Ammonia-Borane Dependent Transfer Hydrogenation of Carboxylic Esters to Primary Alcohols.

Here, we present a user-friendly protocol that uses bench-stable NH3·BH3 (AB) as the hydrogen transfer agent for the reduction of both aromatic and aliphatic esters without an external catalyst and base, delivering a structurally diverse array of primary alcohols (80-98% yields). The broad functional-group tolerance (halogen, boronic ester, -NO2, -OH, etc.) under environmentally acceptable conditions implies high practical utility. Further, a tandem catalytic conversion of a plastic waste polyethylene terephthalate (PET) bottle to 1,4-benzenedimethanol including fatty esters into respective fatty alcohols was shown.

Transfer Hydrogenation of N- and O-Containing Heterocycles Including Pyridines with H3N-BH3 Under the Catalysis of the Homogeneous Ruthenium Precatalyst.

In this study, we report a transfer hydrogenation protocol that utilizes borane-ammonia (H3N-BH3) as the hydrogen source and a commercially available RuCl3·xH2O precatalyst for the selective aromatic reduction of quinolines, quinoxalines, pyridines, pyrazines, indoles, benzofurans, and furan derivatives to form the corresponding alicyclic heterocycles in good to excellent isolated yields. Applications of this straightforward protocol include the efficient preparation of useful key pharmaceutical intermediates, such as donepezil and flumequine, including a biologically active compound.

Homogenous nickel-catalyzed chemoselective transfer hydrogenation of functionalized nitroarenes with ammonia-borane.

Homogeneous Ni-catalyzed highly selective transfer hydrogenation of nitroarenes was successfully established using NH3BH3 as a hydrogen source. A broad range of functional groups were selectively reduced to provide the corresponding anilines in good to high yields. Further, pharmaceutically active compounds can be prepared that would otherwise be challenging to access.

Methanol as a Potential Hydrogen Source for Reduction Reactions Enabled by a Commercial Pt/C Catalyst.

Catalytic reduction reactions using methanol as a transfer hydrogenating agent is gaining significant attention because this simple alcohol is inexpensive and produced on a bulk scale. Herein, we report the catalytic utilization of methanol as a hydrogen source for the reduction of different functional organic compounds such as nitroarenes, olefins, and carbonyl compounds. The key to the success of this transformation is the use of a commercially available Pt/C catalyst, which enabled the transfer hydrogenation of a series of simple and functionalized nitroarenes-to-anilines, alkenes-to-alkanes, and aldehydes-to-alcohols using methanol as both the solvent and hydrogen donor. The practicability of this Pt-based protocol is showcased by demonstrating catalyst recycling and reusability as well as reaction upscaling. In addition, the Pt/C catalytic system was also adaptable for the N-methylation and N-alkylation of anilines via the borrowing hydrogen process. This work provides a simple and flexible approach to prepare a variety of value-added products from readily available methanol, Pt/C, and other starting materials.

Challenges and recent advancements in the transformation of CO2 into carboxylic acids: straightforward assembly with homogeneous 3d metals.

The transformation of carbon dioxide (CO2) into useful chemicals, advanced materials, and energy is a long-standing challenge in both fundamental science and industry. In recent years, utilization of CO2 in the presence of inexpensive and non-negligible environmentally friendly 3d metal-based catalysts (Fe, Mn, Co, Ni, Cu and Ti) has become one of the most attractive topics. Particular attention has been given to the synthesis of carboxylic acids and their derivatives since these molecules serve as key intermediates in the chemical, fertilizer, and pharmaceutical sectors. Considering numerous challenges linked with CO2 reactivity, a number of research groups have recently focused on the transformation of CO2 into carboxylic acids by following thermo-, photo-, and electrochemical strategies. However, facile access to such acids remains a vital challenge in catalysis and in organic synthesis owing to the high stability of the CO2 molecule in which the carbon atom has the highest oxidation state. Another hurdle is to solve the selectivity issue caused by the reaction of different catalytic systems with CO2 in the presence of reactive functional group-containing molecules. Despite all these issues, a wide range of transition metal-based catalysts have been applied in this direction, but owing to their cheaper price and inherent reactivity, 3d metals are at the forefront in the CO2 utilization domain. Considering these, we aim to summarise recent advances (over the past five years) of 3d-metal complexes and their reactivity towards the activation of CO2 for the synthesis of carboxylic acids. Furthermore, we discuss current research trends, knowledge gaps, and invigorating perspectives on future advances.

