Friedel–Crafts Addition of 3‑Alkylated Indoles to Aldehydes: 2‑Hydroxyalkylation Promoted by Trimethylsilyl Trifluoromethanesulfonate

In the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and 2,6-lutidine, 3-alkylated indoles undergo Friedel–Crafts silyloxyalkylation when treated with nonenolizable aldehydes. The reaction is general across a wide range of aromatic aldehydes and tolerates a variety of N-alkylated indoles. Deprotection of the silylated product occurs under standard conditions, and in certain cases the initial TMS-protected product can be isolated in high yield.