A TEMPO‐Free Copper‐Catalyzed Aerobic Oxidation of Alcohols

The copper‐catalyzed aerobic oxidation of primary and secondary alcohols without an external N‐oxide co‐oxidant is described. The catalyst system is composed of a Cu/diamine complex inspired by the enzyme tyrosinase, along with dimethylaminopyridine (DMAP) or N‐methylimidazole (NMI). The Cu catalyst system works without 2,2,6,6‐tetramethyl‐l‐piperidinoxyl (TEMPO) at ambient pressure and temperature, and displays activity for un‐activated secondary alcohols, which remain a challenging substrate for catalytic aerobic systems. Our work underscores the importance of finding alternative mechanistic pathways for alcohol oxidation, which complement Cu/TEMPO systems, and demonstrate, in this case, a preference for the oxidation of activated secondary over primary alcohols.     

One-Pot Direct Oxidation of Primary Amines to Carboxylic Acids through Tandem ortho-Naphthoquinone-Catalyzed and TBHP-Promoted Oxidation Sequence

Biomimetic oxidation of primary amines to carboxylic acids has been developed where the copper-containing amine oxidase (CuAO)-like o-NQ-catalyzed aerobic oxidation was combined with the aldehyde dehydrogenase (ALDH)-like TBHP-mediated imine oxidation protocol. Notably, the current tandem oxidation strategy provides a new mechanistic insight into the imine intermediate and the seemingly simple TBHP-mediated oxidation pathways of imines. The developed metal-free amine oxidation protocol allows the use of molecular oxygen and TBHP, safe forms of oxidant that may appeal to the industrial application.     

Application and Mechanistic Studies of a Water‐Oxidation Catalyst in Alcohol Oxidation by Employing Oxygen‐Transfer Reagents

By using a dimeric ruthenium complex in combination with tert‐butyl hydrogen peroxide (TBHP) as stoichiometric oxidant, a mild and efficient protocol for the oxidation of secondary benzylic alcohols was obtained, thereby giving the corresponding ketones in high yields within 4 h. However, in the oxidation of aliphatic alcohols, the TBHP protocol suffered from low conversions owing to a competing Ru‐catalyzed disproportionation of the oxidant. Gratifyingly, by switching to Oxone (2 KHSO₅ ? KHSO₄ ? K₂SO₄ triple salt) as stoichiometric oxidant, a more efficient and robust system was obtained that allowed for the oxidation of a wide range of aliphatic and benzylic secondary alcohols, giving the corresponding ketones in excellent yields. The mechanism for these reactions is believed to involve a high‐valent Ru^V–oxo species. We provide support for such an intermediate by means of mechanistic studies.     

Batch‐ and Continuous‐Flow Aerobic Oxidation of 14‐Hydroxy Opioids to 1,3‐Oxazolidines—A Concise Synthesis of Noroxymorphone

14‐Hydroxymorphinone is converted to noroxymorphone, the immediate precursor of important opioid antagonists, such as naltrexone and naloxone, in a three‐step reaction sequence. The initial oxidation of the N‐methyl group in 14‐hydroxymorphinone with in situ generated colloidal palladium(0) as the catalyst and molecular oxygen as the terminal oxidant constitutes the key transformation in this new route. This oxidation results in the formation of an unexpected oxazolidine ring structure. Subsequent hydrolysis of the oxazolidine under reduced pressure followed by hydrogenation in a packed‐bed flow reactor using palladium(0) as the catalyst provides noroxymorphone in high purity and good overall yield. To overcome challenges associated with gas–liquid reactions with molecular oxygen, the key oxidation reaction was translated to a continuous‐flow process.     

Electrochemistry Broadens the Scope of Flavin Photocatalysis: Photoelectrocatalytic Oxidation of Unactivated Alcohols

Riboflavin‐derived photocatalysts have been extensively studied in the context of alcohol oxidation. However, to date, the scope of this catalytic methodology has been limited to benzyl alcohols. In this work, mechanistic understanding of flavin‐catalyzed oxidation reactions, in either the absence or presence of thiourea as a cocatalyst, was obtained. The mechanistic insights enabled development of an electrochemically driven photochemical oxidation of primary and secondary aliphatic alcohols using a pair of flavin and dialkylthiourea catalysts. Electrochemistry makes it possible to avoid using O₂ and an oxidant and generating H₂O₂ as a byproduct, both of which oxidatively degrade thiourea under the reaction conditions. This modification unlocks a new mechanistic pathway in which the oxidation of unactivated alcohols is achieved by thiyl radical mediated hydrogen‐atom abstraction.     

