An Umpolung Strategy for the Synthesis of β-Aminoketones via Copper-Catalyzed Electrophilic Amination of Cyclopropanols

A novel copper-catalyzed electrophilic amination of cyclopropanols with O-benzoyl-N,N-dialkylhydroxylamines to synthesize various beta-aminoketones via a sequence that includes C-C bond cleavage and C-sp(3)-N bond formation is reported. The reaction conditions are mild and tolerate a wide range of functional groups including benzoate, tosylate, expoxide, and alpha,beta-unsaturated carbonyls, which are incompatible in the traditional amine nucleophilic conjugate addition and the Mannich reaction conditions. Preliminary mechanistic studies and a proposed catalytic cycle of this umpolung beta-aminoketone synthesis process have been described as well.