates under Ambient Conditions.

A metal-free hexafluoroisopropanol-mediated hydro-phosphorothiolation of styrenes and donor-acceptor cyclopropanes with S-hydrogen phosphorothioates in a Markovnikov fashion has been developed under ambient reaction conditions to afford a library of S-alkyl phosphorothioates. Notably, this strategy provides a simple and efficient way to produce biologically significant kitazin and iprobenfos derivatives. Mechanistic studies disclose that the reaction proceeds through a carbocation intermediate.

Site-selective direct nitration of 2H-indazoles: easy access to 7-nitroindazoles.

A new site-selective methodology for C-H nitration of 2H-indazoles has been accomplished at the C7 position using iron(III) nitrate. This strategy enables practical access to an array of 7-nitroindazoles with broad functional group tolerance in good yields. The synthesized products have been proven as valuable synthetic intermediates by demonstrating the synthetic utility. Mechanistic investigations indicate that the reaction goes through a radical pathway.

Iodine(III)-promoted oxidative carbotrifluoromethylation of maleimides with imidazopyridines and Langlois' reagent.

A metal-free protocol for oxidative carbotrifluoromethylation of maleimides with imidazopyridines and Langlois' reagent has been developed using (diacetoxyiodo)benzene (PIDA) as an oxidant. This three-component strategy enables one-step construction of 3,4-disubstituted maleimides in good yields with high functional group tolerance. Both experimental and theoretical studies support the proposed radical reaction mechanism.

Silylation of 2H-indazoles by photoinduced hydrogen atom transfer catalysis.

A metal-free, visible-light-mediated C-H silylation of 2H-indazoles with triphenylsilane has been developed employing 4CzIPN as a photocatalyst and triisopropylsilanethiol as a hydrogen atom transfer (HAT) reagent under aerobic reaction conditions. This method shows tolerance toward many functional groups and affords a variety of silylated indazoles at up to 89% yield. The experimental results suggest that the reaction progresses through a radical pathway.

One-Pot Manganese (I)-Catalyzed Oxidant-Controlled Divergent Functionalization of 2-Arylindazoles.

The oxidant-controlled divergent synthesis of C-2' formyl 2H-indazoles and indazoloindazolediones has been developed through Mn(I)- catalyzed ortho C-H functionalization of 2H-indazoles with para-formaldehyde to afford C-2' hydroxymethylated 2H-indazoles and subsequently oxidation with varying the amount of DDQ in one-pot. By employing selectfluor as the oxidant instead of DDQ, this reaction exclusively provided indazolebenzoxazine derivatives. This strategy delivered unsymmetrical indazoloindazoledione and indazolobenzoxazine with varied functional group tolerance in moderate to good yields.

Skeletal Editing through Molecular Recombination of 2H-Indazoles to Azo-Linked-Quinazolinones.

A new protocol by the combinatory use of two equivalent of indazoles starting material with one being the carbon source via its C3-reactivity and the other, the coupling partner has been developed for the selectfluor-mediated single atom skeletal editing of 2H-indazoles. The azo-linked-2,3-disubstituted quinazolin-4-one derivatives were obtained through a carbon atom insertion between the two nitrogens of the indazole ring and simultaneous oxidation at C3 position of both indazole moieties. Mechanistic investigations reveal that the amidic carbonyl oxygen of the product is derived from water and the reaction proceeds through in-situ generated N-centred indazolone radical intermediate.

An Electrochemical Oxo-amination of 2H-Indazoles: Synthesis of Symmetrical and Unsymmetrical Indazolylindazolones.

We have established a supporting-electrolyte free electrochemical method for the synthesis of indazolylindazolones through oxygen reduction reaction (eORR) induced 1,3-oxo-amination of 2H-indazoles where 2H-indazole is used as both aminating agent as well as the precursor of indazolone. Moreover, we have merged indazolone and indazole to get unsymmetrical indazolylindazolones through direct electrochemical cross-dehydrogenative coupling (CDC). This exogenous metal-, oxidant- and catalyst-free protocol delivered a number of multi-functionalized products with high tolerance of diverse functional groups.

Visible Light Induced Three-Component 1,2-Dicarbofunctionalization of Alkenes and Alkynes.

Harnessing visible-light in organic synthesis is one of the most effective methods that aligns with green and sustainable chemistry principles and hence skyrocketed in the last two decades. Similarly, three-component 1,2-dicarbofunctionalization of alkenes and alkynes has recently been a great choice to construct complex molecular systems in an easy and rapid manner. Therefore, light-induced reactions can be an excellent alternative to carry out 1,2-dicarbofunctionalization reactions, and very recently, organic chemists across the globe have fascinated us with their interesting articles. In this present review, we have summarized the recent advancements in the area of visible light induced three-component 1,2-dicarbofunctionalization of alkenes and alkynes till March 2023. We have categorized the discussion based on the catalysts used to carry out the transformations for better understanding and different important aspects of these transformations have also been covered.

Imino-λ3-iodane-Triggered Oxidative Ring-Opening of 2H-Indazoles to ortho-N-Acylsulfonamidated Azobenzenes.

An iminoiodane-enabled oxidative ring-opening of 2H-indazoles via C-N bond cleavage has been developed under metal-free reaction conditions. This methodology afforded a new array of unsymmetrical ortho-N-acylsulfonamidated azobenzenes with a wide functional group tolerance in good yields. The reaction potentially proceeds through the formation of a zwitterionic adduct, which is formed by the reaction between 2H-indazoles and iminoiodane.