Cu‐Catalyzed Aerobic Oxidative Cyclizations of 3‐N‐Hydroxyamino‐1,2‐propadienes with Alcohols,Thiols, and Amines To Form α‐O‐, S‐, and N‐Substituted 4‐Methylquinoline Derivatives

A one‐pot, two‐step synthesis of α‐O‐, S‐, and N‐substituted 4‐methylquinoline derivatives through Cu‐catalyzed aerobic oxidations of N‐hydroxyaminoallenes with alcohols, thiols, and amines is described. This reaction sequence involves an initial oxidation of N‐hydroxyaminoallenes with NuH (Nu=OH, OR, NHR, and SR) to form 3‐substituted 2‐en‐1‐ones, followed by Brønsted acid catalyzed intramolecular cyclizations of the resulting products. Our mechanistic analysis suggests that the reactions proceed through a radical‐type mechanism rather than a typical nitrone‐intermediate route. The utility of this new Cu‐catalyzed reaction is shown by its applicability to the synthesis of several 2‐amino‐4‐methylquinoline derivatives, which are known to be key precursors to several bioactive molecules.     

Air Oxidation of N-Cyclopropylanilines

Air oxidation of N-cyclopropylanilines was shown to occur under either ambient conditions or accelerated conditions (warming or shining light) in an open container. A subsequent fragmentation resulted in formation of the corresponding acetamide. While potential mechanisms have been previously proposed, simple aerobic oxidation to β-hydroxy-propionamides in the absence of a radical promoter has not been previously reported.     

NMO⋅TPB: A Selectivity Variation on the Ley–Griffith TPAP Oxidation

A non‐hygroscopic tetraphenylborate salt of N‐methylmorpholine‐N‐oxide (NMO) is reported (NMO ? TPB), which modulates the standard Ley–Griffith oxidation such that benzylic and allylic alcohols are oxidised selectively. An attractive feature of this new protocol is that anhydrous conditions are not required for this selective tetra‐n‐propylammonium perruthenate (TPAP) oxidation, superseding the requirement of molecular sieves.     

Direct Access to β‐Fluorinated Aldehydes by Nitrite‐Modified Wacker Oxidation

An aldehyde‐selective Wacker‐type oxidation of allylic fluorides proceeds with a nitrite catalyst. The method represents a direct route to prepare β‐fluorinated aldehydes. Allylic fluorides bearing a variety of functional groups are transformed in high yield and very high regioselectivity. Additionally, the unpurified aldehyde products serve as versatile intermediates, thus enabling access to a diverse array of fluorinated building blocks. Preliminary mechanistic investigations suggest that inductive effects have a strong influence on the rate and regioselectivity of the oxidation.     

Synthesis and Asymmetric Oxidation of (Caranylsulfanyl)‐1H‐imidazoles

For the first time 2‐(cis‐caran‐4‐ylsulfanyl)‐1H‐imidazole, 1‐methyl‐2‐(cis‐caran‐4‐ylsulfanyl)‐1H‐imidazole, and 2‐(cis‐caran‐4‐ylsulfanyl)‐1H‐benzimidazole (carane=3,7,7‐trimethylbicyclo[4.1.0]heptane) were synthesized, and the asymmetric oxidation of these compounds was also carried out. It was shown that oxidation by the Bolm system and the modified system of Sharpless lead to corresponding sulfoxides with de values of 91–100%.     

Catalytic and Mechanistic Insights of the Low‐Temperature Selective Oxidation of Methane over Cu‐Promoted Fe‐ZSM‐5

The partial oxidation of methane to methanol presents one of the most challenging targets in catalysis. Although this is the focus of much research, until recently, approaches had proceeded at low catalytic rates (<10 h^?1), not resulted in a closed catalytic cycle, or were unable to produce methanol with a reasonable selectivity. Recent research has demonstrated, however, that a system composed of an iron‐ and copper‐containing zeolite is able to catalytically convert methane to methanol with turnover frequencies (TOFs) of over 14 000 h^?1 by using H₂O₂ as terminal oxidant. However, the precise roles of the catalyst and the full mechanistic cycle remain unclear. We hereby report a systematic study of the kinetic parameters and mechanistic features of the process, and present a reaction network consisting of the activation of methane, the formation of an activated hydroperoxy species, and the by‐production of hydroxyl radicals. The catalytic system in question results in a low‐energy methane activation route, and allows selective C₁‐oxidation to proceed under intrinsically mild reaction conditions.     

