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.

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.

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.

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.

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.

Streamlined Synthesis of Diaminopyridines by Pd-Catalyzed Ammonia Coupling with Deactivated Amino-Chloropyridines.

An efficient and cost-effective two-step synthesis of diaminopyridines, fundamental building blocks of biologically active compounds, is reported. The advantages over previously reported routes include cost and wider availability of the bromo-chloropyridine starting materials and the straightforward accessibility to an extended array of diaminopyridine regioisomers. The key enabler of this synthetic strategy is the development of an unprecedented palladium-catalyzed coupling reaction of ammonia with chloropyridines deactivated by the presence of an alkylamino substituent. The coupling reaction was accomplished with very low catalyst loadings under remarkably mild reaction conditions, making the system particularly suitable for both academic and industrial applications. The utility of this methodology is exemplified by the application to the synthesis of highly relevant scaffolds, including the synthetic intermediates of the marketed drugs Ribociclib and Palbociclib.