Synthesis of spiroindolenines by intramolecular ipso-iodocyclization of indol ynones

Abstract

A high-yielding fast spirocyclization of easily available indol ynones has been developed by applying N-iodosuccinimide. The formation of the desired product occurs in an atom-economical way, under mild conditions, instantly after the addition of the reagent. The expected 1,2-rearrangement was not observed. The procedure represents a metal free spirocyclization of indoles with an opportunity for further functionalizations.

Visible‐Light‐Promoted Selenylative Spirocyclization of Indolyl‐ynones toward the Formation of 3‐Selenospiroindolenine Anticancer Agents

“…In 2018, Van der Eycken's group reported an intramolecular ipso-iodocyclization of indol ynones with NIS to 3iodospiroindolenines. [8] In 2019, Unsworth's group developed a Pd-catalysted dearomatizing spirocyclization/cross-coupling cascade for the conversion of indole ynones into functionalized spirocycles containing tetrasubstituted alkenes. [9] If the selenyl groups and spiroindolenines core can be simultaneously introduced into organic compounds, a series of new seleniumcontaining spiroindolenines were formed and which provided an opportunity to obtain the pharmaceutical lead compounds or drugs to adjust their bioactivity.…”

“…The single crystals of 3 a was obtained by gradual crystallization in methanol, and character- [16] Then, the investigation of various bases such as Na 2 CO 3 , NaHCO 3 , K 2 CO 3 , Cs 2 CO 3 , NaOAc and KOAc revealed that NaOAc was the optimal base for this reaction and afforded 3 a in 80% yield (Table 1, entries 6 vs 2-7). In addition, a solvent screening study indicated that THF was the most suitable solvent for the formation of 3 a (Table 1, entries 6 vs [8][9][10][11][12]. Moreover, when the reaction was conducted in sunshine, the product 3 a was obtained in 86% yield (Table 1, entry 13).…”

Tandem Reactions of Ynones: via Conjugate Addition of Nitrogen‐, Carbon‐, Oxygen‐, Boron‐, Silicon‐, Phosphorus‐, and Sulfur‐Containing Nucleophiles

“…Indoles are important structures in biologically active molecules and have attracted great attention due to their electronic characteristics –. When the indole moiety is attached to a carbonyl group, spiro indolines– or carbazoles could be formed (Scheme ).…”

“…The Unsworth group and the Van der Eycken group have respectively reported the syntheses of spirocyclic scaffolds. Using Ag(I) salts as catalyst and chiral phosphoric acids (CPAs) as ligand, an asymmetric variant furnished spirocyclic indolenines in up to 89:11 er [Eq.…”

“…Moreover, this kind of cyclization could also be achieved with the aid of NIS [Eq. (55‐2)], I 2 , ICl, or TFA [Eq. (55‐3)] .…”