Redox-neutral carbon-heteroatom bond formation under photoredox catalysis.

Recently, visible-light-mediated photoredox catalysis has been emerging as one of the fastest growing fields in organic chemistry because of its low cost, easy availability and environmental benignness. In the past five years, a new yet challenging trend, visible-light-induced redox-neutral carbon-heteroatom bond formation reaction involving presumed radical intermediates, has been flourishing rapidly. Although mostly transition metal-based photoredox catalysts were reported, a few organophotoredox catalysts have also shown efficacy towards carbon-heteroatom bond formation reactions. This review intends to summarize the recent research progress in redox-neutral carbon-heteroatom bond formations based on active intermediate(s) involved under photoredox catalysis.

Electrochemical C-H Sulfonylation of Hydrazones.

We have developed an electrochemical method for the direct C-H sulfonylation of aldehyde hydrazones using sodium sufinates as the sulfonylating agent under supporting electrolyte-free conditions. This straightforward sulfonylation strategy afforded a library of (E)-sufonylated hydrazones with high tolerance of various functional groups. The radical pathway of this reaction has been revealed by the mechanistic studies.

Visible-light-induced cascade reaction: a sustainable approach towards molecular complexity.

Photoredox catalysis has demonstrated rapid evolution in the field of synthetic organic chemistry. On the other hand, the splendour of cascade reactions in providing complex molecular architectures renders them a cutting-edge research area. Therefore, the merging of photocatalysis with cascade synthesis brings out a synthetic paradigm with immense potential. The development of photocascade catalysis for a target molecule with a particular molecular skeleton and stereochemical framework presents certain challenges but provides a robust and environmentally benign synthetic alternative. This comprehensive review assembles all the accomplishments and highlights of visible-light-induced cascade reactions with literature coverage up to October 2022.

Recent advances in carbosilylation of alkenes and alkynes.

Alkene and alkyne difunctionalization is a flexible process that allows the construction of two functional groups simultaneously in one step. On the other hand, carbosilylation, an ingenious difunctionalization pathway to concurrently incorporate both a silyl group and an organic functional group (alkyl, (hetero)aryl, alkenyl, alkynyl and allenyl) across a carbon-carbon multiple-bond system, is achieving immense interest in recent days. This review article provides a decade's update on the discoveries and developments in the synthesis of carbosilylated products from two very important carbon-carbon unsaturated substrates, alkenes and alkynes.

Visible-light-induced Mn(0)-catalyzed direct C-3 mono-, di- and perfluoroalkylation reactions of 2H-indazoles.

A general and efficient method for visible-light-driven fluoroalkylation, such as difluoromethylphosphonation, difluoroacetamidation, monofluoromethylation, difluoromethylation, and perfluoroalkyalation, of 2H-indazoles using an inexpensive Mn2(CO)10 photocatalyst has been developed. The present methodology affords a new series of C-3 fluoroalkylated 2H-indazole derivatives with wide functional group tolerance in good to excellent yields. Difluoromethylenated indiazoles are also prepared from difluoroester derivatives. Our mechanistic investigations support a radical pathway for the reaction.

Hypervalent iodine(III)-mediated oxidative dearomatization of 2H-indazoles towards indazolyl indazolones.

A new iodine(III)-mediated oxidative dearomatization of 2H-indazoles has been developed to afford N-1 indazolyl indazolones. In this methodology, PIFA plays a dual role: as an oxidant and as a carbonyl oxygen source. A series of indazolone derivatives was promptly synthesized in good to excellent yields through sequential C-heteroatom bond formation. Mechanistic studies indicate that the reaction likely takes place through an SET pathway.

Transition-metal-catalyzed ortho C-H functionalization of 2-arylquinoxalines.

Recently, direct C-H bond activation and functionalization has become a prodigious and hot topic among synthetic organic chemists due to its step-economic nature and substantial synthetic versatility. On the other hand, quinoxaline, a fused bicycle of benzene and pyrazine, has omnipresent applications in medicinal-, industrial- and materials chemistry. The presence of the N-1 atom in 2-arylquinoxaline enables chelation formation with a metal catalyst leading to the formation of ortho-substituted products. In this review, all articles related to the ortho C-H bond functionalization of 2-arylquinoxalines published up to May 2022 are highlighted.

Late-stage ortho-C-H alkenylation of 2-arylindazoles in aqueous medium by Manganese(i)-catalysis.

Earth-abundant and water-tolerant manganese(i) catalyzed alkenylation of 2-arylindazole with alkyl and aryl alkynes through C-H bond activation is described with a unique level of E-selectivity. The reaction proceeds through the control of C3 nucleophilicity of 2-aryl indazoles. This method is applied to the late-stage functionalization of complex molecules including ethinylestradiol, norethisterone, and N-protected amino acid derivatives. The kinetic isotope studies suggest that the C-H bond activation step may not be the rate-determining step.

Ortho C-H Functionalizations of 2-Aryl-2H-Indazoles.

C-H Functionalization is ubiquitously considered as a powerful, efficient and handy tool for installing various functional groups in complex organic heterocycles in an easier and step-economic way. Similarly, indazole is endowed as a potent heterocycle and is eminent for its profound impact in biological, medicinal and industrial chemistry. In this scenario, C-H functionalization at the selective ortho position of 2-arylindazole in assistance of a metal catalyst is also becoming an appealing approach in synthetic organic chemistry. This review addressed the recent findings and developments on ortho C-H functionalization of 2-aryl-2H-indazazoles with literature coverage extending from 2018 to May 2022.