Lewis Acid and Fluoroalcohol Mediated Nucleophilic Addition to the C2 Position of Indoles

Abstract

Indole readily undergoes nucleophilic substitution at the C3 site, and many indole derivatives have been functionalized using this property. Indole also forms indolium, which allows electrophilic addition in acidic conditions, but current examples have been limited to intramolecular reactions. C2 site-selective nucleophilic addition to indole derivatives using fluoroalcohol and a Lewis acid was developed.

Synthesis of indolo[2,1‐a]isoquinolines by CF3COOH‐induced cyclization

“…It should be noted that the conversion of 10 to 11 has been carried out in a BF 3 •Et 2 O/(CF 3 ) 2 CHOH system developed by Nishina. [ 68 ]…”

“…The results will be added in a limited number of successful or very promising methods for the alkaloid syntheses in route B. [ 65–68 ]…”

Synthesis of Phaitanthrin E and Tryptanthrin through Amination/Cyclization Cascade

“…However, the transformation remains challenging and the precedents is rare. In addition, the electrophilic C(2) selective reactions of indole have been limited to intramolecular reaction because of the high nucleophilicity at C(3) position of indole, which undergo C(2)/C(3) dimerization . In 2004, Herranz reported the the synthesis of tetracyclic heterocycle initiated by nitrile protonation of tryptophan‐derived α ‐amino nitrile, which cascade sequence proceeded through intramolecular C(2) selective amination of indole ring, followed by intramolecular cyclization at nitrogen atom of indole ring .…”

2H‐[1,3]Oxazino[3,2‐α]indolin‐4(3H)‐ones: A Class Of Polyheterocyclic Indole‐Based Compounds

“…In summary, we presented a facile synthesis of novel indoline‐based polycyclic structures, which are easily obtained by acid‐catalysed intramolecular nucleophilic addition of hydroxyl groups to the 2 position of different indoles . Hereby, the deprotection/cyclization procedure utilizing BBr 3 as deprotection as well as cyclization reagent represents a two‐step cascade reaction .…”