Indoles and N-alkylindoles undergo Friedel–Crafts addition to aldehydes in the presence of trimethylsilyl trifluoromethanesulfonate and a trialkylamine to produce 3-(1- silyloxyalkyl)indoles. Neutralization of the reaction mixture with pyridine followed by deprotection under basic conditions with tetrabutylammonium fluoride provides the 1:1 adduct as the free alcohol. This method prevents spontaneous conversion of the desired products to the thermodynamically favored bisindolyl(aryl)methanes, a process typically observed when indoles are reacted with aldehydes under acidic conditions.
Copyright © 2015, Journal of Organic Chemistry.
C. Wade Downey, Christopher D. Poff,* Alissa N. Nizinski.* Friedel−Crafts Hydroxyalkylation of Indoles Mediatedby Trimethylsilyl Trifluoromethanesulfonate. Journal of Organic Chemistry 2015, 80, 10364-10369.