A Two-Step Synthesis of Unprotected 3-Aminoindoles via Post Functionalization with Nitrostyrene

A novel, low-cost method for the preparation of not easily accessible free 3-aminoindoles has been developed. This approach is based on a well-established reaction between indoles and nitrostyrene in the presence of phosphorous acid, which results in the formation of 4'-phenyl-4'H-spiro[indole-3,5'-isoxazoles]. The latter could be transformed to corresponding aminated indoles by reaction with hydrazine hydrate in good or excellent yields upon microwave-assisted heating.

Automated summary

A novel and cost-effective method was developed for the synthesis of free 3-aminoindoles which are typically difficult to access. This method involved the reaction between indoles and nitrostyrene in the presence of phosphorous acid, leading to the formation of 4'-phenyl-4'H-spiro[indole-3,5'-isoxazoles]. These isoxazoles could be efficiently transformed into the desired aminated indoles through a reaction with hydrazine hydrate under microwave-assisted heating.