02017nas a2200193 4500008004100000245014400041210006900185260000800254300001400262490000700276520128500283100002401568700002201592700002301614700002401637700001701661700002001678856012501698 2016 eng d00aMechanistic insights into pincer-ligated palladium-catalyzed arylation of azoles with aryl Iodides: evidence of a Pd-II-Pd-IV-Pd-II pathway0 aMechanistic insights into pincerligated palladiumcatalyzed aryla cMAR a875–8860 v353 a

Pincer-based (R2POCNR′2)PdCl complexes along with CuI cocatalyst catalyze the arylation of azoles with aryl iodides to give the 2-arylated azole products. Herein, we report an extensive mechanistic investigation for the direct arylation of azoles involving a well-defined and highly efficient (iPr2POCNEt2)PdCl (2a) catalyst, which emphasizes a rare PdII–PdIV–PdII redox catalytic pathway. Kinetic studies and deuterium labeling experiments indicate that the C–H bond cleavage on azoles occurs via two distinct routes in a reversible manner. Controlled reactivity of the catalyst 2a underlines the iodo derivative (iPr2POCNEt2)PdI (3a) to be the resting state of the catalyst. The intermediate species (iPr2POCNEt2)Pd-benzothiazolyl (4a) has been isolated and structurally characterized. A determination of reaction rates of compound 4a with electronically different aryl iodides has revealed the kinetic significance of the oxidative addition of the C(sp2)–X electrophile, aryl iodide, to complex 4a. Furthermore, the reactivity behavior of 4a suggests that the arylation of benzothiazole proceeds via an oxidative addition/reductive elimination pathway involving a (iPr2POCNEt2)PdIV(benzothiazolyl)(Ar)I species, which is strongly supported by DFT calculations.

1 aKhake, Shrikant, M.1 aJagtap, Rahul, A.1 aDangat, Yuvraj, B.1 aGonnade, Rajesh, G.1 aVanka, Kumar1 aPunji, Benudhar uhttps://library.ncl.res.in/content/mechanistic-insights-pincer-ligated-palladium-catalyzed-arylation-azoles-aryl-iodides01372nas a2200169 4500008004100000245009700041210006900138260000800207300001600215490000600231520075600237100001800993700002201011700002401033700002001057856012501077 2016 eng d00aUnified strategy for nickel-catalyzed C-2 Alkylation of indoles through chelation assistance0 aUnified strategy for nickelcatalyzed C2 Alkylation of indoles th cJUL a5666–56720 v63 a

A nickel-catalyzed direct C-2 alkylation of indoles through monodentate-chelation assistance has been described. This reaction proceeds via an unusual strategy by the use of a well-designed and defined (quinolinyl)amido–nickel catalyst, [{κN,κN,κN-Et2NCH2C(O)(μ-N)C9H6N}Ni(OAc)], providing a solution to the limitations associated with bidentate-chelate auxiliaries. The method allows coupling of indoles with various unactivated primary and secondary alkyl halides with ample substrate scope. This uniquely strategized alkylation proceeded through crucial C–H activation and via an alkyl radical intermediate. The reaction by this approach represents a rare example of Ni-catalyzed monodentate-chelate-assisted C–H functionalization.

1 aSoni, Vineeta1 aJagtap, Rahul, A.1 aGonnade, Rajesh, G.1 aPunji, Benudhar uhttps://library.ncl.res.in/content/unified-strategy-nickel-catalyzed-c-2-alkylation-indoles-through-chelation-assistance01354nas a2200157 4500008004100000245008800041210007100129260000800200300001400208490000700222520078100229100002201010700001801032700002001050856012601070 2017 eng d00aExpeditious and solvent-free nickel-catalyzed C−H arylation of arenes and indoles0 aExpeditious and solventfree nickelcatalyzed C−H arylation of are cAPR a2242-22480 v103 aAn efficient solvent-free nickel-catalyzed method for C−H bond arylation of arenes and indoles has been developed, which proceeds expeditiously through chelation assistance. The reaction is highly selective for mono-arylation and tolerates sensitive and structurally diverse functionalities, such as halides, ethers, amines, indole, pyrrole and carbazole. This reaction represents the first example of a nickel-catalyzed C−H arylation by monochelate assistance and symbolizes a rare precedent in solvent-free C−H arylation. Mechanistic investigations by various controlled reactions, kinetic studies, and deuterium labeling experiments suggest that the arylation follows a single electron transfer (SET) pathway involving the turnover-limiting C−H nickelation process.1 aJagtap, Rahul, A.1 aSoni, Vineeta1 aPunji, Benudhar uhttps://library.ncl.res.in/content/expeditious-and-solvent-free-nickel-catalyzed-c%E2%88%92h-arylation-arenes-and-indoles01433nas a2200181 4500008004100000022001400041245007000055210006800125260000800193520083500201653002401036653002601060653001101086653001301097100002201110700002001132856009901152 2019 eng d a2193-580700aC-H functionalization of indoles by 3d transition-metal catalysis0 aCH functionalization of indoles by 3d transitionmetal catalysis cDEC3 a

