Unraveling the divergent mode of Cu- or Zn-assisted radical addition of imines: a mechanistic perspective on Lewis acidic metal-induced enantioselectivity

Abstract

As widely used Lewis acidic metals, Cu and Zn possess distinct redox properties and coordination modes, potentially leading to different radical addition mechanisms. Achieving precise control over the stereoselectivity of imine addition reactions assisted by these differing Lewis acidic metals remains to be a significant challenge. In this report, we present computational evidence that the mode of radical addition is governed by the redox properties of Cu and Zn. In Cu-assisted radical addition, Cu(I) species are prone to oxidation, leading to the formation of a Cu(II)-amino intermediate. Conversely, due to the stable oxidation state of the Zn(II) species, a metal-stabilized amino radical is formed during Zn-assisted radical addition, while the oxidation state of Zn remains unchanged. NCI analysis reveals the origin of the opposite enantioselectivity observed in Cu- or Zn-assisted radical additions. The distinct coordination modes of the Lewis acidic metals give rise to π–π interactions that dictate the direction of radical attack, leading to differences in enantioselectivity. We anticipate that the mode of Lewis acidic metal-assisted radical addition may extend to other imine addition processes and explain the unique effectiveness of Lewis acidic metals in many instances.