Recent Advances in Metal‐catalyzed Alkylation, Alkenylation and Alkynylation of Indole/indoline Benzenoid Nucleus

Abstract

Selective editing of the benzenoid CÀ H bonds (C4À C7) in indoles/indolines has received great interest because functionalized indoles/indolines are featured in many marketed drugs and natural products. Transition-metalcatalyzed directed CÀ H functionalization has thus been developed to manipulate the benzenoid core through CÀ C and C-heteroatom bond formation. This review covers the recent advances in selective CÀ C bond forming reactions, alkylation, alkenylation and alkynylation, over the benzenoid ring (C4À C7) of indoles/indolines using metal catalysis.

Merging C–H Bond Activation, Alkyne Insertion, and Rearrangements by Rh(III)-Catalysis: Oxindole Synthesis from Nitroarenes and Alkynes

“…In the presence of LiAlH 4 , the selective reduction of the acetyl group was observed, affording the indolin-2-one 17 in 97% yield, while compound 1 was fully reduced using borane–tetrahydrofuran to deliver 34 in 80% yield. These 3,3-disubstituted indolineswhich are architectures embedded in many complex alkaloids or key building blocksare now easy to prepare from nitrobenzene in only two steps, where formerly multistep synthesis was necessary . Due to the strongly electron-withdrawing nature of the nitro group, the main limitation of our novel cascade reaction is incompatibility with electron-poor nitroarenes because of an unfavorable C–H bond activation .…”

Cp*CoIII-Catalyzed C(7)–H Bond Annulation of Indolines with Alkynes

“…On the basis of the preliminary experiments and previous literature, ,, a plausible mechanism is proposed in Scheme . The reaction mechanism is initiated by the formation of the in situ generated cationic [Co] complex A .…”

“…Inspired by the unique nucleophilic activity of organocobalt species over organorhodium species reported by Matsunaga and Kanai, , we envisaged annulating the C(7)–H bond of indoline with various alkynes. It is expected that the cobalt catalyst may undergo six-membered cyclometalation at the C(7) position , of indoline assisted by a carbamoyl directing group . The alkyne further inserts into the organocobalt species to produce an alkenyl–cobalt intermediate that subsequently facilitates the nucleophilic attack of [Co]–C to the less electrophilic carbamoyl group, leading to the annulation product with the liberation of a secondary amine.…”

Breaking the Trend: Insight into Unforeseen Reactivity of Alkynes in Cobalt-Catalyzed Weak Chelation-Assisted Regioselective C(4)–H Functionalization of 3-Pivaloyl Indole

“…Nevertheless, in recent years, various methods have been developed for benzenoid C–H functionalization at the C6 and C7 positions of indole using N -protected directing groups . However, selective C(4)–H functionalization is an underdeveloped and challenging task, which can be addressed by installing a directing group at the C3 position of indole . Despite the proximal directing group, the inherent challenge that makes the functionalization of indole C(4)–H difficult is the formation of a five-membered metallacycle at the C2 position, as compared to six-membered metallacycle at the C4 position (Figure b).…”