Over the past decade, the use of 3d transition metal for the regioselective C-H bond functionalization of indoles has significantly increased. Particularly, advances in manganese, iron, cobalt, nickel and copper catalysis have demonstrated the selective C(2)-H and C(3)-H arylation, alkenylation, alkynylation and alkylation to a greater extent. Similarly, the C-O and C-N bond-forming reactions are manifested via direct C-H bond activation by these earth-abundant metals. The emergence of 3d metals in selective functionalization of the biologically relevant indoles and related heteroarenes would make this protocol more attractive for practical applications. Herein, we provide a brief overview of 3d transition metal-catalyzed (mostly Mn, Fe, Co, Ni and Cu) C-H functionalization of indoles and related heteroarenes.

10a3d transition metal10aC-H functionalization10aIndole10aindoline1 aJagtap, Rahul, A.1 aPunji, Benudhar uhttps://library.ncl.res.in/content/c-h-functionalization-indoles-3d-transition-metal-catalysis01869nas a2200241 4500008004100000022001400041245013600055210006900191260000800260300001200268490000600280520105500286653001701341653001901358653001201377653001401389653001101403653002901414100002201443700001801465700002001483856012401503 2019 eng d a2155-543500aNickel-catalyzed straightforward and regioselective C-H alkenylation of indoles with alkenyl bromides: scope and mechanistic aspect0 aNickelcatalyzed straightforward and regioselective CH alkenylati cJAN a431-4410 v93 a

Nickel-catalyzed regioselective C-H bond alkenylation of indoles and related heteroarenes with alkenyl bromides is accomplished under relatively mild conditions. This method allows the straightforward synthesis of C-2 alkenylated indoles employing an air-stable and well-defined nickel catalyst, (bpy)NiBr2, providing a solution to the limitations associated with hydroindolation and oxidative alkenylation. The reaction conceded the coupling of indole derivatives with various alkenyl bromides, such as aromatic and heteroaromatics, alpha- and beta-substituted as well as exo- and endo-cyclic alkenyl compounds. An extensive mechanistic investigation, including controlled study, reactivity experiments, kinetics and labeling studies, and EPR and XPS analyses, highlights that the alkenylation proceeds through a single-electron transfer process comprising an odd-electron oxidative addition of alkenyl bromide. Furthermore, the alkenylation operates via a probable Ni(I)/Ni(III) pathway involving the rate-limiting C-H nickelation of indole.

10aalkenylation10aC-H activation10aindoles10aMechanism10aNickel10asingle-electron transfer1 aJagtap, Rahul, A.1 aVinod, C., P.1 aPunji, Benudhar uhttps://library.ncl.res.in/content/nickel-catalyzed-straightforward-and-regioselective-c-h-alkenylation-indoles-alkenyl01578nas a2200169 4500008004100000022001400041245012400055210006900179260000900248300001400257490000700271520093500278100002101213700002201234700002001256856013201276 2019 eng d a0276-733300aScope and mechanistic aspect of nickel-catalyzed alkenylation of benzothiazoles and related azoles with styryl bromides0 aScope and mechanistic aspect of nickelcatalyzed alkenylation of  cJUN  a2422-24300 v383 a

Alkenylation of benzothiazoles and related azoles with alkenyl bromides is achieved employing the well-defined and air-stable nickel complexes, (bpy)NiBr2 and [Ni(bpy)(3)] [NiBr4], as catalysts. Numerous electronically distinct alkenyl bromides efficiently coupled with substituted benzothiazoles, oxazoles, and benzimidazoles under the catalytic conditions to afford 2-alkenylated azoles. An extensive mechanistic study of the alkenylation of benzothiazole using (bpy)NiBr2 highlights a single-electron transfer process for the reaction involving the two-step one-electron oxidative addition of alkenyl bromide. The substrate benzothiazole plays a significant and diverse role in the reaction, and C-H bond cleavage is reversible in nature. Detailed kinetic analysis and control reactivity studies are indicative of a Ni(I)/Ni(III) pathway for the alkenylation comprising the rate-influencing reductive elimination step.

