Organocatalytic Asymmetric Dearomative Oxyalkylation of Indoles Enables Access to C2-Quaternary Indolin-3-ones

Abstract

A facile and efficient asymmetric dearomative oxyalkylation of indoles with TEMPO oxoammonium salt and a variety of aldehydes and ketones has been described. This metal-free approach provides a straightforward access to C2 quaternary oxindoles in high yields with excellent diastereoand enantioselectivities under very mild conditions. The reaction goes smoothly even with only 0.1% equivalent catalyst. Moreover, 2-alkylindoles have proven to be suitable substrates for the first time.

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

“…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]. Encouraged by these results, we envisioned that oxidative dearomatization of indoles with C-H nucleophiles could be achieved under suitable conditions.…”

Progresses in organocatalytic asymmetric dearomatization reactions of indole derivatives

“…In 2019, Zhang and coworkers reported an organo-CADA oxidation of C2-substituted indoles 169 via the reaction with aldehydes or ketones 174 and TEMPO oxoammonium salt in the presence of L-proline C35, which provided oxindole derivatives 175 bearing a C2-quaternary stereogenic center in high yields and excellent stereoselectivities (Scheme 40). 75 Notably, this reaction was not only applicable to C2-aryl indoles 169, but also to C2-alkyl indoles. In the suggested reaction mechanism, C2-substituted indoles 169 reacted with TEMPO oxoammonium to give a complex, which rapidly transformed into oxindol-1-ium intermediates S' through an electron-transfer process.…”

Mechanism‐Based Approach to Reagent Selection for Oxidative Carbon−Hydrogen Bond Cleavage Reactions

“…The low yields with 2 and 3 indicate that rapid alternative pathways exist between vinyl carbamates and these oxidants. Oxoammonium ions act as electrophiles in reactions with electron-rich π-nucleophiles, [18] highlighting a potential limitation of these oxidants in these processes.…”