Terminal Oxidant Research Articles

Manganese catalyzed direct regio- and stereoselective hydroxylation of 5α- and 5β-androstane derivatives

Herewith we report late-stage catalytic selective oxidative functionalization of several steroids with a common gonane core, namely androstane derivatives 5α-androsterone-3-acetate, 5β-androstan-17β-ol-3-one (etiocholan-17β-ol-3-one), 17β-acetoxy-5β-androstan-3-one, and 5β-pregnane-3,20-dione, at C–H groups in the presence of chiral bis-amino-bis-pyridylmethyl and structurally related Mn complexes, using H2O2 as terminal oxidant. Depending on the steric demand and absolute chirality of the catalyst, mono-hydroxylation at A, B, or C rings is achieved in up to 58% isolated yield. Strongly hydrogen-bond donating solvent hexafluoroisopropanol (HFIP) effectively protects the C17–OH group in etiocholan-17β-ol-3-one from ketonization, thus providing an opportunity to obtain 6,17- and 12,17-dihydroxy androstane derivatives without using protecting groups.

Palladium Catalyzed Aerobic Oxidative Amination of Alkenes

AbstractAmines are widely applied in the chemical and pharmaceutical industries, and the development of synthetic methods for their preparation is driven by their importance. The amination of alkenes is a direct and efficient method for the construction of amines, of which oxidative amination is more valuable because it can give the desired products with greater functionality and flexibility. In oxidative amination, using molecular oxygen (O2) as a terminal oxidant has promising industrial application prospects. In recent years, the palladium‐catalyzed aerobic oxidation of alkenes has seen significant progress, and its related research has also been extended to the aerobic oxidative amination of alkenes. The corresponding oxidation systems have been developed from early research involving the introduction of cocatalysts to the more recent systems which utilize auxiliary ligands instead of cocatalysts. In this review, the advancements in the palladium‐catalyzed aerobic oxidative amination of monoalkenes and conjugated dienes over the last two decades are discussed, with emphasis on aerobic oxidation process and their associated mechanisms.

Hydrogen atom abstraction by a high-spin [FeIII=S] complex

Iron sulfur clusters are critical to a plethora of biological processes; however, little is known about the elementary unit of these clusters, namely the [Fe=S]n+ fragment. Here, we report the synthesis and characterization of a terminal iron sulfido complex. Despite its high spin (S = 5/2) ground state, structural, spectroscopic, and computational characterization provide evidence for iron sulfur multiple bond character. Intriguingly, the complex reacts with additional sulfur to afford an S = 3/2 iron(III) disulfido (S2 2-) complex. Preliminary studies reveal that the sulfido complex reacts with dihydroanthracene to afford an iron(II) hydrosulfido complex, akin to the reactivity of iron oxo complexes. By contrast, there is no reaction with the disulfido complex. These results provide important insight into the nature of the iron sulfide unit.

Merging Cu(I) and Cu(II) Photocatalysis: Development of a Versatile Oxohalogenation Protocol for the Sequential Cu(II)/Cu(I)-Catalyzed Oxoallylation of Vinylarenes.

A sequential photocatalytic strategy is developed via the merger of Cu(II)/Cu(I)-catalytic cycles for the oxoallylation of vinyl arenes via α-haloketones. The initial Cu(II)-photocatalyzed oxohalogenation exploits ligand-to-metal charge transfer (LMCT) to generate halide radicals from acyl halides utilizing air as a terminal oxidant and can be employed for the late-stage modification of pharmaceuticals and agrochemicals. α-Bromoketones obtained this way can be subsequently subjected to a one-pot Cu(I)-photocatalyzed allylation. This sequential photocatalysis proceeds in a highly regio- and chemoselective fashion and is inconsequential to the electronic nature of styrenes.

