Oxidative Dearomatization of Indoles via Pd-Catalyzed C–H Oxygenation: An Entry to C2-Quaternary Indolin-3-ones

Abstract

An oxidative dearomatization chemistry of 2-arylindole via a unique pathway involving Pd-catalyzed C-H peroxygenation is documented. Coupled with cascade transformation, it provides a new route to access indolin-3-ones bearing a C2-quaternary functionality, including a chiral center (indoxyls), a motif prevalent in indole alkaloids but synthetically underexplored. The method is chemo- and regioselective and compatible with versatile substrates. A mechanism has been outlined on the basis of results of control experiments, isolation/use of intermediates, and spectroscopic studies.

Oxidative Dearomative Cross-Dehydrogenative Coupling of Indoles with Diverse C-H Nucleophiles: Efficient Approach to 2,2-Disubstituted Indolin-3-ones

“…Notably, decreasing the amount of Cu(OTf)2 to 0.005 equivalent had no effect on the reactivity of the reaction (Table 1, entry 10). Moreover, under the optimized conditions, the dimer 6a was obtained in 98% reactions focus on the construction of di-or trimerization of indoles [50,[77][78][79][80], and the reactions of indoles with dissimilar C-H nucleophiles are considerably rare [81][82][83]. Recently, we reported an efficient oxidative dearomatization reaction of indoles [84,85].…”

TBHP Mediated Substrate Controlled Oxidative Dearomatization of Indoles to C2/C3‐Quaternary Indolinones

“…Also, a careful review of literature revealed that TEMPO in the presence of AgNO 3 /Brønsted acid in pyridine solvent gave C3‐quaternary indolinone derivative 3 as a minor product . In a similar manner, organic peroxide mediated C2–H oxygenation of indoles in presence of PdCl 2 and MnO 2 was reported earlier . However, in both cases, free (NH)‐indole was used as a substrate.…”

“…Guchhait et al, reported expensive PdCl 2 /TBHP/MnO 2 reagent system to convert free (NH)–indoles to the corresponding C2‐quaternary indolinone derivatives. Liu and co‐workers reported the TEMPO [(2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl] mediated synthesis of C2‐quaternary indolinones from free (NH)‐indoles .…”

Oxidative Coupling of 3‐Oxindoles with Indoles and Arenes

“…However, this method was limited to electron‐poor coupling partners, and yields with pyrrole were also quite low. Another oxidative transformation was reported by Guchhait et al., utilizing the dearomatization and oxidation of one indole partner to accomplish the coupling with the nucleophile (Scheme B) . Although the functional group compatibility of this method is good, it requires an expensive palladium catalyst and multiple equivalents of oxidant.…”

“…[4] However,t his method was limited to electronpoor coupling partners, and yields with pyrrole were also quite low.A nother oxidative transformation was reported by Guchhaite tal.,u tilizing the dearomatization and oxidation of one indole partnert oa ccomplish the couplingw ith the nucleophile (Scheme 1B). [5] Although the functional group compatibility of this method is good, it requires an expensive palladium catalyst and multiple equivalents of oxidant. As imilar reaction wasr eported by Zhou et al by using ruthenium for the oxidative coupling of indoles, during which one molecule of indole is oxidized to form the oxindole, and am olecule of the indole acts as the nucleophile to form the CÀCb ond (Scheme 1C).…”