Mechanism of Copper(I)/TEMPO-Catalyzed Aerobic Alcohol Oxidation

Abstract

Homogeneous Cu/TEMPO catalyst systems (TEMPO = 2,2,6,6-tetramethylpiperidine-N-oxyl) have emerged as some of the most versatile and practical catalysts for aerobic alcohol oxidation. Recently, we disclosed a (bpy)CuI/TEMPO/NMI catalyst system (NMI = N-methylimidazole) that exhibits fast rates and high selectivities, even with unactivated aliphatic alcohols. Here, we present a mechanistic investigation of this catalyst system, in which we compare the reactivity of benzylic and aliphatic alcohols. This work includes analysis of catalytic rates by gas-uptake and in situ IR kinetic methods and characterization of the catalyst speciation during the reaction by EPR and UV–visible spectroscopic methods. The data support a two-stage catalytic mechanism consisting of (1) “catalyst oxidation” in which CuI and TEMPO–H are oxidized by O2 via a binuclear Cu2O2 intermediate and (2) “substrate oxidation” mediated by CuII and the nitroxyl radical of TEMPO via a CuII-alkoxide intermediate. Catalytic rate laws, kinetic isotope effects, and spectroscopic data show that reactions of benzylic and aliphatic alcohols have different turnover-limiting steps. Catalyst oxidation by O2 is turnover limiting with benzylic alcohols, while numerous steps contribute to the turnover rate in the oxidation of aliphatic alcohols.

Oxidovanadium complexes with tridentate aroylhydrazone as catalyst precursors for solvent-free microwave-assisted oxidation of alcohols

“…Addition of TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) radical, an efficient mediator for the aerobic oxidation of alcohols [23,24,[61][62][63][64][65], although scarcely used for the peroxidative oxidation [35,43,66,67] of those substrates, provided almost quantitative formation of acetophenone (Fig. 3) and a significant increase in cyclohexanone yield (from 38 to 58% (2), Fig.…”

Scalable thin-layer membrane reactor for heterogeneous and homogeneous catalytic gas–liquid reactions

“…[22][23][24] However, the practical usage of aerobic oxidation in large-scale synthesis raises safety concerns, namely the formation of explosive mixtures (flammable organic solvents in oxygen). A number of microreactor-based biphasic flow implementations of aerobic oxidation improve the safety profile by accurately controlling oxygen flow in the microchannels.…”

Gas–Liquid Segmented Flow Microfluidics for Screening Copper/TEMPO‐Catalyzed Aerobic Oxidation of Primary Alcohols

“…[9,10,27] High conversion (70%) of benzyl alcohol was obtained in 5 min at room temperature using 5 bar of oxygen. The conversion as a function of residence time was then studied ( Figure 2).…”

“…Simplified catalytic cycle for the Cu-catalysed aerobic oxidation of primary alcohols (adapted from refs. [10,11] ). (about 2 and 5% absolute and relative conversion, respectively), both possibilities lead to the same dependency between conversion and residence time.…”

“…This behaviour is in accordance with the proposed mechanism where the aerobic oxidation of Cu(I) is rate-controlling (steps A in Scheme 1) in a classical stirred flask. [9,10] The improvement of oxygen mass transfer changes the turnover-limiting step of the catalytic system (Scheme 1) and we can speculate that under Taylor flow conditions, the rate of aerobic oxidation of Cu(I) (steps A) became slightly faster than steps B and C corresponding to the formation of Cu-alkoxide species and oxidation of the alcohol to the aldehyde via hydrogen transfer to TEMPO consistent with the reduction of Cu(II) to Cu(I).…”