Enhancement of CuBr-based catalysts for aerobic alcohol oxidation enabled by rational design of bifunctional ligands featuring both a N-alkyl substituted ethylenediamine skeleton and a TEMPO moiety

The development of a simple and highly efficient catalytic system for the selective oxidation of alcohols in open air is an extremely important but challenging task in the fields of organic chemistry and catalysis. In this study, three novel bifunctional ligands, named L₁-L₃, were designed by combining a N-alkyl substituted ethylenediamine skeleton with a TEMPO moiety varying the length of the linker between the two components. When paired with CuBr, ligand L₂, which contains six methylene groups in the linker, demonstrated excellent catalytic activity in the aerobic oxidation of benzyl alcohol, achieving a quantitative yield under ambient conditions. Moreover, the developed CuBr/L₂ catalytic system exhibited a broad substrate scope, including primary benzylic, heterocyclic, allylic, aliphatic alcohols, and secondary benzylic alcohols. Mechanistic insights were gained using cyclic voltammetry (CV), ultraviolet–visible (UV–vis) spectroscopy, and electron spray ionization mass (ESI-MS) spectrometry, enabling stepwise monitoring of the reaction. These studies revealed that the mono-copper species is a key intermediate, with its oxidation state cycling between Cu(I) and Cu(II), playing a pivotal role in the aerobic oxidation of alcohols. Additionally, the moderate linker length in ligand L₂ facilitated internal interaction between the TEMPO moiety and the copper center, thereby enhancing catalytic activity with a high turnover frequency (TOF) of 33 h⁻¹.