01752nas a2200253 4500008004100000022001400041245009500055210006900150260000800219300001500227490000700242520095900249653001901208653001701227653000901244653001101253653001401264653001401278100002201292700002201314700002401336700002001360856011801380 2022 eng d a1861-472800aEfficient route to 3,3 `-biindolinylidene-diones by iron-catalyzed dimerization of isatins0 aEfficient route to 33 biindolinylidenediones by ironcatalyzed di cAUG ae2022004140 v173 a

Iron-catalyzed dimerization of various isatin derivatives is described for the efficient synthesis of 3,3 `-biindolinylidene-diones (isoindigos). The reaction provides easy access to self-coupled and cross-coupled 3,3 `-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.

10aCross-coupling10adimerization10airon10aIsatin10aIsoindigo10aMechanism1 aJagtap, Rahul, A.1 aPradhan, Chandini1 aGonnade, Rajesh, G.1 aPunji, Benudhar uhttps://library.ncl.res.in/content/efficient-route-33-biindolinylidene-diones-iron-catalyzed-dimerization-isatins01698nas a2200241 4500008004100000022001400041245007700055210006900132260000800201300001200209490000700221520098000228653001501208653001101223653002601234653001701260653001201277653000901289653001401298100002201312700002001334856010201354 2023 eng d a0936-521400aAdvances in the iron-catalyzed direct functionalizations of heterocycles0 aAdvances in the ironcatalyzed direct functionalizations of heter cAPR a683-6970 v343 a

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

10aAlkylation10aazoles10aC-H functionalization10aheterocycles10aindoles10airon10aMechanism1 aPradhan, Chandini1 aPunji, Benudhar uhttps://library.ncl.res.in/content/advances-iron-catalyzed-direct-functionalizations-heterocycles02048nas a2200229 4500008004100000022001400041245010800055210006900163260000900232300001400241490000700255520125900262653002101521653001001542653002201552100002201574700002201596700002901618700002601647700002001673856012501693 2023 eng d a1463-926200aIron-catalyzed regioselective C-H alkylation of indoles: an additive-free approach in renewable solvent0 aIroncatalyzed regioselective CH alkylation of indoles an additiv cNOV  a9733-97430 v253 a

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'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.

10aAromatic Ketones10aGreen10aorganic synthesis1 aPradhan, Chandini1 aJagtap, Rahul, A.1 aSamal, Pragnya, Paramita1 aKrishnamurty, Sailaja1 aPunji, Benudhar uhttps://library.ncl.res.in/content/iron-catalyzed-regioselective-c-h-alkylation-indoles-additive-free-approach-renewable01289nas a2200181 4500008004100000022001400041245009300055210006900148260000800217300001400225490000700239520065100246100002600897700002200923700002400945700002000969856011800989 2023 eng d a1523-706000aPalladium-catalyzed chemoselective oxygenation of C(sp2)-H and C(sp3)-H bonds in isatins0 aPalladiumcatalyzed chemoselective oxygenation of Csp2H and Csp3H cMAR a1862-18670 v253 a

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.

1 aVijaykumar, Muniyappa1 aPradhan, Chandini1 aGonnade, Rajesh, G.1 aPunji, Benudhar uhttps://library.ncl.res.in/content/palladium-catalyzed-chemoselective-oxygenation-csp2-h-and-csp3-h-bonds-isatins01814nas a2200157 4500008004100000022001400041245011400055210006900169260000900238300001400247490000700261520121600268100002201484700002001506856013001526 2024 eng d a2052-412900aAdvancement in the C-H bond alkylation of (hetero)arenes catalyzed by the most abundant transition metal-iron0 aAdvancement in the CH bond alkylation of heteroarenes catalyzed  cAPR  a2397-24170 v113 a

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.

1 aPradhan, Chandini1 aPunji, Benudhar uhttps://library.ncl.res.in/content/advancement-c-h-bond-alkylation-heteroarenes-catalyzed-most-abundant-transition-metal-iron01350nas a2200181 4500008004100000022001400041245011500055210006900170260000900239300001600248490000700264520067400271100002600945700002200971700002400993700002001017856013101037 2024 eng d a1359-734500aChelation-assisted and steric-controlled selectivity in the Pd-catalyzed C-H/C-H oxidative coupling of indoles0 aChelationassisted and stericcontrolled selectivity in the Pdcata cNOV  a13028-130310 v603 a

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.