Synthesis, characterization and application of a highly dispersed and reactive hypervalent iodine(V)/polyvinylpyrrolidone dendrimer nanocomposite: Hetero- vs. homo-intermolecular secondary O---I bonds

Polyvinylpyrrolidone (PVP) assisted aerobic oxidation of bulk iodosylbenzene or hydrolysis/oxidation of iodobenzene diacetate under mild conditions leading to the formation of nanostructured iodylbenzene is reported. AFM and FESEM-EDX analyses confirmed the formation of dendrimer iodylbenzene-polyvinylpyrrolidone nanocomposite (PhIO2-PVP) through the two top-down approaches. The formation of PhIO2 was confirmed by 1H NMR spectroscopy. Strong interactions between iodylbenzene molecules and the polymer through secondary intermolecular O---I bonds was evident from the large difference between the morphology of PVP (cubic) and PhIO2-PVP (dendrimer) nanoparticles. FESEM images showed a maximum width and length of 70 and 1000 nm for the dendrimers, respectively. The dual role played by PVP, i.e., facilitating the oxidation of I(III) to I(V) and stabilization the hypervalent I(V) compound was attributed to the formation of strong secondary hetero-intermolecular O---I bonds, between the polymer and iodine centre. The very fine aqueous and dichloromethane suspensions of PhIO2-PVP were indistinguishable to the naked eye. Efficient direct oxidation of cyclohexene and methylene blue with PhIO2-PVP at room temperature and a short reaction time provided evidence of significantly increased reactivity of PhIO2-PVP compared to that of the bulk oxidant. PhIO2-PVP was also used in the oxidation of methyl phenyl sulfide and styrene in water and dichloroethane, using water soluble and insoluble metalloporphyrins, respectively. The former led to the formation of the corresponding sulfoxide as the sole product in the two solvents. In addition to styrene oxide formed in both solvents, benzaldehyde was also formed with a selectivity of 24% in water. Almost complete oxidation of the organic substrates was observed in dichloroethane. The results of this study show that the nanostructured iodine(V) compound can be used as an efficient terminal oxidant in biomimetic oxidations.

Methane Conversion to Methanol Using Au/ZSM-5 is Promoted by Carbon

The oxidation of methane using molecular oxygen as the terminal oxidant, over a Au/ZSM-5 catalyst, has been previously shown to produce methanol and acetic acid as products. We now show that this reaction is significantly enhanced by the addition of a range of carbon additives. Isotopic 13C-labeled studies and corresponding investigation into the activity of the carbon materials alone reveal that nearly all the methanol produced is derived from methane oxidation, with a negligible contribution attributed to the carbon additives, while further study identified carbon as the primary source of acetic acid, which was observed as a minor product. Gas phase CO is not observed as a product in the reaction of Au/ZSM-5 with CH4 + O2, and in reactions with added CO, not all the CO is converted. We, therefore, conclude that the effect observed with the carbon additive is not due to the in situ production of gas phase CO as a reaction intermediate. Rather, we postulate that the effect derives from the oxidation of the surface of the carbon in the aqueous reaction mixture and the interaction of the oxidized carbon surface with Au/ZSM-5. The reactivity of carbon in this reaction at 240 °C is unexpected, and the presence of water is required to observe the effect.

Direct Anodic Conversion of 4-Hydroxybenzaldehydes into Benzoquinones

A novel electrosynthetic protocol for the direct conversion of easily accessible 4-hydroxybenzaldehydes into valuable benzoquinones is reported. The transformation is enabled through anodic oxidation and is performed in a reagent-free manner devoid of terminal oxidants and redox mediators to effectively minimize waste. Environmentally benign and inexpensive graphite serves as a metal-free anode material. A broad range of substituents, including halogens, are tolerated in this electrochemical protocol, and the quinones are selectively accessible in yields up to 99%. Furthermore, the compatibility with electrochemical flow synthesis is demonstrated. Moreover, the flow protocol is successfully applied to the biopolymer lignosulfonate and provides quinones in yields up to 7.6 wt%. A mechanistic proposal for this Dakin-type reaction is offered. The sustainability and synthetic utility are evaluated quantitatively and compared to established protocols by application of different green chemistry metrics.

Photocatalytic Aerobic Cyclization of N-Propargylamides Enabled by Selenium-π-Acid Catalysis.

A dual catalytic approach combining photocatalyst and selenium-π-acid synergy has been used to cyclized of N-propargylamides. This method offers readily access to oxazole aldehydes under chemical oxidant-free conditions with low catalyst loadings, where air acts as a terminal and gratuitous oxidant. The reaction is demonstrated with a range of substrates, including aryl and alkyl propargyl amides, and in the late-stage functionalization of several amide-containing drug molecules. Mechanistic studies suggest that the acridinium catalyst is able to oxidize diselenide and generate singlet oxygen (1 O2 ), which is responsible for this transformation.

