Regioselective C3-Fluoroalcoholation of Indoles with Heptafluoroisopropyl Iodide via Palladium-Catalyzed C(sp)-C(sp) Cross-Coupling in the Presence of O.

An efficient method for C3-fluoroalcoholation of indole derivatives was developed by merging C-F cleavage and C-C bond coupling, using free (NH)-indoles and heptafluoroisopropyl iodides as precursors. Preliminary mechanistic studies indicate that the bimetallic co-mediated C-F bond cleavage and the trifluoroacetate moiety play an essential role. Notably, this strategy constructs derivatizations through the modifiable carbon-oxygen bond. A broad range of structurally valuable organofluorine products was obtained, which shows excellent functional group tolerance. Furthermore, easily accessible materials were utilized and circumvented two troublesome steps of installing and removing an external auxiliary. This is the first report to introduce 3-fluoroalcoholated indoles via fluorohalides. This reaction offers a straightforward and efficient platform to access worthwhile fluorinated free (NH)-heteroarenes derivatives.