1 aVijaykumar, Muniyappa1 aPradhan, Chandini1 aGonnade, Rajesh, G.1 aPunji, Benudhar uhttps://library.ncl.res.in/content/chelation-assisted-and-steric-controlled-selectivity-pd-catalyzed-c-hc-h-oxidative-coupling01844nas a2200265 4500008004100000022001400041245012400055210006900179260000900248300001400257490000800271520093200279653001401211653000901225653001101234653002101245653004101266100002801307700002201335700002901357700002401386700002601410700002001436856012201456 2024 eng d a1615-415000aIron-catalyzed C-C and C-N bond-forming tandem amidation offering access to 3-amino-3-aminomethyl-2-oxindole frameworks0 aIroncatalyzed CC and CN bondforming tandem amidation offering ac cJUN  a2801-28100 v3663 a

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

10abenzamide10airon10aIsatin10atandem amidation10atetrasubstituted carbon stereocenter1 aAnkade, Shidheshwar, B.1 aPradhan, Chandini1 aSamal, Pragnya, Paramita1 aGonnade, Rajesh, G.1 aKrishnamurty, Sailaja1 aPunji, Benudhar uhttps://library.ncl.res.in/content/iron-catalyzed-c-c-and-c-n-bond-forming-tandem-amidation-offering-access-3-amino-301202nas a2200157 4500008004100000022001400041245010100055210006900156260000800225300001200233490000700245520062400252100002200876700002000898856012600918 2025 eng d a2374-794300aAtroposelective construction of biaryls enabled by a Ni(II)-catalyzed aerobic oxidation strategy0 aAtroposelective construction of biaryls enabled by a NiIIcatalyz cFEB a187-1890 v113 a

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

1 aPradhan, Chandini1 aPunji, Benudhar uhttps://library.ncl.res.in/content/atroposelective-construction-biaryls-enabled-niii-catalyzed-aerobic-oxidation-strategy02247nas a2200277 4500008004100000022001400041245012000055210006900175260000800244300001400252490000700266520131300273653002001586653002401606653002501630653001401655653001101669653001401680100002401694700002901718700002201747700002201769700002601791700002001817856013201837 2025 eng d a2155-543500aHybrid pincer (PNN)Ni(II) complex catalyzed selective C-H alkylation of pyridones using unactivated alkyl chlorides0 aHybrid pincer PNNNiII complex catalyzed selective CH alkylation  cFEB a2987-29990 v153 a

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.

10aalkyl chlorides10aC-H/C-Cl activation10ahybrid pincer ligand10aMechanism10aNickel10apyridones1 aVerma, Suryadev, K.1 aSamal, Pragnya, Paramita1 aPradhan, Chandini1 aPandey, Dilip, K.1 aKrishnamurty, Sailaja1 aPunji, Benudhar uhttps://library.ncl.res.in/content/hybrid-pincer-pnnniii-complex-catalyzed-selective-c-h-alkylation-pyridones-using-unactivated01378nas a2200217 4500008004100000022001400041245011200055210006900167260000800236490000700244520061700251653001600868653002300884653001100907653002500918653002100943100002200964700002200986700002001008856013201028 2025 eng d a1861-472800aRegioselective difluoroalkylation of 2-pyridones with fluoroalkyl bromides enabled by a nickel(II) catalyst0 aRegioselective difluoroalkylation of 2pyridones with fluoroalkyl cMAY0 v203 a

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.

10a2-pyridones10aDifluoroalkylation10aNickel10aradical intermediate10aRegioselectivity1 aPradhan, Chandini1 aKhandelwal, Disha1 aPunji, Benudhar uhttps://library.ncl.res.in/content/regioselective-difluoroalkylation-2-pyridones-fluoroalkyl-bromides-enabled-nickelii-catalyst02238nas a2200193 4500008004100000022001400041245013300055210006900188260000800257300001400265490000700279520150900286100002201795700002001817700002901837700002601866700002001892856013201912 2025 eng d a2044-475300asyn-Selective hydrosilylation and hydroboration of alkynes at room temperature catalyzed by a phosphine-free (NNN)Fe(ii) complex0 asynSelective hydrosilylation and hydroboration of alkynes at roo cNOV a6716-67250 v153 a

Catalytic hydrofunctionalization of alkynes is the ideal and atom-economical route to synthesize vinylsilanes and vinylboronates, which are valuable organic building blocks. However, the process suffers from using expensive phosphine-ligated catalysts, sensitive organometallic activators, and elevated reaction temperatures. To overcome these challenges, herein, we developed a series of phosphine-free (NNN)-ligated iron complexes and demonstrated their potential as efficient catalysts for the hydrosilylation and hydroboration of both internal and terminal alkynes using NaOtBu as an activator. The reactions proceeded smoothly using 1.5 mol% catalyst loading at room temperature and provided syn-selective vinylsilanes and vinylboronates. This hydrofunctionalization exclusively delivered mono-silylated and mono-borylated vinyls with tolerance of sensitive functionalities. At the same time, terminal alkynes provided excellent anti-Markovnikov selectivity with thermodynamically feasible beta-(E)-vinylsilanes and beta-(E)-vinylboronates. The presence of an N-H moiety in the ligand backbone is crucial in generating an Fe(ii) active catalyst and facilitating the catalytic process. Mechanistic investigations, including controlled reactions and external additive experiments, were performed to propose a redox-neutral reaction mechanism with iron maintaining its +2 oxidation state throughout the cycle. The DFT energy calculations unanimously support the proposed reaction mechanism.

1 aPradhan, Chandini1 aDubey, Shivansh1 aSamal, Pragnya, Paramita1 aKrishnamurty, Sailaja1 aPunji, Benudhar uhttps://library.ncl.res.in/content/syn-selective-hydrosilylation-and-hydroboration-alkynes-room-temperature-catalyzed-phosphine