| Increased attention is being focused on the introduction of fluorine atoms or fluorine-containing groups into indoles because the fluorinated indole moiety is common in bioactive products and occupies a privileged position in drug discovery. In recent years, significant progress has been made in the synthesis of fluorinated indoles. However, some of these methods still suffer from limitations, such as, harsh reaction conditions, expensive fluorine reagents, toxic and noble metals, and poor selectivity. Therefore, the development of simple, efficient methods for the preparation of fluorinated indoles is highly desirable.Alternatively, Friedel-Crafts acylation using carboxylic acids as the acylating reagents is an attractive synthesis strategy due to the environmental and economical concerns. Because water is the only byproduct derived from carboxylic acid after the acylation and the carboxylic acids are more stable, less expensive, and easier to handle than anhydrides and acid chlorides. Therefore, the research and development of Friedel-Crafts acylation with carboxylic acids as the acylating reagents has been gained favour of chemists.3-Fluoroacetylindoles have good biological activities and are also important intermediates of the pharmaceuticals. Despite the great number of methods for the preparation of trifluoromethylindoles already available, the synthesis of fluoroacetylindoles has rarely been developed. Therefore, the development of the new approaches for synthesis of the diveres 3-fluoroacetylindoles is very significant and valuable. In this paper, we firstly reviewed the synthesis methods for the preparation of fluorinated indoles and the development of Friedel-Crafts acylation with carboxylic acids as the acylating reagents in recent years. Then, we researched Friedel-Crafts fluoroacetylation of indoles using commercially available trifluoroacetic acid, chlorodifluoroacetic acid, bromodifluoroacetic acid, and difluoroacetic acid as the fluoroacetylating reagents. The new approach displays a powerful method for the construction of diverse 3-fluoroacetylindoles. |
