Copper Catalyzed C–H Sulfonylation of Benzylamines with a Catalytic Transient Directing Group

Transient CH functionalization involves the dynamic in situ generation of a directing group to allow directed C–H activation/cyclometallation and subsequent functionalization steps. To date most examples involve precious metal catalysis, commonly using palladium. Here we report the first example of copper catalysed C(sp2)–H functionalization of benzylamines using a transient directing group (TDG), also employed catalytically. A dual catalytic system with copper(II) acetate and 2-hydroxynicotinaldehyde enabled effective sulfonylation of numerous benzylamines via a transiently formed imine directing group. Manganese(IV) oxide was identified as an effective terminal oxidant and base for this transformation, enabling a diverse array of sulfinate salts and benzylamines to be coupled in good yields. Computational DFT investigations suggest a turnover limiting CH activation step with a facile combination of the cupracycle with an RSO2 radical. The TDG is shown promote the reaction by lowering the energy barrier for an acetate mediated concerted metalation deprotonation in comparison to a potential free amine directed process.