Lewis‐Acid‐Catalysed Reaction of 3‐Hydroxy‐2‐oxindoles with Terminal Alkynes: Synthetic Approaches to the Pyrroloindoline Alkaloids

Abstract

Lewis‐acid‐catalysed reaction of 3‐hydroxy‐2‐oxindoles with a variety of terminal alkynes has been developed. The key step involves alkylation of 3‐aryl (or) 3‐alkyl, 3‐hydroxyoxindoles with terminal alkyne as π‐electron‐rich system to give a variety of 2‐oxindoles with an all‐carbon quaternary centre. On further extension of this method, a variety of spiro‐2‐oxindoles have been synthesized in high yields. The aforementioned methodology has been used in addressing the cyclotryptamine alkaloids linked with aryl group at the pseudobenzylic position.

FeCl3-Catalyzed Allylation Reactions onto 3-Hydroxy-2-oxindoles: Formal Total Syntheses of Bis-cyclotryptamine Alkaloids, (±)-Chimonanthine, and (±)-Folicanthine

“…One of the most powerful methods for construction of all-carbon quaternary centers is the Lewis acid activation of 3-hydroxy-2-oxindoles followed by reaction with a suitable nucleophile . Toward this end, recently, our group has reported efficient Lewis acid catalyzed activation of 3-alkyl-3-hydroxy-2-oxindole with various electron-rich substrates . These reactions presumably go through in situ generation of reactive intermediate 2 H -indol-2-one of type 8 (Scheme ).…”

“…As described in ref , isatin derivative (18 mmol; 1.0 equiv) was taken in MeOH at 25 °C. To this solution was added indole (21.6 mmol; 1.2 equiv).…”

“…The crude product was washed with Et 2 O to remove excess indole from the desired products 6a and 13 . For the characterization of compound 6a , see ref .…”

Fe‐Catalysed Coupling Reactions Between Alkynes and Alcohols

“…In 2017, the research group of Bisai, developed a Lewis acid (FeCl 3 or Sn(OTf) 2 ) catalysed coupling of 3-hydroxy-2oxindoles 6 with terminal alkynes 2 for the synthesis of key intermediates 7 in the total synthesis of pyrroloindoline alkaloids (Scheme 2). [7] This strategy gives structurally diverse 2-oxindoles 7 with an all-carbon quaternary centre at C-3 Mr. Siddique Khan is from West Bengal, India. He completed his Master of Science (M.Sc.)…”

Six-Membered Ring Systems: With O and/or S Atoms

“…Six-Membered Ring Systems: With O and/or S Atoms terminal arylacetylenes promoted by Lewis acids Sn(OTf) 2 or FeCl 3 ,i n dichloromethane(17EJO3078). A three-component reaction of 6H-pyrrolo[3,2,1-de]acridine-1,2-dione with cyclohexane-1,3-diones/barbituric acid derivatives and malononitrile/ethyl cyanoacetate in the presence of triethylamine in refluxing ethanol leads to spiropyrroloacridone 2-aminotetrahydrochromene derivatives(17JHC2223).…”