Oxidative Aminotrifluoromethylation of 1,4-Naphthoquinone

J Org Chem. 2024 Sep 20;89(18):13117-13127. doi: 10.1021/acs.joc.4c01232. Epub 2024 Sep 3.

Abstract

A strategy for convenient and precise oxidative aminotrifluoromethylation of 1,4-naphthoquinone with the Togni reagent and amines has been demonstrated via a radical process. This method allows efficient access for the preparation of a wide range of CF3-functionalized 1,4-naphthoquinones under mild conditions, and its application in late-stage modification of drug molecules is achieved. Mechanistic studies indicate that 1,4-naphthoquinone serves as both a substrate and a catalyst and that the Togni reagent plays a dual role of a substrate and an oxidant. As a result, the title reaction can take place in the dark without external catalysts and oxidants.