Insights into the Mechanism of Metal-Catalyzed Transformation of Oxime Esters: Metal-Bound Radical Pathway vs Free Radical Pathway

Controlling of radical reactivity by binding a radical to the metal center is an elegant strategy to overcome the challenge that radical intermediates are "too reactive to be selective". Yet, its application has seemingly been limited to a few strained-ring substrates, azide compounds, and diazo compounds. Meanwhile, first-row transition-metal-catalyzed (mainly, Fe, Ni, Cu) transformations of oxime esters have been reported recently in which the activation processes are assumed to follow free-radical mechanisms. In this work, we show by means of density functional theory calculations that the activation of oxime esters catalyzed by Fe(II) and Cu(I) catalysts more likely affords a metal-bound iminyl radical, rather than the presumed free iminyl radical, and the whole process follows a metal-bound radical mechanism. The as-formed metal-bound radical intermediates are an Fe(III)-iminyl radical (S_total = 2, S_Fe = 5/2, and S_iminyl = -1/2) and a Cu(II)-iminyl radical (S_total = 0, S_Cu = 1/2, and S_iminyl = -1/2). The discovery of such novel substrates affording metal-bound radical intermediates may facilitate the experimental design of metal-catalyzed asymmetric synthesis using oxime esters to achieve the desired enantioselectivity.