Friedel-Crafts Hydroxyalkylation of Indoles with α-Keto Amides using Reusable K3PO4/ nBu4NBr Catalytic System in Water.

A mild and operationally simple Friedel-Crafts hydroxyalkylation of indoles with α-keto amides was developed for the first time by using catalytic amount of K3PO4 and nBu4NBr in water as solvent through a solid-liquid interface formation. The transition-metal-free protocol does not demand column chromatography purification and results in highly pure indole fused α-hydroxy amides in good to excellent yields. Reusability of the catalytic system up to five cycles and extension to a gram-scale reaction are the key advantages of this transformation. The mechanistic study involving 1H NMR experiments reveals that the reaction proceeds via ion exchange pathway.