Factors That Affect the Nature of the Final Oxidation Products in “Peroxo‐Shunt” Reactions of Iron–Porphyrin Complexes

The present study focuses on the oxidation of the water‐soluble and water‐insoluble iron(III)–porphyrin complexes [Fe^III(TMPS)] and [Fe^III(TMP)] (TMPS=meso‐tetrakis(2,4,6‐trimethyl‐3‐sulfonatophenyl)porphyrinato, TMP=meso‐tetrakis(2,4,6‐trimethylphenyl)porphyrinato), respectively, by meta‐chloroperoxybenzoic acid (m‐CPBA) in aqueous methanol and aqueous acetonitrile solutions of varying acidity. With the application of a low‐temperature rapid‐scan UV/Vis spectroscopic technique, the complete spectral changes that accompany the formation and decomposition of the primary product of O? O bond cleavage in the acylperoxoiron(III)–porphyrin intermediate [(P)Fe^III? OOX] (P=porphyrin) were successfully recorded and characterized. The results clearly indicate that the O? O bond in m‐CPBA is heterolytically cleaved by the studied iron(III)–porphyrin complexes independent of the acidity of the reaction medium. The existence of two different oxidation products under acidic and basic conditions is suggested not to be the result of a mechanistic changeover in the mode of O? O bond cleavage on going from low to high pH values, but rather the effect of environmental changes on the actual product of the O? O bond cleavage in [(P)Fe^III? OOX]. The oxoiron(IV)–porphyrin cation radical formed as a primary oxidation product over the entire pH range can undergo a one‐ or two‐electron reduction depending on the selected reaction conditions. The present study provides valuable information for the interpretation and improved understanding of results obtained in product‐analysis experiments.     

Catalytic Oxidation of Furan and Hydrofuran Compounds. 7. Production of 2(5H)-Furanone by Oxidation of Furfural with Hydrogen Peroxide and Some of Its Transformations in Aqueous Solutions

Data on the synthesis of 2(5H)-furanone by the oxidation of furfural with aqueous hydrogen peroxide under the conditions of autocatalysis by the accumulating acids and also in the presence of catalytic amounts of Cr(VI) and Mo(VI) compounds are presented. Some transformations of 2(5H)-furanone in aqueous solutions are studied: hydrolysis, oxidation by potassium permanganate, complex formation with the ions of certain d-metals.     

Mechanistic Insights into Selectivity Control for Heterogeneous Olefin Oxidation: Styrene Oxidation on Au(111)

We demonstrate that intermolecular interactions, controlled by both oxygen and styrene coverage, alter reaction selectivity for styrene oxidation on oxygen‐covered Au(111). Several partial oxidation products are formed—styrene oxide, acetophenone, benzoic acid, benzeneacetic acid, and phenylketene—in competition with combustion. The maximum ratio of the yields of styrene oxide to the total CO₂ produced is obtained for the maximum styrene coverage for the first two layers (0.28 ML) adsorbed on Au(111) precovered with 0.2 ML of O. Furthermore, our reactivity and infrared studies support a mechanism whereby styrene oxidation proceeds via two oxametallacycle intermediates which, under oxygen‐lean conditions, lead to the formation of styrene oxide, acetophenone, and phenylketene. Benzoate, identified on the basis of infrared reflection absorption spectroscopy, is converted into benzoic acid during temperature‐programmed reaction. These results demonstrate the ability to tune the epoxidation selectivity using reactant coverages and provide important mechanistic insight into styrene oxidation reactions.     

Simple and Efficient Ruthenium‐Catalyzed Oxidation of Primary Alcohols with Molecular Oxygen

Oxidative transformations utilizing molecular oxygen (O₂) as the stoichiometric oxidant are of paramount importance in organic synthesis from ecological and economical perspectives. Alcohol oxidation reactions that employ O₂ are scarce in homogeneous catalysis and the efficacy of such systems has been constrained by limited substrate scope (most involve secondary alcohol oxidation) or practical factors, such as the need for an excess of base or an additive. Catalytic systems employing O₂ as the “primary” oxidant, in the absence of any additive, are rare. A solution to this longstanding issue is offered by the development of an efficient ruthenium‐catalyzed oxidation protocol, which enables smooth oxidation of a wide variety of primary, as well as secondary benzylic, allylic, heterocyclic, and aliphatic, alcohols with molecular oxygen as the primary oxidant and without any base or hydrogen‐ or electron‐transfer agents. Most importantly, a high degree of selectivity during alcohol oxidation has been predicted for complex settings. Preliminary mechanistic studies including ¹⁸O labeling established the in situ formation of an oxo–ruthenium intermediate as the active catalytic species in the cycle and involvement of a two‐electron hydride transfer in the rate‐limiting step.     

