Aerobic Aliphatic Hydroxylation Reactions by Copper Complexes: A Simple Clip-and-Cleave Concept

A simple imine clip-and-cleave concept has been developed for the selective hydroxylation of non-activated CH bonds in aliphatic aldehydes with dioxygen through a copper complex. The synthetic protocol involves reaction of a substrate aldehyde with N,N-diethyl-ethylendiamine to give the corresponding imine, which is used as a bidentate donor ligand forming a copper(I) complex with [Cu(CH₃ CN)₄ ][CF₃ SO₃ ]. After exposure of the reaction mixture to dioxygen acidic cleavage and aqueous workup liberates the corresponding β-hydroxylated aldehyde. The concept for the hydroxylation of trimethylacetaldehyde as well as adamantane and diamantane 1-carbaldehydes was investigated and the corresponding β-hydroxy aldehydes were obtained with high selectivities. The results of low temperature stopped-flow measurements indicate the formation of a bis(μ-oxido)dicopper complex as reactive intermediate. According to density functional theory (DFT, RI-BLYP-D3/def2-TZVP(SDD)/ COSMO(CH₂ Cl₂ )//RI-PBE-D3/def2-TZVP(SDD)) computations CH bonds suitably predisposed to the [Cu₂ O₂ ]²⁺ core undergo hydroxylation in a concerted step with particularly low activation barriers, which explains the experimentally observed regioselectivities.