@article {46798, title = {Iron-catalyzed C(sp(2))-H alkylation of indolines and benzo[h]quinoline with unactivated alkyl chlorides through chelation assistance}, journal = {ACS Catalysis}, volume = {10}, year = {2020}, month = {JUL }, pages = {7312-7321}, type = {Article}, abstract = {

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.

}, keywords = {alkyl chlorides, Alkylation, C-H activation, chelation assistance, indolines, iron}, issn = {2155-5435}, doi = {10.1021/acscatal.0c02030}, author = {Jagtap, Rahul A. and Samal, Pragnya Paramita and Vinod, C. P. and Krishnamurty, Sailaja and Punji, Benudhar} } @article {47036, title = {Unactivated alkyl halides in transition-metal-catalyzed C-H bond alkylation}, journal = {ACS Catalysis}, volume = {11}, year = {2021}, month = {MAR }, pages = {3268-3292}, type = {Review}, abstract = {

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.

}, keywords = {(hetero)arenes, Alkylation, C-H activation, transition metals, unactivated alkyl halides}, issn = {2155-5435}, doi = {10.1021/acscatal.0c05580}, author = {Ankade, Shidheshwar B. and Shabade, Anand B. and Soni, Vineeta and Punji, Benudhar} } @article {47999, title = {Manganese-catalyzed C(sp(2))-H alkylation of indolines and arenes with unactivated alkyl bromides}, journal = {Chemistry-an Asian Journal}, volume = {17}, year = {2022}, month = {MAY}, pages = {e202200103}, type = {Article}, abstract = {

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.

}, keywords = {Alkylation, C-H activation, indoline, ligand-free, manganese}, issn = {1861-4728}, doi = {10.1002/asia.202200103}, author = {Verma, Suryadev K. and Punji, Benudhar} } @article {49125, title = {Advances in the iron-catalyzed direct functionalizations of heterocycles}, journal = {Synlett}, volume = {34}, year = {2023}, month = {APR}, pages = {683-697}, type = {Article}, abstract = {

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

}, keywords = {Alkylation, azoles, C-H functionalization, heterocycles, indoles, iron, Mechanism}, issn = {0936-5214}, doi = {10.1055/a-1890-8503}, author = {Pradhan, Chandini and Punji, Benudhar} } @article {49298, title = {Nickel-catalyzed branch-selective C-H alkylation of indoles and azoles with alkenes: an additive- and solvent-free approach}, journal = {European Journal of Organic Chemistry}, volume = {27}, year = {2024}, month = {JUL }, type = {Article}, abstract = {

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

}, keywords = {Alkylation, branch selectivity, indoles, Nickel, solvent-free synthesis}, issn = {1434-193X}, doi = {10.1002/ejoc.202400376}, author = {Ankade, Shidheshwar B. and Banerjee, Shuvajit and Punji, Benudhar} }