Characterization of Guaiacol Peroxidase Enzyme from Carambola Fruit

Carambola is a fruit grown in tropical and subtropical regions of the world. Natural antioxidants including vitamin C, carotenoids, and certain phenolic substances are abundant in carambola fruit. As antioxidants support health by acting as nutraceutical and functional food additives, they help preserve food by preventing oxidation processes. The oxidation of various organic or inorganic substrates by hydrogen peroxide or organic peroxides as terminal oxidants is a process in which peroxidase, which is abundantly present in fruits and vegetables, participates. In this study, guaiacol peroxidase enzyme from carambola fruit was partially purified and characterized. Purification procedure made up the homogenate preparation, ammonium sulfate precipitation, and dialysis. After purification, optimum ionic strength, pH and substrate concentration were investigated. These values were determined as 200 mM Tris, pH: 7.5, 7.5 mM H2O2 and 15 mM guaiacol for carambola fruit guaiacol peroxidase enzyme, respectively.

Arene C–H Amination with N-Heteroarenes by Catalytic DDQ Photocatalysis

Arene C-H aminations using catalytic amounts of a 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) photocatalyst are described. Benzene, which has an oxidation potential of 2.48 V (vs SCE), was functionalized by pyrazoles, triazoles, tetrazoles, purines, and tert-butoxycarbonyl amine. Arenes underwent amination via a combination of ultraviolet (UV) light and a DDQ photocatalyst without a typical co-oxidant. Although the mechanism remains an open question, DDQH2, which is generated from DDQ after oxidation, is reactivated to DDQ under UV light irradiation conditions, possibly with the assistance of adventitious O2 and/or a solvent as the terminal oxidant(s) in this system.

A comprehensive genomic analysis provides insights on the high environmental adaptability of Acinetobacter strains.

Acinetobacter is ubiquitous, and it has a high species diversity and a complex evolutionary pattern. To elucidate the mechanism of its high ability to adapt to various environment, 312 genomes of Acinetobacter strains were analyzed using the phylogenomic and comparative genomics methods. It was revealed that the Acinetobacter genus has an open pan-genome and strong genome plasticity. The pan-genome consists of 47,500 genes, with 818 shared by all the genomes of Acinetobacter, while 22,291 are unique genes. Although Acinetobacter strains do not have a complete glycolytic pathway to directly utilize glucose as carbon source, most of them harbored the n-alkane-degrading genes alkB/alkM (97.1% of tested strains) and almA (96.7% of tested strains), which were responsible for medium-and long-chain n-alkane terminal oxidation reaction, respectively. Most Acinetobacter strains also have catA (93.3% of tested strains) and benAB (92.0% of tested strains) genes that can degrade the aromatic compounds catechol and benzoic acid, respectively. These abilities enable the Acinetobacter strains to easily obtain carbon and energy sources from their environment for survival. The Acinetobacter strains can manage osmotic pressure by accumulating potassium and compatible solutes, including betaine, mannitol, trehalose, glutamic acid, and proline. They respond to oxidative stress by synthesizing superoxide dismutase, catalase, disulfide isomerase, and methionine sulfoxide reductase that repair the damage caused by reactive oxygen species. In addition, most Acinetobacter strains contain many efflux pump genes and resistance genes to manage antibiotic stress and can synthesize a variety of secondary metabolites, including arylpolyene, β-lactone and siderophores among others, to adapt to their environment. These genes enable Acinetobacter strains to survive extreme stresses. The genome of each Acinetobacter strain contained different numbers of prophages (0-12) and genomic islands (GIs) (6-70), and genes related to antibiotic resistance were found in the GIs. The phylogenetic analysis revealed that the alkM and almA genes have a similar evolutionary position with the core genome, indicating that they may have been acquired by vertical gene transfer from their ancestor, while catA, benA, benB and the antibiotic resistance genes could have been acquired by horizontal gene transfer from the other organisms.

