Biomimetic Cu/Nitroxyl Catalyst Systems for Selective Alcohol Oxidation

Abstract

The oxidation of alcohols to the corresponding carbonyl products is an important organic transformation and the products are used in a variety of applications. The development of catalytic methods for selective alcohol oxidation have garnered significant attention in an attempt to find a more sustainable method without any limitations. Copper, in combination with 2,2,6,6-tetramethyl-1-piperidine N-oxyl (TEMPO) and supported by organic ligands, have emerged as the most effective catalysts for selective alcohol oxidation and these catalyst systems are frequently compared to galactose oxidase (GOase). The efficiency of GOase has led to extensive research to mimic the active sites of these enzymes, leading to a variety of Cu/TEMPO· catalyst systems being reported over the years. The mechanistic pathway by which Cu/TEMPO· catalyst systems operate has been investigated by several research groups, which led to partially contradicting mechanistic description. Due to the disadvantages and limitations of employing TEMPO· as co-catalyst, alternative nitroxyl radicals or in situ formed radicals, as co-catalysts, have been successfully evaluated in alcohol oxidation. Herein we discuss the development and mechanistic elucidation of Cu/TEMPO· catalyst systems as biomimetic alcohol oxidation catalysts.

2,2,6,6‐Tetramethylpiperidinyloxyl (TEMPO) Radical Mediated Electro‐Oxidation Reactions: A Review

“…One of the major limitations of TEMPO-mediated electrochemical oxidation is the requirement of high electrode potential to generate reactive oxoammonium species. [108] Also, the high cost of TEMPO as a co-catalyst, lack of recyclability, and its steric influence on reactivity has resulted in attempts to replace TEMPO with a sterically smaller and more economic nitroxyl co-catalyst. In addition, the improvement of the system's capability to oxidize both primary and secondary alcohols is also of great importance.…”

Catalytic Oxidations in a Bio-Based Economy

“…Consequently, alternative methods have been developed that use "earth abundant" metals, such as copper and iron, as catalysts. One method with broad applications in the selective oxidation of primary alcohols to aldehydes, even in the presence of secondary alcohols, involves the combination of a Cu(II)bipyridine (Cu-bpy) complex with a base, such as potassium hydroxide, a stable nitroxyl radical, exemplified by 2,2,6,6tetramethyl-1-piperidine-N-oxyl (TEMPO) and its derivatives, at ambient temperature with air in aqueous acetonitrile (Figure 2; Gamez et al, 2003;Sheldon and Arends, 2004;Marais and Swarts, 2019). The generally accepted mechanism involves as the key, rate determining step, abstraction of a hydrogen atom from an alkoxide ligand by a coordinated nitroxyl radical analogous to that involved in the aerobic oxidation of primary alcohols catalyzed by the copper-dependent oxidase, galactose oxidase (Dijksman et al, 2003).…”

Recent Advances in Copper Catalyzed Alcohol Oxidation in Homogeneous Medium

“…DFT calculations suggested a mixed valence Cu II /Cu I complex intermediate, (Figure 9) in which the spin electron density is mostly concentrated at one of the Cu atoms and at the DAPTA = O ligand. The knowledge that external bases have an effect on the catalytic activity, as well as on the selectivity and stability of the catalytic systems, has led to the development of new ones able to operate in the absence of an added base [29]. Theoretical and experimental studies revealed that appropriate ligands enhance the electron density of the Cu center (e.g., by ligand-to-metal charge transfer (LMCT)), leading to a complex with a suitable alkalinity and suggesting that a basic anion in the Cu-complex could be more efficient for promoting the oxidation reaction than an external base added.…”