A manganese-based catalyst system for general oxidation of unactivated olefins, alkanes, and alcohols.

Non-noble metal-based catalyst systems consisting of inexpensive manganese salts, picolinic acid and various heterocycles enable epoxidation of the challenging (terminal) unactivated olefins, selective C-H oxidation of unactivated alkanes, and O-H oxidation of secondary alcohols with aqueous hydrogen peroxide. In the presence of the in situ generated optimal manganese catalyst, epoxides are generated with up to 81% yield from alkenes and ketone products with up to 51% yield from unactivated alkanes. This convenient protocol allows the formation of the desired products under ambient conditions (room temperature, 1 bar) by employing only a slight excess of hydrogen peroxide with 2,3-butadione as a sub-stoichiometric additive.

Unprecedented Mo3S4 cluster-catalyzed radical C-C cross-coupling reactions of aryl alkynes and acrylates.

A new method for the generation of benzyl radicals from terminal aromatic alkynes has been developed, which allows the direct cross coupling with acrylate derivatives. Our additive-free protocol employs air-stable diamino Mo3S4 cubane-type cluster catalysts in the presence of hydrogen. A sulfur-centered cluster catalysis mechanism for benzyl radical formation is proposed based on catalytic and stoichiometric experiments. The process starts with the cluster hydrogen activation to form a bis(hydrosulfido) [Mo3(µ3-S)(µ-S)(µ-SH)2Cl3(dmen)3]+ intermediate. The reaction of various aromatic terminal alkynes containing different functionalities with a series of acrylates affords the corresponding Giese-type radical addition products.

Synthesis of piperidines and pyridine from furfural over a surface single-atom alloy Ru1CoNP catalyst.

The sustainable production of value-added N-heterocycles from available biomass allows to reduce the reliance on fossil resources and creates possibilities for economically and ecologically improved synthesis of fine and bulk chemicals. Herein, we present a unique Ru1CoNP/HAP surface single-atom alloy (SSAA) catalyst, which enables a new type of transformation from the bio-based platform chemical furfural to give N-heterocyclic piperidine. In the presence of NH3 and H2, the desired product is formed under mild conditions with a yield up to 93%. Kinetic studies show that the formation of piperidine proceeds via a series of reaction steps. Initially, in this cascade process, furfural amination to furfurylamine takes place, followed by hydrogenation to tetrahydrofurfurylamine (THFAM) and then ring rearrangement to piperidine. DFT calculations suggest that the Ru1CoNP SSAA structure facilitates the direct ring opening of THFAM resulting in 5-amino-1-pentanol which is quickly converted to piperidine. The value of the presented catalytic strategy is highlighted by the synthesis of an actual drug, alkylated piperidines, and pyridine.

Applying green chemistry principles to iron catalysis: mild and selective domino synthesis of pyrroles from nitroarenes.

An efficient and general cascade synthesis of pyrroles from nitroarenes using an acid-tolerant homogeneous iron catalyst is presented. Initial (transfer) hydrogenation using the commercially available iron-Tetraphos catalyst is followed by acid catalysed Paal-Knorr condensation. Both formic acid and molecular hydrogen can be used as green reductants in this process. Particularly, under transfer hydrogenation conditions, the homogeneous catalyst shows remarkable reactivity at low temperatures, high functional group tolerance and excellent chemoselectivity transforming a wide variety of substrates. Compared to classical heterogeneous catalysts, this system presents complementing reactivity, showing none of the typical side reactions such as dehalogenation, debenzylation, arene or olefin hydrogenation. It thereby enhances the chemical toolbox in terms of orthogonal reactivity. The methodology was successfully applied to the late-stage modification of multi-functional drug(-like) molecules as well as to the one-pot synthesis of the bioactive agent BM-635.

Water-Promoted Carbon-Carbon Bond Cleavage Employing a Reusable Fe Single-Atom Catalyst.