1 aPatel, Ulhas, N.1 aJagtap, Rahul, A.1 aPunji, Benudhar uhttps://library.ncl.res.in/content/scope-and-mechanistic-aspect-nickel-catalyzed-alkenylation-benzothiazoles-and-related-azoles00752nas a2200217 4500008004100000022001400041245011000055210006900165260000900234300000900243490000700252653001400259653001900273653001700292653002600309653001100335100002200346700001800368700002000386856012800406 2020 eng d a1864-563100aExpeditious and solvent-free nickel-catalyzed c-h arylation of arenes and indoles (vol 10, pg 2242, 2017)0 aExpeditious and solventfree nickelcatalyzed ch arylation of aren cNOV  a57710 v1310aArylation10aC-H activation10aheterocycles10aHomogeneous catalysis10aNickel1 aJagtap, Rahul, A.1 aSoni, Vineeta1 aPunji, Benudhar uhttps://library.ncl.res.in/content/expeditious-and-solvent-free-nickel-catalyzed-c-h-arylation-arenes-and-indoles-vol-10-pg02123nas a2200265 4500008004100000022001400041245013800055210006900193260000900262300001400271490000700285520121800292653002001510653001501530653001901545653002501564653001401589653000901603100002201612700002901634700001801663700002601681700002001707856013001727 2020 eng d a2155-543500aIron-catalyzed C(sp(2))-H alkylation of indolines and benzo[h]quinoline with unactivated alkyl chlorides through chelation assistance0 aIroncatalyzed Csp2H alkylation of indolines and benzohquinoline  cJUL  a7312-73210 v103 a

Regioselective C-H bond alkylation of indolines and benzo[h]quinoline with a wide range of unactivated and highly demanded primary and secondary alkyl chlorides is accomplished using a low-cost iron catalyst. This reaction tolerates diverse functionalities, such as C(sp(2))-Cl, fluoro, alkenyl, silyl, ether, thioether, pyrrolyl, and carbazolyl groups including cyclic and acyclic alkyls as well as alkyl-bearing fatty-alcohol and polycyclic-steroid moieties. The demonstrated iron-catalyzed protocol proceeded via either a five-membered or a six-membered metallacycle. Intriguingly, the C-7-alkylated indolines can be readily functionalized into free-NH indolines/indoles and tryptamine derivatives. A detailed mechanistic investigation highlights the participation of an active Fe(I) catalyst and the involvement of a halogen-atom transfer process via a single-electron-based mechanism. Deuterium labeling and kinetics analysis indicate that the C-H metalation of indoline is the probable turnover-limiting step. Overall, the experimental and theoretical studies supported an Fe(I)/Fe(III) pathway for the alkylation reaction comprising the two-step, one-electron oxidative addition of alkyl chloride.

10aalkyl chlorides10aAlkylation10aC-H activation10achelation assistance10aindolines10airon1 aJagtap, Rahul, A.1 aSamal, Pragnya, Paramita1 aVinod, C., P.1 aKrishnamurty, Sailaja1 aPunji, Benudhar uhttps://library.ncl.res.in/content/iron-catalyzed-csp2-h-alkylation-indolines-and-benzohquinoline-unactivated-alkyl-chlorides01203nas a2200169 4500008004100000022001400041245009000055210006900145260000800214300001400222490000700236520060400243100002200847700002400869700002000893856012000913 2020 eng d a1523-706000aMnBr2-catalyzed direct and site-selective alkylation of indoles and benzo[h]quinoline0 aMnBr2catalyzed direct and siteselective alkylation of indoles an cJUN a4643-46470 v223 a

Manganese-catalyzed regioselective C-H alkylation of indoles and benzo[h]quinoline with a variety of unactivated alkyl iodides is reported. Unlike other Mn-catalyzed C-H functionalization, this protocol does not require a Grignard reagent base and employs a simple and inexpensive MnBr2 as a catalyst. This method tolerates diverse functionalities, including fluoro, chloro, bromo, iodo, alkenyl, alkynyl, pyrrolyl, and carbazolyl groups. The alkylation proceeds through a single-electron transfer pathway comprising reversible C-H manganesation and involving an alkyl radical intermediate.