N,N’‐Difluoro‐2,2’‐bipyridinium Bis(tetrafluoroborate): a New Terminal Oxidant for Iodoarene‐catalyzed Fluorination Reactions

AbstractA new N−F reagent, N,N′‐difluoro‐2,2′‐bipyridinium bis(tetrafluoroborate), for iodoarene‐catalyzed fluorination reactions as a terminal oxidant is reported. This reaction is effective for the fluorination of simple alkenes, aromatic alkenes and 1,3‐dicarbonyl compounds, giving 1,2‐difluorinated alkanes, geminal difluorinated compounds, 2‐fluorinated‐1,3‐dicarbonyl compounds in good to high yields, respectively. This is a useful fluorination reaction that not only improves the issues of the fluorination reaction using conventional mCPBA as a terminal oxidant but also constructs a simpler catalytic cycle. The present N−F reagent can be recovered as 2,2’‐bipyridine.

Visible Light-Induced Oxidation of Alcohols by a Luminescent Osmium(VI) Nitrido Complex: Evidence for the Generation of PhIO+ as a Highly Active Oxidant in the Presence of PhIO

Although alcohols are readily oxidized by a variety of oxidants, their oxidation by metal nitrido complexes is yet to be studied. We report herein visible-light-induced oxidation of primary and secondary alcohols to carbonyl compounds by a strongly luminescent osmium(VI) nitrido complex (OsN). The proposed mechanism involves initial rate-limiting hydrogen-atom transfer (HAT) from the α-carbon of the alcohol to OsN*. Attempts to develop catalytic oxidation of alcohols by OsN* using PhIO as the terminal oxidant resulted in the formation of novel osmium(IV) iminato complexes in which the nitrido ligand is bonded to a δ-carbon of the alcohol. Experimental and theoretical studies suggest that OsN* is reductively quenched by PhIO to generate PhIO+, which is a highly active oxidant that readily undergoes α- and δ-C-H activation of alcohols.

Selective oxidation of vinylbenzenes & acyloins in the presence of silver catalyst using molecular oxygen as terminal oxidant

Selective oxidation of styrene to benzaldehyde continues to be a quest for synthetic chemists. A number of transition metal based, metal free, nanocomposite-based catalysts have been developed for this transformation. We hereby report the oxidation of styrene into corresponding benzaldehydes using molecular oxygen as oxidant in the presence of catalytic amount of Ag2O. The reaction proceeded with a well-known oxidation of styrene-to-styrene oxide giving intermediates which lead to decarboxylative generation of aldehydes. One such intermediate was hydroxyketone. In view of the formation of hydroxyketone intermediate, we explored the oxidative dehomologation of α-hydroxy ketone via decarboxylation of 2-oxo-2-phenylacetic acid into benzoic acid using the same strategy. Both the reactions exhibited high functional group tolerance and a broad substrate scope.

Green Selective Oxidation of Substituted Indoles Catalyzed by CuCl.

An efficient and convenient method for copper-catalyzed green selective oxidative functionalization of indoles using atmospheric O2 as the terminal oxidant has been developed. This method can be applied to Witkop oxidation and oxidation homocoupling of indoles with good functional group tolerance and substrate scope. Various indoles reacted with molecular oxygen to give the corresponding products in moderate to good yields. A gram-scale experiment can be successfully operated. This protocol provides a sustainable and practical strategy for green oxidation of indoles. By employing this method, multifarious structurally important 2-ketoacetanilide derivatives were efficiently synthesized from simple indoles and complex bioactive molecule derivatives.

Rhodium(III‐Catalyzed C8‐Selective C−H Alkenylation and Alkylation of 1, 2, 3, 4‐Tetrahydroquinolines with Styrenes and Allylic Alcohols

AbstractRh(III)‐catalyzed chelation‐assisted C8‐selective C−H alkenylation and alkylation of 1,2,3,4‐tretrahydroquinolines with styrenes and allylic alcohols have been realized. The cationic Rh(III) catalytic system in combination with a catalytic amount of copper acetate uses oxygen as the terminal oxidant and catalyzes the stereoselective C8‐alkenylation of 1,2,3,4‐tetrahydroquinolines with styrenes to give the corresponding products in 56–93% yields with wide substrate scope and broad functional group compatibility. The reaction can be scaled up. Moreover, this protocol can be extended to the C8‐alkylation of 1,2,3,4‐tetrahydroquinolines with allylic alcohols, providing access to various 8‐(3‐oxoalkyl)‐1,2,3,4‐tetrahydroquinolines in 77–90% yields. The selection of N‐directing group is essential for catalysis, and the readily installable and removable N‐(2‐pyrimidyl) group proves to be optimal choice. Preliminary mechanistic studies are performed to gain insights into the reaction mechanism.magnified image

Recent Advancements on Metal-Free Vicinal Diamination of Alkenes: Synthetic Strategies and Mechanistic Insights.

