@article {48083, title = {Efficient route to 3,3 {\textquoteleft}-biindolinylidene-diones by iron-catalyzed dimerization of isatins}, journal = {Chemistry-an Asian Journal}, volume = {17}, year = {2022}, month = {AUG}, pages = {e202200414}, type = {Article}, abstract = {

Iron-catalyzed dimerization of various isatin derivatives is described for the efficient synthesis of 3,3 {\textquoteleft}-biindolinylidene-diones (isoindigos). The reaction provides easy access to self-coupled and cross-coupled 3,3 {\textquoteleft}-indolinylidene-diones that have high relevance to biology and materials. This Fe(0)- or Fe(II)-catalyzed dimerization reaction tolerates a wide range of functionalities, such as fluoro, chloro, bromo, alkenyl, nitrile, ether, ester, pyrrolyl, indolyl and carbazolyl groups, including cyclic and acyclic alkyls as well as an alkyl-bearing fatty-alcohol moiety. Especially, the coupling between two distinct isatins provided excellent selectivity for the cross-dimerization with trace of self-couplings. The single-crystal X-ray diffraction study established the molecular structure of eight dimerized products. A preliminary mechanistic study of the Fe-catalyzed dimerization supported the radical pathway for the reaction.

}, keywords = {Cross-coupling, dimerization, iron, Isatin, Isoindigo, Mechanism}, issn = {1861-4728}, doi = {10.1002/asia.202200414}, author = {Jagtap, Rahul A. and Pradhan, Chandini and Gonnade, Rajesh G. and Punji, Benudhar} } @article {49125, title = {Advances in the iron-catalyzed direct functionalizations of heterocycles}, journal = {Synlett}, volume = {34}, year = {2023}, month = {APR}, pages = {683-697}, type = {Article}, abstract = {

Direct functionalization of heterocycles is an advanced strategy for diversifying privileged and biorelevant heterocycle-containing molecules. Particularly, use of the most abundant transition metal, iron, as a catalyst makes this process highly cost-effective and sustainable. Recently, some progress has been realized towards the direct functionalization of heterocycles under iron catalysis. Herein, we present the developments in the C-H bond functionalizations and related reactions of various heterocycles by abundant iron salts. This Synpacts is categorized into different sections based on heterocycles being functionalized, and each section is discussed based on the type of reaction catalyzed by iron. 1 Introduction 2 Functionalization of Indoles 2.1 Alkylation 2.2 Alkenylation 2.3 Other Reactions 3 Oxindoles and isatins 3.1 C-C Bond Formation 3.2 C-Heteroatom Bond Formation 4 Pyridines and Furans 5 Functionalization of Azoles 6 Summary and Outlook

}, keywords = {Alkylation, azoles, C-H functionalization, heterocycles, indoles, iron, Mechanism}, issn = {0936-5214}, doi = {10.1055/a-1890-8503}, author = {Pradhan, Chandini and Punji, Benudhar} } @article {48957, title = {Iron-catalyzed regioselective C-H alkylation of indoles: an additive-free approach in renewable solvent}, journal = {Green Chemistry }, volume = {25}, year = {2023}, month = {NOV }, pages = {9733-9743}, type = {Journal Article}, abstract = {

Alkylated indoles are important motifs in various biologically active molecules and drug candidates. Herein, we report a mild and efficient iron-catalyzed protocol for synthesizing alkylated indoles via C-H bond alkylation of indoles with unactivated alkenes, demonstrating a high level of regioselectivity. The reaction occurs under additive-free, solvent-free (or trace green solvent, 2-MeTHF) and less energy-intensive conditions using a sustainable metal catalyst and provides easy access to privileged alkylated indoles with anti-Markovnikov selectivity. Alkylation is compatible with important functionalities, such as fluoro, chloro, trifluoromethyl, alkenyl, ether, thioether, silyl, and siloxane, including heteroaryl, pyridinyl, carbazolyl, and indolyl moieties (45 examples, up to 96\% yield). The developed protocol is very simple, straightforward, and fully accords with the principles of green chemistry. A detailed mechanistic investigation manifests the facile indole{\textquoteright}s C-H activation at the Fe(0) center, reversible 1,2-insertion of the alkene into the Fe-H bond of a metallacycle, and a turnover-limiting reductive elimination. Alkylated indoles are important motifs in various biologically active molecules and drug candidates.