The development of methods for selective cleavage reactions of thermodynamically stable C-C/C=C bonds in a green manner is a challenging research field which is largely unexplored. Herein, we present a heterogeneous Fe-N-C catalyst with highly dispersed iron centers that allows for the oxidative C-C/C=C bond cleavage of amines, secondary alcohols, ketones, and olefins in the presence of air (O2 ) and water (H2 O). Mechanistic studies reveal the presence of water to be essential for the performance of the Fe-N-C system, boosting the product yield from <1 % to >90 %. Combined spectroscopic characterizations and control experiments suggest the singlet 1 O2 and hydroxide species generated from O2 and H2 O, respectively, take selectively part in the C-C bond cleavage. The broad applicability (>40 examples) even for complex drugs as well as high activity, selectivity, and durability under comparably mild conditions highlight this unique catalytic system.

Bis(N-Heterocyclic Carbene) Manganese(I) Complexes: Efficient and Simple Hydrogenation Catalysts.

The use of bis(NHC) manganese(I) complexes 3 as catalysts for the hydrogenation of esters was investigated. For that purpose, a series of complexes has been synthesized via an improved two step procedure utilizing bis(NHC)-BEt3 adducts. By applying complexes 3 with KHBEt3 as additive, various aromatic and aliphatic esters were hydrogenated successfully at mild temperatures and low catalyst loadings, highlighting the efficiency of the novel catalytic system. The versatility of the developed catalytic system was further demonstrated by the hydrogenation of other substrate classes like ketones, nitriles, N-heteroarenes and alkenes. Mechanistic experiments and DFT calculations indicate an inner sphere mechanism with the loss of one CO ligand and reveal the role of BEt3 as cocatalyst.

Hydrogenation of Carboxylic Acids, Esters, and Related Compounds over Heterogeneous Catalysts: A Step toward Sustainable and Carbon-Neutral Processes.

The catalytic hydrogenation of esters and carboxylic acids represents a fundamental and important class of organic transformations, which is widely applied in energy, environmental, agricultural, and pharmaceutical industries. Due to the low reactivity of the carbonyl group in carboxylic acids and esters, this type of reaction is, however, rather challenging. Hence, specifically active catalysts are required to achieve a satisfactory yield. Nevertheless, in recent years, remarkable progress has been made on the development of catalysts for this type of reaction, especially heterogeneous catalysts, which are generally dominating in industry. Here in this review, we discuss the recent breakthroughs as well as milestone achievements for the hydrogenation of industrially important carboxylic acids and esters utilizing heterogeneous catalysts. In addition, related catalytic hydrogenations that are considered of importance for the development of cleaner energy technologies and a circular chemical industry will be discussed in detail. Special attention is paid to the insights into the structure-activity relationship, which will help the readers to develop rational design strategies for the synthesis of more efficient heterogeneous catalysts.

Efficient Hydrogenation of N-Heterocycles Catalyzed by NNP-Manganese(I) Pincer Complexes at Ambient Temperature.

Manganese-catalyzed hydrogenation reactions have aroused widespread interest in recent years. Among the catalytic systems described, especially PNP- and NNP-Mn pincer catalysts have been reported for the hydrogenation of aldehydes, ketones, nitriles, aldimines and esters. Furthermore, NNP-Mn pincer compounds are efficient catalysts for the hydrogenolysis of less reactive amides, ureas, carbonates, and carbamates. Herein, the synthesis and application of specific imidazolylaminophosphine ligands and the corresponding Mn pincer complexes are described. These new catalysts have been characterized and studied by a combination of experimental and theoretical investigations, and their catalytic activities have been tested in several hydrogenation reactions with good to excellent performance. Especially, the reduction of N-heterocycles can be performed under very mild conditions.

Low-Valent Molybdenum PNP Pincer Complexes as Catalysts for the Semihydrogenation of Alkynes.

