Selective Synthesis of Benzothiophene-Fused Polycyclic, Eight-Membered N-Heterocycles via Amine-Mediated Three-Component Domino Strategy

A product-selective strategy was used to synthesize benzothiophene-fused polycyclic, eight-membered N-heterocycles via a three-component domino reaction of thioisatins under catalyst-free conditions. The reaction between tryptamine, thioisatin, and bromoacetophenone produced benzothiophene-fused polycyclic compounds. In contrast, using D-tryptophan methyl ester hydrochloride instead of tryptamine afforded benzothiophene-fused eight-membered N-heterocycles. DFT calculations showed that the benzothiophene-fused polycyclic compounds formed via the Pictet-Spengler reaction. However, the ester group in D-tryptophan methyl ester hydrochloride changed the reaction pathway and produced benzothiophene-fused eight-membered N-heterocycles.

Automated summary

A product-selective strategy was employed to synthesize benzothiophene-fused polycyclic compounds via a three-component domino reaction. Different substrates led to the formation of different products, impacting the reaction pathway and product structure.