}, keywords = {Aromatic Ketones, Green, organic synthesis}, issn = {1463-9262}, doi = {10.1039/d3gc03709f}, author = {Pradhan, Chandini and Jagtap, Rahul A. and Samal, Pragnya Paramita and Krishnamurty, Sailaja and Punji, Benudhar} } @article {48270, title = {Palladium-catalyzed chemoselective oxygenation of C(sp2)-H and C(sp3)-H bonds in isatins}, journal = {Organic Letters}, volume = {25}, year = {2023}, month = {MAR}, pages = {1862-1867}, type = {Article}, abstract = {

The palladium-catalyzed chemoselective C(sp2)-H and C(sp3)-H bond oxygenation of substituted isatin derivatives is reported. This mild protocol exhibits the C5 C(sp2)-H oxygenation of isatins through electrophilic intermolecular C-H palladation in concentrated solutions using PhI(OAc)2 or Selectfluor as an oxidant, whereas it exhibits- N-CH3 C(sp3)-H oxygenation in dilute solutions via carbonyl-assisted intramolecular palladation in the presence of K2S2O8. This oxygenation reaction provides a direct and unified approach for synthesizing diverse oxygenated isatins with sensitive functionalities, including biorelevant compounds.

}, issn = {1523-7060}, doi = {10.1021/acs.orglett.3c00342}, author = {Vijaykumar, Muniyappa and Pradhan, Chandini and Gonnade, Rajesh G. and Punji, Benudhar} } @article {49020, title = {Advancement in the C-H bond alkylation of (hetero)arenes catalyzed by the most abundant transition metal-iron}, journal = {Organic Chemistry Frontiers }, volume = {11}, year = {2024}, month = {APR }, pages = {2397-2417}, type = {Review}, abstract = {

Alkylation reaction stands as a crucial organic transformation, fostering privileged alkylated arenes and heteroarenes in molecular science. Over the past decade, the utilization of the most abundant transition metal iron for regioselective C-H bond alkylation has gained substantial prominence, offering a straightforward and sustainable approach. Noteworthy progress has been achieved in the alkylation of diverse arenes and heteroarenes involving primary, secondary, and tertiary alkyl (pseudo)halide, alkene, and alcohol coupling partners via both the mono- and bidentate-chelate strategies. This concise and focused review provides an overview of the advancement in the iron-catalyzed alkylation of arenes and heteroarenes through step-economical C-H functionalization, their novel features, proposed mechanisms, and future research directions. The review is categorized into two major sections: (i) alkylation of arenes and (ii) alkylation of heteroarenes. Each section is discussed based on the class of arenes and heteroarenes used. Advancement in the direct C-H bond alkylation of arenes and heteroarenes using the catalysts based on the most abundant transition metal, iron, is summarized.

}, issn = {2052-4129}, doi = {10.1039/d4qo00063c}, author = {Pradhan, Chandini and Punji, Benudhar} } @article {49199, title = {Chelation-assisted and steric-controlled selectivity in the Pd-catalyzed C-H/C-H oxidative coupling of indoles}, journal = {Chemical Communications}, volume = {60}, year = {2024}, month = {NOV }, pages = {13028-13031}, type = {Article}, abstract = {

We report the first regioselective C2-C7 oxidative coupling of indoles using a palladium catalyst upon the strategic installation of N-pyridinyl and C3-carbonyl, which delivers 2,7-biindoles with a broad scope (25 examples; up to 93\% yield). Isolation of the catalytic intermediate reveals the initial activation of the C(7)-H bond, followed by the C(2)-H bond in indoles, and the reaction proceeds via a Pd(ii)/Pd(0) pathway. This manuscript describes the first regioselective C2-C7 oxidative coupling of indoles using a palladium catalyst through the strategic installation of N-pyridinyl and C3-carbonyl, which delivers diverse biorelevant 2-7-biindoles.

}, issn = {1359-7345}, doi = {10.1039/d4cc03835e}, author = {Vijaykumar, Muniyappa and Pradhan, Chandini and Gonnade, Rajesh G. and Punji, Benudhar} } @article {49366, title = {Iron-catalyzed C-C and C-N bond-forming tandem amidation offering access to 3-amino-3-aminomethyl-2-oxindole frameworks}, journal = {Advanced Synthesis \& Catalysis}, volume = {366}, year = {2024}, month = {JUN }, pages = {2801-2810}, type = {Article}, abstract = {

