01869nas 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-alkenyl01434nas 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-indoles01871nas a2200289 4500008004100000022001400041245013600055210006900191260000900260300001600269490000700285520090000292653001901192653001901211653002001230653001201250653001401262653001101276653002301287100002801310700002901338700001801367700002401385700002601409700002001435856012601455 2021 eng d a2155-543500aNi(II)-catalyzed intramolecular C-H/C-H oxidative coupling: an efficient route to functionalized cycloindolones and indenoindolones0 aNiIIcatalyzed intramolecular CHCH oxidative coupling an efficien cOCT  a12384-123930 v113 aNickel(II)-catalyzed intramolecular C(sp(2))-H/C(sp(3))-H and C(sp(2))-H/C(sp(2))-H oxidative couplings in indoles are achieved via chelation assistance. These reactions provide access to biologically relevant five- and six-membered substituted cyclopentaindolones, carbazolones, and indenoindolones in high yields and good chemoselectivity employing an air-stable and defined nickel catalyst, (bpy)Ni(OAc)(2). The oxidative cyclizations proceeded either through a six-membered or an unconventional seven-membered nickelacycle. An extensive mechanistic investigation by experiments and theoretical calculations revealed a facile indole's C(2)-H nickelation and a rate-limiting reductive elimination process. This intramolecular oxidative cyclization operates via a probable Ni(II)/Ni(III) pathway involving single-electron oxidation of nickel without the participation of a carbon-based radical.10aC-H activation10acycloindolones10aindenoindolones10aindoles10aMechanism10aNickel10aoxidative coupling1 aAnkade, Shidheshwar, B.1 aSamal, Pragnya, Paramita1 aSoni, Vineeta1 aGonnade, Rajesh, G.1 aKrishnamurty, Sailaja1 aPunji, Benudhar uhttps://library.ncl.res.in/content/niii-catalyzed-intramolecular-c-hc-h-oxidative-coupling-efficient-route-functionalized01698nas 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-heterocycles02156nas a2200217 4500008004100000022001400041245012800055210006900183260000900252490000700261520138300268653001501651653002301666653001201689653001101701653002701712100002801739700002301767700002001790856012801810 2024 eng d a1434-193X00aNickel-catalyzed branch-selective C-H alkylation of indoles and azoles with alkenes: an additive- and solvent-free approach0 aNickelcatalyzed branchselective CH alkylation of indoles and azo cJUL 0 v273 a

The development of sustainable protocols for the synthesis of alkylated heteroarenes is crucial owing to their widespread existence in medicinally relevant and bioactive natural products. Herein, we describe an efficient, additive- and solvent-free approach for the regioselective C-H alkylation of indoles and azoles with alkenes using a nickel catalyst, which proceeds through a chelation-assistance strategy. The reaction exclusively provided branched alkylated products with the compatibility of alkyl, alkoxy, fluoro, trifluoromethyl, alkene, cyano, ester, and carbonyl groups. This protocol is applicable to other heteroarenes, such as imidazoles and benzimidazoles, providing the desired alkylated products with exclusive Markovnikov selectivity. The synthetic utility and scale-up of the reaction are demonstrated, and the protocol is in concord with the principles of green chemistry. Alkylation proceeds through facile and reversible C-H nickelation and alkene insertion processes, presumably involving rate-limiting reductive elimination. A straightforward nickel-catalyzed protocol for the C-H alkylation of indoles and azoles is disclosed that proceeds under additive- and solvent-free conditions. The reaction utilizes readily available alkenes as alkylating partners and delivers Markovnikov products with tolerance of sensitive functionalities. image

10aAlkylation10abranch selectivity10aindoles10aNickel10asolvent-free synthesis1 aAnkade, Shidheshwar, B.1 aBanerjee, Shuvajit1 aPunji, Benudhar uhttps://library.ncl.res.in/content/nickel-catalyzed-branch-selective-c-h-alkylation-indoles-and-azoles-alkenes-additive-and02021nas a2200217 4500008004100000022001400041245011000055210006900165260000800234490000700242520126500249653001901514653001201533653001401545653001901559653002601578100002601604700002401630700002001654856012901674 2025 eng d a1867-388000aPalladium-catalyzed regioselective C(4)-H fluoroalkoxylation of indoles through weak chelation assistance0 aPalladiumcatalyzed regioselective C4H fluoroalkoxylation of indo cJAN0 v173 a

Installing fluoroalkyl motifs into biorelevant indoles is particularly interesting due to their ubiquitous presence in drug molecules. Herein, we demonstrate the regioselective C4 fluoroalkoxylation of indoles using fluoroalcohols via palladium-catalyzed chelation-assisted C & horbar;H activation. The weak chelating benzoyl moiety at the C3 position acts as a directing group for remote C(4)& horbar;H fluoroalkoxylation of diversely substituted indoles. This methodology demonstrates a high level of regioselectivity and tolerates a range of crucial functional groups, yielding diverse trifluoroalkoxylated indoles in moderate to good yields. Removal of directing/protecting groups and further functionalization established the synthetic utility of the methodology. A preliminary mechanistic investigation is conducted by isolating the palladacycle intermediate and performing the deuterium scrambling study. The regioselective C4 fluoroalkoxylation of indoles with various fluoroalcohols is achieved by the palladium-catalyzed weak chelation assistance strategy. The reaction is compatible for a range of important functionalities and proceeds via the intermediacy of a six-membered palladacycle following a Pd(II)/Pd(IV) pathway. image

10aC-H activation10aindoles10aPalladium10aRegioselective10aTrifluoroalkoxylation1 aVijaykumar, Muniyappa1 aGonnade, Rajesh, G.1 aPunji, Benudhar uhttps://library.ncl.res.in/content/palladium-catalyzed-regioselective-c4-h-fluoroalkoxylation-indoles-through-weak-chelation