Weak Chelation-Assisted C4-Selective Alkylation of Indoles with Cyclopropanols via Sequential C–H/C–C Bond Activation

Abstract

A Rh-catalyzed weak chelation-guided C4-alkylation of indoles has been accomplished using cyclopropanols as an alkylating agent via the cascade C–H and C–C bond activation. The substrate scope, functional group tolerance, and late-stage mutation of drug molecules are the important practical features.

Transition-Metal-Catalyzed Directed C8–H Carbon–Carbon Bond Formation in Quinolines and 1,2,3,4-Tetrahydroquinolines

“…In 2022, the Koley group reported the C8-selective 2-aminoethylation of a THQ utilizing a N -Ts-aziridine in the presence of a Pd catalyst (Scheme 9 C), 34 while our group achieved the C8-alkylation of THQ with cyclopropanol using Rh-catalyzed sequential C–H and C–C bond activation (Scheme 9 D). 35…”

Strained cycloalkanols in C–C bond formation reactions: a boon in disguise!

“…On similar lines, a weak, chelation-assisted C(4)-alkylation of 3-acetyl-N-protected indoles was reported by Punniyamurthy and co-workers under a [Cp*RhCl 2 ] 2 catalyzed condition. 85 The formation of Rh-homoenolates and their subsequent transformation to enones characterize the mechanistic pathway (Scheme 44c). A Rh(III)-catalyzed C(2)-alkylation of N,N-dialkylcarbamoyl indoles was reported by Anbarasan and co-workers, by the ring scission of cyclopropanols.…”

Arylation of Cyclopropanol with Pyrrole: Asymmetric Synthesis of Indolizidine 167B, Indolizidine 209D, and Monomorine I

“…Early efforts were focused on metal-catalyzed cross-coupling of cyclopropanols with (hetero)­aryl halides . Recently, metal-catalyzed ring-opening couplings of cyclopropanols with (hetero)­arenes bearing adjacent chelating groups via C–H activation have been developed . Direct arylations of cyclopropanols through a process of radical ring-opening addition and then aromatization have been established as a straightforward and atom-economic alternative .…”