An iron-catalyzed protocol for the synthesis of 3-amino-3-aminomethyl-2-oxindole heterocyclic structures is disclosed employing isatins and non-nucleophilic N-methoxybenzamides. This reaction class is associated with broad scope and tolerates numerous functionalities, such as fluoro, chloro, bromo, iodo, trifluoromethyl, nitrile, ester, ether, and alkenyl, including heteroaryl - thiophene, benzothiophene, carbazolyl, indolyl, eugenol, and polycyclic cholesterol moieties. Detailed mechanistic investigations reveal that the reaction proceeds via iron-catalyzed N-O bond cleavage in N-methoxybenzamides, generating formaldehyde and benzamide, and through the intermediacy of isatin-ketimines and N-(hydroxymethyl)benzamides. Overall, this amidation reaction involves one C-C and two C-N bond-forming tandem processes, providing a range of beta-amino-aminomethyl-oxindoles (45 examples) in up to 88\% yields. image

}, keywords = {benzamide, iron, Isatin, tandem amidation, tetrasubstituted carbon stereocenter}, issn = {1615-4150}, doi = {10.1002/adsc.202400216}, author = {Ankade, Shidheshwar B. and Pradhan, Chandini and Samal, Pragnya Paramita and Gonnade, Rajesh G. and Krishnamurty, Sailaja and Punji, Benudhar} } @article {49490, title = {Atroposelective construction of biaryls enabled by a Ni(II)-catalyzed aerobic oxidation strategy}, journal = {ACS Central Science}, volume = {11}, year = {2025}, month = {FEB}, pages = {187-189}, type = {News Item}, abstract = {

Enantioriched biaryls synthesis via aerobic oxidative cross-coupling of arenes involving\ bioinspired oxygen activation by Ni(II).

}, issn = {2374-7943}, doi = {10.1021/acscentsci.5c00169}, author = {Pradhan, Chandini and Punji, Benudhar} } @article {49551, title = {Hybrid pincer (PNN)Ni(II) complex catalyzed selective C-H alkylation of pyridones using unactivated alkyl chlorides}, journal = {ACS Catalysis}, volume = {15}, year = {2025}, month = {FEB}, pages = {2987-2999}, type = {Article}, abstract = {

The use of readily accessible unactivated alkyl chlorides in the alkylation reaction to install valuable alkyl and methyl motifs into privileged heterocycles is an underdeveloped area. Herein, we report the regioselective C-H alkylation of diverse pyridones employing challenging unactivated alkyl chlorides as coupling partners, enabled by a strategically developed quinolinyl-based pincer (Ph2PNNQ)Ni(II) complex. The air-stable nickel catalyst is highly effective for the selective alkylation of functionalized 2-pyridones with both primary and secondary alkyl chlorides as well as for the unexpected C6 methylation, furnishing a wide range of 6-alkyl-2-pyridone scaffolds (78 examples). Remarkably, the alkyls bearing biologically and pharmacologically significant motifs, such as pterostilbene, nonyl phenol, sesamol, estrone, vitamin E, stigmasterol, cholesterol, and diosgenin, were compatible under this catalytic approach. The insights into the mechanism suggest that the alkylation reaction follows a Ni(II)/Ni(III)/Ni(IV) pathway involving the crucial two-step, one-electron oxidative addition of alkyl chloride. Several control studies, kinetics, and EPR analyses were performed to understand the detailed reaction pathway, further supported by density functional theory calculations.

}, keywords = {alkyl chlorides, C-H/C-Cl activation, hybrid pincer ligand, Mechanism, Nickel, pyridones}, issn = {2155-5435}, doi = {10.1021/acscatal.4c07173}, author = {Verma, Suryadev K. and Samal, Pragnya Paramita and Pradhan, Chandini and Pandey, Dilip K. and Krishnamurty, Sailaja and Punji, Benudhar} } @article {49698, title = {Regioselective difluoroalkylation of 2-pyridones with fluoroalkyl bromides enabled by a nickel(II) catalyst}, journal = {Chemistry-An Asian Journal}, volume = {20}, year = {2025}, month = {MAY}, type = {Article}, abstract = {

Regioselective C-H difluoroalkylation of diverse 2-pyridones with ethyl bromodifluoroacetates and bromodifluoroacetamides is accomplished by using a (dppf)NiCl2 catalyst under mild conditions. This efficient protocol could deliver a variety of C-3 difluoroalkylated pyridones with the tolerance of a range of highly susceptible functionalities, such as -Cl, -Br, -I, -COMe, -CN, -NMe2 and -NO2, including heteroarenes like pyridinyl, furanyl, thiophenyl and carbazolyl moieties. A preliminary mechanistic study suggests the radical pathway for the reaction involving fluoroalkyl radical intermediate.

}, keywords = {2-pyridones, Difluoroalkylation, Nickel, radical intermediate, Regioselectivity}, issn = {1861-4728}, doi = {10.1002/asia.202401870}, author = {Pradhan, Chandini and Khandelwal, Disha and Punji, Benudhar} }