This Minireview presents recent important homogenous aerobic oxidative reactions which are assisted by electron transfer mediators (ETMs). Compared with direct oxidation by molecular oxygen (O-2), the use of a coupled catalyst system with ETMs leads to a lower overall energy barrier via stepwise electron transfer. This cooperative catalytic process significantly facilitates the transport of electrons from the reduced form of the substrate-selective redox catalyst (SSRCred) to O-2, thereby increasing the efficiency of the aerobic oxidation. In this Minireview, we have summarized the advances accomplished in recent years in transition-metal-catalyzed as well as metal-free aerobic oxidations of organic molecules in the presence of ETMs. In addition, the recent progress of photochemical and electrochemical oxidative functionalization using ETMs and O-2 as the terminal oxidant is also highlighted. Furthermore, the mechanisms of these transformations are showcased.

A well-studied heterogeneous palladium(II) catalyst used for the cycloisomerization of acetylenic acids is known to be susceptible to deactivation through reduction. To gain a deeper understanding of this deactivation process and to enable the design of a reactivation strategy, in situ X-ray absorption spectroscopy (XAS) was used. With this technique, changes in the palladium oxidation state and coordination environment could be studied in close detail, which provided experimental evidence that the deactivation was primarily caused by triethylamine-promoted reduction of palladium(II) to metallic palladium nanoparticles. Furthermore, it was observed that the choice of the acetylenic acid substrate influenced the distribution between palladium(II) and palladium(0) species in the heterogeneous catalyst after the reaction. From the mechanistic insight gained through XAS, an improved catalytic protocol was developed that did not suffer from deactivation and allowed for more efficient recycling of the catalyst.

Herein we report the first Fe-II-catalyzed aerobic biomimetic oxidation of amines. This oxidation reaction involves several electron transfer steps and is inspired by biological oxidation in the respiratory chain. The electron transfer from the amine to molecular oxygen is aided by two coupled catalytic redox systems, which lower the energy barrier and improve the selectivity of the oxidation reaction. An iron hydrogen transfer complex was utilized as the substrate-selective dehydrogenation catalyst along with a bifunctional hydroquinone/cobalt Schiff base complex as a hybrid electron transfer mediator. Various primary and secondary amines were oxidized in air to their corresponding aldimines or ketimines in good to excellent yield.

The activation process of a known Ru-catalyst, dicarbonyl(pentaphenylcyclopentadienyl)ruthenium chloride, has been studied in detail using time resolved in situ X-ray absorption spectroscopy. The data provide bond lengths of the species involved in the process as well as information about bond formation and bond breaking. On addition of potassium tert-butoxide, the catalyst is activated and an alkoxide complex is formed. The catalyst activation proceeds via a key acyl intermediate, which gives rise to a complete structural change in the coordination environment around the Ru atom. The rate of activation for the different catalysts was found to be highly dependent on the electronic properties of the cyclopentadienyl ligand. During catalytic racemization of 1-phenylethanol a fast-dynamic equilibrium was observed.

The focus of this thesis is twofold: The first is on the application of iron catalysis for organic transformations. The second is on the use of in situ X-ray absorption spectroscopy (XAS) to investigate the mechanisms of a heterogeneous palladium-catalyzed reaction and a homogeneous ruthenium-catalyzed reaction.

In chapters two, three and four, the use of iron catalyst VI, or its analog X, is described for (I) the DKR of sec-alcohols to produce enantiomerically pure acetates; (II) the cycloisomerization of α-allenols and α-allenic sulfonamides, giving 2,3-dihydrofuran or 2,3-dihydropyrrole products, respectively, with excellent diastereoselectivity; and (III) the aerobic biomimetic oxidation of primary- and secondary alcohols to their respective aldehydes or ketones.

In the fifth chapter, XAS is used to elucidate the mechanisms of a Pd(II)-AmP-MCF-catalyzed lactonization reaction of acetylenic acids. The catalyst was known to deactivate during the reaction and the XAS studies identified the cause of this deactivation. A reactivation strategy was subsequently developed based on these findings.

In the sixth and final chapter, XAS is used to examine the activation mechanism of a ruthenium racemization catalyst and a ruthenium-acyl intermediate which had previously been speculated to be formed in the activation process was confirmed.

We report the first Fe-II-catalyzed biomimetic aerobic oxidation of alcohols. The principle of this oxidation, which involves several electron-transfer steps, is reminiscent of biological oxidation in the respiratory chain. The electron transfer from the alcohol to molecular oxygen occurs with the aid of three coupled catalytic redox systems, leading to a low-energy pathway. An iron transfer-hydrogenation complex was utilized as a substrate-selective dehydrogenation catalyst, along with an electron-rich quinone and an oxygen-activating Co(salen)-type complex as electron-transfer mediators. Various primary and secondary alcohols were oxidized in air to the corresponding aldehydes or ketones with this method in good to excellent yields.

Transition metal catalysis in modern organic synthesis has largely focused on noble transition metals like palladium, platinum and ruthenium. The toxicity and low abundance of these metals, however, has led to a rising focus on the development of the more sustainable base metals like iron, copper and nickel for use in catalysis. Iron is a particularly good candidate for this purpose due to its abundance, wide redox potential range, and the ease with which its properties can be tuned through the exploitation of its multiple oxidation states, electron spin states and redox potential. This is a fact made clear by all life on Earth, where iron is used as a cornerstone in the chemistry of living processes. In this mini review, we report on the general advancements in the field of iron catalysis in organic chemistry covering addition reactions, C-H activation, cross-coupling reactions, cycloadditions, isomerization and redox reactions.

Herein, we report the synthesis of 2,3-dihydropyrroles via an iron-catalyzed intramolecular nucleophilic cyclization of alpha-allenic sulfonamides. A highly diastereoselective variant of the reaction was also developed with the use of 1,2-disubstituted allenamides, which afforded 2,3-dihydropyrroles with diastereomeric ratios of >98:2. Insight into the mechanism was gained through a detailed DFT study, which elucidates the reaction mechanism and rationalizes the high chemoselectivity and diastereoselectivity.

The cause and mechanism of deactivation of a well-studied heterogeneous palladium(II) catalyst in the intramolecular lactonization of acetylenic acids to γ-alkylidene lactones have been investigated. It was shown that the deactivation was driven by the formation of reduced palladium species following the addition of the base triethylamine. In this work, X-ray absorption spectroscopy (XAS) was used to identify the palladium species and follow their evolution over the course of the reaction. It was also found that the choice of substrates has significant influences on the Pd species under the same reaction conditions. With these insights into the deactivation mechanism derived from XAS, different strategies were tested and illustrated to regain or maintain the active state of the catalyst. This information was further used to develop a new protocol, which can effectively prevent the deactivation of the catalyst and prolong its usage. 

Herein, we report a highly efficient iron-catalyzed intramolecular nucleophilic cyclization of alpha-allenols to furnish substituted 2,3-dihydrofurans under mild reaction conditions. A highly diastereoselective variant of the reaction was developed as well, giving diastereomeric ratios of up to 98:2. The combination of the iron-catalyzed cycloisomerization with enzymatic resolution afforded the 2,3-dihydrofuran in high ee. A detailed DFT study provides insight into the reaction mechanism and gives a rationalization for the high chemo-and diastereoselectivity.