Mechanistic Studies on the Roles of the Oxidant and Hydrogen Bonding in Determining the Selectivity in Alkene Oxidation in the Presence of Molybdenum Catalysts

When the molybdenum oxo(peroxo) acetylide complex [CpMo(O? O)(O)C?CPh] is used as a catalyst for the oxidation of olefins, completely different product selectivity is obtained depending on the oxidant employed. When tert‐butyl hydroperoxide (TBHP, 5.5 M ) in dodecane is used as the oxidant for the oxidation of cyclohexene, cyclohexene oxide is formed with high selectivity. However, when H₂O₂ is used as the oxidant, the corresponding cis‐1,2‐diol is formed as the major product. Calculations performed by using density functional theory revealed the nature of the different competing mechanisms operating during the catalysis process and also provided an insight into the influence of the oxidant and hydrogen bonding on the catalysis process. The mechanistic investigations can therefore serve as a guide in the design of molybdenum‐based catalysts for the oxidation of olefins.     

Real and Virtual Degrees of Oxidation of d Elements in Coordination Compounds

The "degree of oxidation" or "state of oxidation" are extremely long-lived concepts in inorganic and coordination chemistry. In this paper such concepts as real and virtual degrees of oxidation are introduced, and possible ways of using them for the production of new materials are demonstrated. The concepts are undoubtedly related in the closest manner to coordination chemistry. The degrees of oxidation of elements of the transfermium group are examined, and this provides the possibility of predicting the degrees of oxidation of these elements. It was found that the d ⁵, d ⁷, d ⁹ elements do not form coordination compounds with an overall negative electric charge.     

Metal‐Free 2,2,6,6‐Tetramethylpiperidin‐1‐yloxy Radical (TEMPO) Catalyzed Aerobic Oxidation of Hydroxylamines and Alkoxyamines to Oximes and Oxime Ethers

TEMPO‐Mediated oxidation of hydroxylamines (=hydroxyamines) and alkoxyamines to the corresponding oxime derivatives is reported (TEMPO=2,2,6,6‐tetramethylpiperidin‐1‐yloxy radical; Scheme 2). These environmentally benign oxidations proceed in good to excellent yields (Table 1). For alkoxyamines, oxidation to the corresponding oxime ethers can be performed by using dioxygen as a terminal oxidant in the presence of 5–10 mol‐% of TEMPO or 4‐substituted derivatives thereof as a catalyst (Scheme 3 and Table 2). Importantly, benzyl bromides can directly be transformed to oxime ethers via in situ alkoxyamine formation by a nucleophilic substitution followed by TEMPO‐mediated oxidation (Scheme 4 and Table 3).     

Kinetic Resolution of sec‐Thiols by Enantioselective Oxidation with Rationally Engineered 5‐(Hydroxymethyl)furfural Oxidase

Various flavoprotein oxidases were recently shown to oxidize primary thiols. Herein, this reactivity is extended to sec‐thiols by using structure‐guided engineering of 5‐(hydroxymethyl)furfural oxidase (HMFO). The variants obtained were employed for the oxidative kinetic resolution of racemic sec‐thiols, thus yielding the corresponding thioketones and nonreacted R‐configured thiols with excellent enantioselectivities (E≥200). The engineering strategy applied went beyond the classic approach of replacing bulky amino acid residues with smaller ones, as the active site was additionally enlarged by a newly introduced Thr residue. This residue established a hydrogen‐bonding interaction with the substrates, as verified in the crystal structure of the variant. These strategies unlocked HMFO variants for the enantioselective oxidation of a range of sec‐thiols.     

Efficient Nazarov Cyclization/Wagner–Meerwein Rearrangement Terminated by a CuII‐Promoted Oxidation: Synthesis of 4‐Alkylidene Cyclopentenones

The discovery and elucidation of a new Nazarov cyclization/Wagner–Meerwein rearrangement/oxidation sequence is described that constitutes an efficient strategy for the synthesis of 4‐alkylidene cyclopentenones. DFT computations and EPR experiments were conducted to gain further mechanistic insight into the reaction pathways.