Metal-free, Phosphoric Acid-catalyzed Regioselective 1,6-Hydroarylation of para-Quinone Methides with Indoles in Water

An efficient, cheap and green protocol for the highly regioselective 1,6-hydroarylation of para-quinone methides (p-QMs) with indoles at the C-3 position has been established by phosphoric acid catalysis in water under transition-metal-free reaction conditions. A wide range of indole derivatives and para-quinone methides (p-QMs) are compatible for the reaction, affording the corresponding 1,6-hydroarylation products with good to excellent yields. The possible mechanism of the reaction has been explored through step-by-step control experiments. The protocol is convenient for practical applications, leading to a safe, green and feasible way for the formation of C-3 diarylmethyl functionalized indole derivatives.

Automated summary

An efficient, cheap and green protocol has been established for the highly regioselective 1,6-hydroarylation of para-quinone methides (p-QMs) with indoles at the C-3 position using phosphoric acid catalysis in water under transition-metal-free reaction conditions. A wide range of indole derivatives and p-QMs are compatible, providing good to excellent yields of the corresponding 1,6-hydroarylation products. The possible mechanism of the reaction has been explored through step-by-step control experiments, making this protocol a convenient, safe, green and feasible way for the formation of C-3 diarylmethyl functionalized indole derivatives.