Pd(II)‐Catalyzed Transient Directing Group‐Assisted Regioselective Diverse C4–H Fluoroalkoxylation of Indoles

We reported a palladium(II)‐catalyzed, transient directing group (TDG)–enabled protocol for the regioselective C4H fluoroalkoxylation of indoles. Utilizing an L‐valine–derived TDG, this method allows efficient and site‑selective installation of diverse fluoroalkoxy motifs (e.g., –OCH 2 CF 3 , –OCHF 2 , –OCF 2 CF 2 H) −at the electronically and sterically challenging C4 position under mild conditions. The transformation features a broad substrate scope, excellent tolerance of functional groups, and facile scale‐up. Mechanistic investigations—including competition studies and H/D‐exchange experiments—support a Pd(II)/Pd(IV) catalytic cycle in which, reversible TDG coordination directs C─H activation at C4.