Low-valent molybdenum PNP pincer complexes were studied as catalysts for the semihydrogenation of alkynes. For that purpose, tBu-substituted PNP complexes PNP tBuMo(CO)2 (6a) and PNP tBuMo(CO)3 (6c) and the NNP complex NNP iPrMo(CO)2(PPh3) ((rac)-7) were synthesized and characterized. By utilizing the cyclohexyl-substituted complex PNPCyMo(CO)2(CH3CN) (5a), several diphenylacetylene derivatives are transformed to the corresponding (Z)-alkenes with good to very good diastereoselectivities (up to 91:9). Mechanistic experiments indicate an outer-sphere mechanism including metal-ligand cooperativity.

Diastereoselective hydrogenation of arenes and pyridines using supported ruthenium nanoparticles under mild conditions.

A convenient and practical diastereoselective cis-hydrogenation of multi-substituted pyridines and arenes is reported. Applying a novel heterogeneous ruthenium catalyst, the corresponding piperidines and cyclohexanes are obtained in high yields (typically >80%) with a good functional group tolerance under mild conditions. The robust ruthenium supported catalyst is smoothly prepared and can be reused multiple times without activity loss.

Manganese-Catalysed Deuterium Labelling of Anilines and Electron-Rich (Hetero)Arenes.

There is a constant need for deuterium-labelled products for multiple applications in life sciences and beyond. Here, a new class of heterogeneous catalysts is reported for practical deuterium incorporation in anilines, phenols, and heterocyclic substrates. The optimal material can be conveniently synthesised and allows for high deuterium incorporation using deuterium oxide as isotope source. This new catalyst has been fully characterised and successfully applied to the labelling of natural products as well as marketed drugs.

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules.

Organic compounds labeled with hydrogen isotopes play a crucial role in numerous areas, from materials science to medicinal chemistry. Indeed, while the replacement of hydrogen by deuterium gives rise to improved absorption, distribution, metabolism, and excretion (ADME) properties in drugs and enables the preparation of internal standards for analytical mass spectrometry, the use of tritium-labeled compounds is a key technique all along drug discovery and development in the pharmaceutical industry. For these reasons, the interest in new methodologies for the isotopic enrichment of organic molecules and the extent of their applications are equally rising. In this regard, this Review intends to comprehensively discuss the new developments in this area over the last years (2017-2021). Notably, besides the fundamental hydrogen isotope exchange (HIE) reactions and the use of isotopically labeled analogues of common organic reagents, a plethora of reductive and dehalogenative deuteration techniques and other transformations with isotope incorporation are emerging and are now part of the labeling toolkit.

A Convenient and Stable Heterogeneous Nickel Catalyst for Hydrodehalogenation of Aryl Halides Using Molecular Hydrogen.

Invited for this month's cover is the group of Matthias Beller at the Leibniz Institute for Catalysis in Rostock in collaboration with Muhammad Anwar and Sarim Dastgir at the Qatar Environment and Energy Research Institute in Doha. The image illustrates a hydrodehalogenation of polybrominated diphenyl ether (PBDE) using a heterogeneous nickel catalyst supported on titanium oxide and dihydrogen. The Research Article itself is available at 10.1002/cssc.202102315.

Scalable and selective deuteration of (hetero)arenes.

Isotope labelling, particularly deuteration, is an important tool for the development of new drugs, specifically for identification and quantification of metabolites. For this purpose, many efficient methodologies have been developed that allow for the small-scale synthesis of selectively deuterated compounds. Due to the development of deuterated compounds as active drug ingredients, there is a growing interest in scalable methods for deuteration. The development of methodologies for large-scale deuterium labelling in industrial settings requires technologies that are reliable, robust and scalable. Here we show that a nanostructured iron catalyst, prepared by combining cellulose with abundant iron salts, permits the selective deuteration of (hetero)arenes including anilines, phenols, indoles and other heterocycles, using inexpensive D2O under hydrogen pressure. This methodology represents an easily scalable deuteration (demonstrated by the synthesis of deuterium-containing products on the kilogram scale) and the air- and water-stable catalyst enables efficient labelling in a straightforward manner with high quality control.

