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.

本研究首次开发了一种温和且操作简便的吲哚与α-酮酰胺(α-keto amides)的傅-克(Friedel–Crafts)羟基烷基化反应，该反应以水为溶剂，以催化量的磷酸钾(K3PO4)和四丁基溴化铵(nBu4NBr)为催化剂，通过固液界面(solid–liquid interface)的形成进行。该无过渡金属(transition-metal-free)合成策略无需柱层析(column chromatography)纯化，即可得到高纯度的吲哚稠合α-羟基酰胺(α-hydroxy amides)，产物收率从中等到优异不等。该催化体系可循环使用至多5个周期，且可扩展至克级规模反应，这是该转化反应的关键优势。通过氢核磁共振(1H NMR)实验开展的机理研究表明，该反应通过离子交换路径进行。