Iron-Catalyzed C(sp²)–H Alkylation of Indolines and Benzo[h]quinoline with Unactivated Alkyl Chlorides through Chelation Assistance

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(sp²)–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.