Rh-Catalyzed oxidation and trifluoroethoxylation of N-aryl-pyrrolidin-2-ones: a domino approach for the synthesis of N-aryl-5-(2,2,2-trifluoroethoxy)-1,5-dihydro-2H-pyrrol-2-ones?

Organic Chemistry Frontiers Pub Date: 2022-01-26 DOI: 10.1039/D1QO01319J

Abstract

The synthesis of trifluoroethoxylated dihydropyrrolidones via rhodium-catalyzed oxidation and trifluoroethoxylation of pyrrolidones is presented in this paper. This process realized the trifluoroethoxylation of non-activated sp3 C–H by a domino approach for the first time, without requiring the preparation of substrates with halogens or guiding groups. The formed α,β-unsaturated-γ-butyrolactams can be further functionalized via the Michael addition reaction or realize the exchange of the trifluoroethoxy group to the hexafluoroisopropoxy group. Such compounds exhibit anti-tumor activity in vitro and can be used as hit compounds for further research. This method provides an efficient domino approach for generating various trifluoroethoxylated dihydropyrrolidones.

Graphical abstract: Rh-Catalyzed oxidation and trifluoroethoxylation of N-aryl-pyrrolidin-2-ones: a domino approach for the synthesis of N-aryl-5-(2,2,2-trifluoroethoxy)-1,5-dihydro-2H-pyrrol-2-ones
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