1 aJagtap, Rahul, A.1 aVerma, Suryadev, K.1 aPunji, Benudhar uhttps://library.ncl.res.in/content/mnbr2-catalyzed-direct-and-site-selective-alkylation-indoles-and-benzohquinoline01840nas a2200181 4500008004100000022001400041245012700055210006900182260000800251300001600259490000700275520115400282100002201436700002801458700002401486700002001510856012801530 2021 eng d a1144-054600aAchiral and chiral NNN-pincer nickel complexes with oxazolinyl backbones: application in transfer hydrogenation of ketones0 aAchiral and chiral NNNpincer nickel complexes with oxazolinyl ba cJUL a11927-119360 v453 aWe describe the synthesis of new NNN-oxazolinyl-pincer nickel complexes and their application in the transfer hydrogenation of ketones. Achiral NNN-ligands, R `(2)-oxazolinyl-2-C6H4-NH-C(O)CH2NEt2 [((R ` 2-OxNNNEt2))-H; R' = H (3a), R ` = Me (3b)], and chiral ligands, (R)-R `-oxazolinyl-2-C6H4-NH-C(O)CH2NEt2 [(R)-((R `-OxNNNEt2))-H; R ` = Ph (3c), R ` = CH2Ph (3d), R ` = Pr-i (3e), R ` = (CH2Pr)-Pr-i (3f)], were efficiently synthesized. Treatment of these ligands with (DME)NiCl2 afforded the desired amido-pincer nickel complexes, ((R ` 2-OxNNNEt2))NiCl [R ` = H (4a), R ` = Me (4b)] and ((R `-OxNNNEt2))NiCl [R ` = Ph (4c), R ` = CH2Ph (4d), R ` = Pr-i (4e), R ` = (CH2Pr)-Pr-i (4f)], in good yields. All the ligand precursors and nickel complexes were thoroughly characterized by various analytical techniques. The molecular structures of 4a, 4d and 4f were established by X-ray crystallography. The developed nickel complexes were found to be efficient catalysts for the transfer hydrogenation of ketones using (PrOH)-Pr-i as a viable hydrogen source. Enantioselectivity in hydrogenation was not observed with the developed chiral catalysts.1 aJagtap, Rahul, A.1 aAnkade, Shidheshwar, B.1 aGonnade, Rajesh, G.1 aPunji, Benudhar uhttps://library.ncl.res.in/content/achiral-and-chiral-nnn-pincer-nickel-complexes-oxazolinyl-backbones-application-transfer01434nas a2200217 4500008004100000022001400041245007000055210006800125260000800193300001400201490000700215520076700222653001100989653002301000653002601023653001201049653001101061100002201072700002001094856010201114 2021 eng d a1527-899900aNickel-catalyzed C-H bond functionalization of azoles and indoles0 aNickelcatalyzed CH bond functionalization of azoles and indoles cDEC a3573-35880 v213 a

Direct C-H functionalization of privileged and biologically relevant azoles and indoles represents an important chemical transformation in molecular science. Despite significant progress in the palladium-catalyzed regioselective C-H functionalization of azoles and indoles, the use of abundant and less expensive nickel catalyst is underdeveloped. In the recent past, the nickel-catalyzed regioselective C-H alkylation, arylation, alkenylation and alkynylation of azoles and indoles have been substantially explored, which can be applied to the complex organic molecule synthesis. In this Account, we summarize the developments in nickel-catalyzed regioselective functionalization of azoles and indoles with a considerable focus on the reaction mechanism.

10aazoles10aC-C Bond formation10aC-H functionalization10aindoles10aNickel1 aJagtap, Rahul, A.1 aPunji, Benudhar uhttps://library.ncl.res.in/content/nickel-catalyzed-c-h-bond-functionalization-azoles-and-indoles01752nas 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-isatins02048nas 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-renewable