Deconstructive Oxygenation of Cyclic Amines by Copper-Catalyzed C(sp3)–C(sp3) Bond Cleavage

Herein, we report a copper-catalyzed deconstructive oxygenation platform for the direct conversion of unstrained N-unsubstituted cyclic amines into versatile β-, γ-, and δ-aminoketones. The product diversity is achieved by adjusting the substituents at the β- or γ-position of cyclic amines that proceed through single or consecutive C(sp3)–C(sp3) bond cleavage, respectively. Following this method, we achieved skeletal modification of unstrained cyclic amines through ring contraction or atom replacement, leading to rapid structural diversification of cyclic amines. The synthetic utility of this method was further demonstrated by the efficient synthesis of pharmaceutically relevant molecules, fluoxetine, atomoxetine, and norfluoxetine. Control experiments indicated that, in the presence of the co-oxidant nitroxyl, the copper-catalyzed sequential dehydrogenative oxidation followed by single-electron transfer-induced aerobic oxygenative C–C bond cleavage was responsible for this effective transformation.