The application of acyl radical chemistry in organic synthesis is a well-known approach. On the other hand, the related carbamoyl species are scarcely exploited. Recently, we became very interested in carbamoyl radicals since, we envisioned that functionalized heterocycles could be prepared from formamides and N-arylacrylamides as starting materials. Our first target was pyrroloindoline skeleton, which can be found frequently in many alkaloids displaying remarkable biological properties.<br/>For this purpose, a process based on functionalized 3,3-disubstituted oxindoles as key intermediates for the direct synthesis of pyrroloindolines was designed. The protocol for the synthesis of 3,3-disubstituted oxindoles was developed by using a Fenton-type reaction, with hydrogen peroxide and iron(II), under acidic medium, to produce hydroxyl radical and then generate the carbamoyl radical. This methodology was applied for a wide range of N-alkyl-N-arylacrylamides, and we were able to produce functionalized 3,3-disubstituted oxindoles in excellent yields.<br/>Aiming to increase the productivity of oxindoles, we decided to use a Photo-Fenton reaction, under continuous flow conditions, to generate the carbamoyl radicals. Fortunately, a faster and improved protocol to produce oxindoles was developed, only with 10 min reaction.<br/>Considering the success of our methodology, we are now aiming Late-Stage Functionalization of 3,3-disubstituted oxindoles as a very attractive tool for the diversity oriented synthesis of spirooxindoles, which also will be presented in this talk.

Exploitation of carbamoyl radicals to create a shortcut for the synthesis of pyrroloindolines and spirooxindoles

2019 Spring National Meeting

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