Cobalt-Catalysed Reductive Etherification Using Phosphine Oxide Promoters under Hydroformylation Conditions.

A phosphine-oxide-promoted, cobalt-catalysed reductive etherification using syngas as a reductant is reported. This novel methodology was successfully used to prepare a broad range of unsymmetrical ethers from various aldehydes and alcohols containing diverse functional groups, and was scaled-up to multigram scale under comparably mild conditions. Mechanistic experiments support an acetalization-hydrogenation sequence.

A Convenient and Stable Heterogeneous Nickel Catalyst for Hydrodehalogenation of Aryl Halides Using Molecular Hydrogen.

Hydrodehalogenation is an effective strategy for transforming persistent and potentially toxic organohalides into their more benign congeners. Common methods utilize Pd/C or Raney-nickel as catalysts, which are either expensive or have safety concerns. In this study, a nickel-based catalyst supported on titania (Ni-phen@TiO2 -800) is used as a safe alternative to pyrophoric Raney-nickel. The catalyst is prepared in a straightforward fashion by deposition of nickel(II)/1,10-phenanthroline on titania, followed by pyrolysis. The catalytic material, which was characterized by SEM, TEM, XRD, and XPS, consists of nickel nanoparticles covered with N-doped carbon layers. By using design of experiments (DoE), this nanostructured catalyst is found to be proficient for the facile and selective hydrodehalogenation of a diverse range of substrates bearing C-I, C-Br, or C-Cl bonds (>30 examples). The practicality of this catalyst system is demonstrated by the dehalogenation of environmentally hazardous and polyhalogenated substrates atrazine, tetrabromobisphenol A, tetrachlorobenzene, and a polybrominated diphenyl ether (PBDE).

Copper-catalysed low-temperature water-gas shift reaction for selective deuteration of aryl halides.

The introduction of deuterium atoms into organic compounds is of importance for basic chemistry, material sciences, and the development of drugs in the pharmaceutical industry, specifically for identification and quantification of metabolites. Hence, methodologies for the synthesis of selectively labelled compounds continue to be a major area of interest for many scientists. Herein, we present a practical and stable heterogeneous copper catalyst, which permits for dehalogenative deuteration via water-gas shift reaction at comparably low temperature. This novel approach allows deuteration of diverse (hetero)aryl halides with good functional group tolerance, and no reduction of the aromatic rings or other easily reducible formyl and cyano groups. Multi-gram experiments show the potential of this method in organic synthesis and medicinal chemistry.

HCOOH disproportionation to MeOH promoted by molybdenum PNP complexes.

Molybdenum(0) complexes with aliphatic aminophosphine pincer ligands have been prepared which are competent for the disproportionation of formic acid, thus representing the first example so far reported of non-noble metal species to catalytically promote such transformation. In general, formic acid disproportionation allows for an alternative access to methyl formate and methanol from renewable resources. MeOH selectivity up to 30% with a TON of 57 could be achieved while operating at atmospheric pressure. Selectivity (37%) and catalyst performance (TON = 69) could be further enhanced when the reaction was performed under hydrogen pressure (60 bars). A plausible mechanism based on experimental evidence is proposed.

Catalytic Formal Hydroamination of Allylic Alcohols Using Manganese PNP-Pincer Complexes.

Several manganese-PNP pincer catalysts for the formal hydroamination of allylic alcohols are presented. The resulting γ-amino alcohols are selectively obtained in high yields applying Mn-1 in a tandem process under mild conditions.

Correction: HCOOH disproportionation to MeOH promoted by molybdenum PNP complexes.

[This corrects the article DOI: 10.1039/D1SC04181A.].