Ball‐Milling Assisted Iron‐Catalyzed Difluoromethylation Toward the Synthesis of Valuable Oxindoles

SEM analyses revealed that the ball‐milling and piezoelectric‐mediated radical difluoromethylation might be, in fact, catalyzed by iron contamination of BaTiO 3 due to abrasion of the stainless steel milling assembly (jar and balls). A ball‐milling mediated, Fe‐catalyzed radical difluoromethylation is subsequently developed for the synthesis of valuable difluoromethylated oxindoles. Under a mechanochemical compression, the use of readily accessible PhI(OCOCF 2 H) 2 in the presence of 25 mol% of Fe(OAc) 2 enabled the unprecedented solid‐state formation of the CF 2 H radical, prone to add onto an acrylamide substrate to initiate a radical cascade process affording the desired difluormethylated oxindoles. The practical protocol demonstrates broad substrate scope and functional group tolerance, including N ‐substitution and substitution on the CC double bond or the aromatic ring of the acrylamide substrates. Furthermore, the protocol is extended to the introduction of CF 2 Me, CF 2 Bn, and CF 2 Ph motifs, delivering the corresponding products in moderate to good yields. Radical trapping experiments supported a radical‐based mechanism, while control experiments confirmed the essential role of both the Fe‐catalyst and mechanochemical compression.