1,2‐Dichloroethane‐Assisted Defluorinative Ring‐Opening Reaction of DABCO and Polyfluoroalkyl Peroxides: Synthesis of Fluorinated N‐Ethyl Piperazines

Comprehensive Summary A catalyst‐free and additive‐free ring‐opening reaction of polyfluoroalkyl peroxides, triethylenediamine (DABCO), and 1,2‐dichloroethane (DCE) has been developed for the defluorinative synthesis of structurally diverse piperazines featuring a fluoroenone framework and a N ‐chloroethyl‐substituent with high Z ‐stereoselectivity. The success of this three‐component reaction is attributed to the in situ generation of an active 1‐(2‐chloroethyl)‐1,4‐diazabicyclo[2.2.2]octan‐1‐ium (DABCO·DCE) salt, which judiciously acts as a formal N ‐(2‐chloroethyl)piperazine equivalent in the defluorinative coupling with less‐studied aliphatic fluorinated substances. Impressively, this reaction accomplishes multi‐activation of robust C(sp 3 )‐F, C(sp 3 )‐Cl, C(sp 3 )‐O, and C(sp 3 )‐N bonds in a one‐pot process, offering a practical platform for the late‐stage functionalization of complex molecules. Furthermore, the resulting products can not only serve as versatile building blocks for the synthesis of fluorinated heterocycles, but also undergo C—Cl bond displacement transformations with N ‐, O ‐, and S ‐nucleophiles.