The oxidative aminative vicinal difunctionalization of alkenes or related chemical feedstocks has emerged as sustainable and multipurpose strategies that can efficiently construct two -N bonds, and simultaneously prepare the synthetically fascinating molecules and catalysis in organic synthesis that typically required multi-step reactions. This review summarized the impressive breakthroughs on synthetic methodologies (2015-2022) documented especially over inter/intra-molecular vicinal diamination of alkenes with electron-rich or deficient diverse nitrogen sources. These unprecedented strategies predominantly involved iodine-based reagents/catalysts, which resent the interest of organic chemists due to their impressive role as flexible, non-toxic, and environmentally friendly reagents, resulting in a wide variety of synthetically useful organic molecules. Moreover, the information collected also describes the significant role of catalyst, terminal oxidant, substrate scope, synthetic applications, and their unsuccessful results to highlight the limitations. Special emphasis has been given to proposed mechanistic pathways to determine the key factors governing the issues of regioselectivity, enantioselectivity, and diastereoselectivity ratios.

Photoinduced Cerium-Mediated Decarboxylative Alkylation Cascade Cyclization of N-arylacrylamides and N-acryl-2-aryl benzimidazoles.

A mild and versatile cerium-mediated decarboxylative strategy for sequential alkylation/cyclization was developed for the synthesis of quaternary oxindoles and benzimidazo[2,1-a]isoquinolin-6(5H)-ones via photoinduced-LMCT. This operationally simple procedure relies on inexpensive and feedstock carboxylic acids as alkyl radical surrogates and aerial molecular oxygen as the terminal oxidant. This mild and atom economical protocol showed viability with a wide range of alkyl carboxylic acids (1° to 3° acids) as coupling partners and also allows the late-stage modification of pharmaceutically-important acids. Mechanistic studies revealed the reaction to follow radical pathway, while the decarboxylative event was studied by in situ FTIR.

Palladium-Catalyzed C-H Allylation/Annulation Reaction of Amides and Allylic Alcohols: Regioselective Construction of Vinyl-Substituted 3,4-Dihydroisoquinolones.

A palladium-catalyzed highly regioselective C-H allylation/annulation reaction of N-sulfonyl amides with secondary or tertiary allylic alcohols has been developed to construct 3,4-dihydroisoquinolones bearing a synthetically valuable vinyl substituent. This cascade cyclization approach of allylic alcohols involving C-H allylation has not been reported previously. The commercially available allylic alcohol substrates, the only by-product of water, and the used terminal oxidant of O2 provide environmentally benign advantages.

Hydrogen Bonding-Assisted and Nonheme Manganese-Catalyzed Remote Hydroxylation of C-H Bonds in Nitrogen-Containing Molecules.

The development of catalytic systems capable of oxygenating unactivated C-H bonds with excellent site-selectivity and functional group tolerance under mild conditions remains a challenge. Inspired by the secondary coordination sphere (SCS) hydrogen bonding in metallooxygenases, reported herein is an SCS solvent hydrogen bonding strategy that employs 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a strong hydrogen bond donor solvent to enable remote C-H hydroxylation in the presence of basic aza-heteroaromatic rings with a low loading of a readily available and inexpensive manganese complex as a catalyst and hydrogen peroxide as a terminal oxidant. We demonstrate that this strategy represents a promising compliment to the current state-of-the-art protection approaches that rely on precomplexation with strong Lewis and/or Brønsted acids. Mechanistic studies with experimental and theoretical approaches reveal the existence of a strong hydrogen bonding between the nitrogen-containing substrate and HFIP, which prevents the catalyst deactivation by nitrogen binding and deactivates the basic nitrogen atom toward oxygen atom transfer and the α-C-H bonds adjacent to the nitrogen center toward H-atom abstraction. Moreover, the hydrogen bonding exerted by HFIP has also been demonstrated not only to facilitate the O-O bond heterolytic cleavage of a putative MnIII-OOH precursor to generate MnV(O)(OC(O)CH2Br) as an active oxidant but also to affect the stability and the activity of MnV(O)(OC(O)CH2Br).