01294nas a2200157 4500008004100000245010200041210006900143260000800212300001400220490000700234520070900241100001800950700002300968700002000991856012501011 2018 eng d00a Nickel-catalyzed regioselective C(2)-H difluoroalkylation of indoles with difluoroalkyl bromides0 aNickelcatalyzed regioselective C2H difluoroalkylation of indoles cSEP a2516-25210 v133 aRegioselective C(2)-H difluoroalkylation of C-3 unsubstituted indoles with commonly available fluoroalkyl bromides is successfully achieved employing a simple nickel catalyst system, (DME)NiCl2/Xantphos. This methodology shows excellent regioselectivity and exhibits a broad substrate scope. Various functional groups, such as -OMe, -F, and -Br, are tolerated on the indole backbone to give the difluoroalkylated products in moderate to good yields. Preliminary mechanistic findings demonstrate that the reaction is homogeneous in nature and involves a radical manifold. Synthetic utility of this nickel-catalyzed method is demonstrated by synthesizing melatonin receptor antagonist Luzindole derivative.1 aSoni, Vineeta1 aSharma, Dipesh, M.1 aPunji, Benudhar uhttp://library.ncl.res.in/content/nickel-catalyzed-regioselective-c2-h-difluoroalkylation-indoles-difluoroalkyl-bromides01257nas a2200169 4500008004100000022001400041245009100055210006900146260000800215300001600223490000700239520065800246100002200904700002600926700002000952856011500972 2019 eng d a0022-326300aNickel-catalyzed C(2)-H arylation of indoles with aryl chlorides under neat conditions0 aNickelcatalyzed C2H arylation of indoles with aryl chlorides und cOCT a12800-128080 v843 a

Nickel-catalyzed regioselective C(2)-H arylation of indoles and pyrroles with aryl chlorides is achieved under neat conditions. This method allows the efficient coupling of diverse aryl chlorides employing a user-friendly and inexpensive Ni(OAc)(2)/dppf catalyst system at 80 degrees C. Numerous functionalities, such as halides, alkyl ether, fluoro-alkyl ether, and thioether, and substituted amines, including heteroarenes like benzothiazolyl, pyrrolyl, indolyl, and carbazolyl, are well tolerated under the reaction conditions. The preliminary mechanistic study highlights a single-electron transfer (SET) pathway for the arylation reaction.

1 aPandey, Dilip, K.1 aVijaykumar, Muniyappa1 aPunji, Benudhar uhttp://library.ncl.res.in/content/nickel-catalyzed-c2-h-arylation-indoles-aryl-chlorides-under-neat-conditions01465nas a2200193 4500008004100000022001400041245011700055210006900172260000800241300001400249490000700263520077500270100002201045700002801067700001401095700001801109700002001127856012401147 2019 eng d a2041-652000aNickel-catalyzed C-H alkylation of indoles with unactivated alkyl chlorides: evidence of a Ni(i)/Ni(iii) pathway0 aNickelcatalyzed CH alkylation of indoles with unactivated alkyl  cNOV a9493-95000 v103 a

A mild and efficient nickel-catalyzed method for the coupling of unactivated primary and secondary alkyl chlorides with the C-H bond of indoles and pyrroles is described which demonstrates a high level of chemo and regioselectivity. The reaction tolerates numerous functionalities, such as halide, alkenyl, alkynyl, ether, thioether, furanyl, pyrrolyl, indolyl and carbazolyl groups including acyclic and cyclic alkyls under the reaction conditions. Mechanistic investigation highlights that the alkylation proceeds through a single-electron transfer (SET) process with Ni(i)-species being the active catalyst. Overall, the alkylation follows a Ni(i)/Ni(iii) pathway involving the rate-influencing two-step single-electron oxidative addition of alkyl chlorides.

1 aPandey, Dilip, K.1 aAnkade, Shidheshwar, B.1 aAli, Abad1 aVinod, C., P.1 aPunji, Benudhar uhttp://library.ncl.res.in/content/nickel-catalyzed-c-h-alkylation-indoles-unactivated-alkyl-chlorides-evidence-niiniiii01868nas a2200241 4500008004100000022001400041245013600055210006900191260000800260300001200268490000600280520105500286653001701341653001901358653001201377653001401389653001101403653002901414100002201443700001801465700002001483856012301503 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 uhttp://library.ncl.res.in/content/nickel-catalyzed-straightforward-and-regioselective-c-h-alkenylation-indoles-alkenyl01433nas a2200217 4500008004100000022001400041245007000055210006800125260000800193300001400201490000700215520076700222653001100989653002301000653002601023653001201049653001101061100002201072700002001094856010101114 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 uhttp://library.ncl.res.in/content/nickel-catalyzed-c-h-bond-functionalization-azoles-and-indoles01870nas a2200289 4500008004100000022001400041245013600055210006900191260000900260300001600269490000700285520090000292653001901192653001901211653002001230653001201250653001401262653001101276653002301287100002801310700002901338700001801367700002401385700002601409700002001435856012501455 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 uhttp://library.ncl.res.in/content/niii-catalyzed-intramolecular-c-hc-h-oxidative-coupling-efficient-route-functionalized02155nas a2200217 4500008004100000022001400041245012800055210006900183260000900252490000700261520138300268653001501651653002301666653001201689653001101701653002701712100002801739700002301767700002001790856012701810 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 uhttp://library.ncl.res.in/content/nickel-catalyzed-branch-selective-c-h-alkylation-indoles-and-azoles-alkenes-additive-and02046nas a2200205 4500008004100000022001400041245014200055210006900197260000800266490000700274520126400281653001301545653002901558653002901587653001101616653003501627100001901662700002001681856013901701 2024 eng d a0947-653900aNickel-catalyzed chemodivergent coupling of alcohols: efficient routes to access α,α-disubstituted ketones and α-substituted chalcones0 aNickelcatalyzed chemodivergent coupling of alcohols efficient ro cMAR0 v303 a

Chemodivergent (de)hydrogenative coupling of primary and secondary alcohols is achieved utilizing an inexpensive nickel catalyst, (6-OH-bpy)NiCl2. This protocol demonstrates the synthesis of branched carbonyl compounds, alpha,alpha-disubstituted ketones, and alpha-substituted chalcones via borrowing hydrogen strategy and acceptorless dehydrogenative coupling, respectively. A wide range of aryl-based secondary alcohols are coupled with various primary alcohols in this tandem dehydrogenation/hydrogenation reaction. The nickel catalyst, along with KOtBu or K2CO3, governed the selectivity for the formation of branched saturated ketones or chalcones. A preliminary mechanistic investigation confirms the reversible dehydrogenation of alcohols to carbonyls via metal-ligand cooperation (MLC) and the involvement of radical intermediates during the reaction. The chemodivergent nickel-catalyzed approach provides alpha,alpha-disubstituted ketones from aryl-substituted secondary alcohols and benzyl alcohols via the borrowing hydrogen (BH) strategy in the presence of KOtBu, whereas exclusively alpha-substituted chalcones were accomplished in the presence of mild base K2CO3 through an acceptorless dehydrogenative coupling (ADC) strategy. image

10aAlcohols10adehydrogenative coupling10aMetal-ligand cooperation10aNickel10asubstituted carbonyl compounds1 aBansal, Sadhna1 aPunji, Benudhar uhttp://library.ncl.res.in/content/nickel-catalyzed-chemodivergent-coupling-alcohols-efficient-routes-access-%CE%B1%CE%B1-disubstituted