02123nas 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-chlorides01604nas a2200241 4500008004100000022001400041245008000055210006900135260000900204300001400213490000700227520082200234653001901056653001501075653001901090653002201109653003001131100002801161700002301189700001801212700002001230856011201250 2021 eng d a2155-543500aUnactivated alkyl halides in transition-metal-catalyzed C-H bond alkylation0 aUnactivated alkyl halides in transitionmetalcatalyzed CH bond al cMAR  a3268-32920 v113 a

Alkylation represents an important organic transformation in molecular science to develop privileged alkylated arenes and heteroarenes. Especially, the direct C-H bond alkylation using unactivated alkyl halides is a straightforward and attractive approach from both the step-economy and chemoselectivity perspectives. Substantial progress has been made in the direct alkylation using primary, secondary, and tertiary alkyl halides along with the methylation and fluoroalkylation. This Review broadly summarizes the transition-metal-catalyzed alkylations of C-H bonds on various arenes and heteroarenes with unactivated alkyl halides until October 2020. On the basis of the substrates utilized for alkylation, the Review is divided into two major sections: alkylation of arenes and alkylation of heteroarenes.

10a(hetero)arenes10aAlkylation10aC-H activation10atransition metals10aunactivated alkyl halides1 aAnkade, Shidheshwar, B.1 aShabade, Anand, B.1 aSoni, Vineeta1 aPunji, Benudhar uhttps://library.ncl.res.in/content/unactivated-alkyl-halides-transition-metal-catalyzed-c-h-bond-alkylation01477nas a2200217 4500008004100000022001400041245010200055210006900157260000800226300001500234490000700249520075700256653001501013653001901028653001301047653001601060653001401076100002401090700002001114856012501134 2022 eng d a1861-472800aManganese-catalyzed C(sp(2))-H alkylation of indolines and arenes with unactivated alkyl bromides0 aManganesecatalyzed Csp2H alkylation of indolines and arenes with cMAY ae2022001030 v173 a

Selective C(sp(2))-H bond alkylation of indoline, carbazole and (2-pyridinyl)arenes with unactivated alkyl bromides is achieved using MnBr2 catalyst in the absence of an external ligand. The alkylation uses a simple LiHMDS base and avoids the necessity of Grignard reagent, unlike other Mn-catalyzed C-H functionalization. This reaction proceeded either through a five- or a less-favored six-membered metallacycle, and tolerated diverse functionalities, including alkenyl, alkynyl, silyl, aryl ether, pyrrolyl, indolyl, carbazolyl and alkyl bearing fatty alcohol and polycyclic-steroid moieties. Alkylation follows a single electron transfer (SET) pathway involving 1e oxidative addition of alkyl bromide and a rate-limiting C-H metalation.

10aAlkylation10aC-H activation10aindoline10aligand-free10amanganese1 aVerma, Suryadev, K.1 aPunji, Benudhar uhttps://library.ncl.res.in/content/manganese-catalyzed-csp2-h-alkylation-indolines-and-arenes-unactivated-alkyl-bromides01698nas 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-and