Lignin Residue-Derived Carbon-Supported Nanoscale Iron Catalyst for the Selective Hydrogenation of Nitroarenes and Aromatic Aldehydes.

Heterogeneous iron-based catalysts governing selectivity for the reduction of nitroarenes and aldehydes have received tremendous attention in the arena of catalysis, but relatively less success has been achieved. Herein, we report a green strategy for the facile synthesis of a lignin residue-derived carbon-supported magnetic iron (γ-Fe2O3/LRC-700) nanocatalyst. This active nanocatalyst exhibits excellent activity and selectivity for the hydrogenation of nitroarenes to anilines, including pharmaceuticals (e.g., flutamide and nimesulide). Challenging and reducible functionalities such as halogens (e.g., chloro, iodo, and fluoro) and ketone, ester, and amide groups were tolerated. Moreover, biomass-derived aldehyde (e.g., furfural) and other aromatic aldehydes were also effective for the hydrogenation process, often useful in biomedical sciences and other important areas. Before and after the reaction, the γ-Fe2O3/LRC-700 nanocatalyst was thoroughly characterized by X-ray diffraction (XRD), N2 adsorption-desorption, X-ray photoelectron spectroscopy (XPS), high-resolution transmission electron microscopy (HR-TEM), Raman spectroscopy, and thermogravimetric analysis (TGA). Additionally, the γ-Fe2O3/LRC-700 nanocatalyst is stable and easily separated using an external magnet and recycled up to five cycles with no substantial drop in the activity. Eventually, sustainable and green credentials for the hydrogenation reactions of 4-nitrobenzamide to 4-aminobenzamide and benzaldehyde to benzyl alcohol were assessed with the help of the CHEM21 green metrics toolkit.

Catalytic reductive aminations using molecular hydrogen for synthesis of different kinds of amines.

Reductive aminations constitute an important class of reactions widely applied in research laboratories and industries for the synthesis of amines as well as pharmaceuticals, agrochemicals and biomolecules. In particular, catalytic reductive aminations using molecular hydrogen are highly valued and essential for the cost-effective and sustainable production of different kinds of amines and their functionalization. These reactions couple easily accessible carbonyl compounds (aldehydes or ketones) with ammonia, amines or nitro compounds in the presence of suitable catalysts and hydrogen that enable the preparation of linear and branched primary, secondary and tertiary amines including N-methylamines and molecules used in life science applications. In general, amines represent valuable fine and bulk chemicals, which serve as key precursors and central intermediates for the synthesis of advanced chemicals, life science molecules, dyes and polymers. Noteworthily, amine functionalities are present in a large number of pharmaceuticals, agrochemicals and biomolecules, and play vital roles in the function of these active compounds. In general, reductive aminations are challenging processes, especially for the syntheses of primary amines, which often are non-selective and suffer from over-alkylation and reduction of carbonyl compounds to the corresponding alcohols. Hence, the development of suitable catalysts to perform these reactions in a highly efficient and selective manner is crucial and continues to be important and attracts scientific interest. In this regard, both homogeneous and heterogeneous catalysts have successfully been developed for these reactions to access various amines. There is a need for a comprehensive review on catalytic reductive aminations to discuss the potential catalysts used and applicability of this methodology in the preparation of different kinds of amines, which are of commercial, industrial and medicinal importance. Consequently, in this review we discuss catalytic reductive aminations using molecular hydrogen and their applications in the synthesis of functionalized and structurally diverse benzylic, heterocyclic and aliphatic primary, secondary and tertiary amines as well as N-methylamines and more complex drug targets. In addition, mechanisms of reductive aminations including selective formation of desired amine products as well as possible side reactions are emphasized. This review aims at the scientific communities working in the fields of organic synthesis, catalysis, and medicinal and biological chemistry.

Commercial Pd/C-Catalyzed N-Methylation of Nitroarenes and Amines Using Methanol as Both C1 and H2 Source.

Herein, we report commercially available carbon-supported-palladium (Pd/C)-catalyzed N-methylation of nitroarenes and amines using MeOH as both a C1 and a H2 source. This transformation proceeds with high atom-economy and in an environmentally friendly way via borrowing hydrogen mechanism. A total of >30 structurally diverse N-methylamines, including bioactive compounds, were selectively synthesized with isolated yields of up to 95%. Furthermore, selective N-methylation and deuteration of nimesulide, a nonsteroidal anti-inflammatory drug, were realized through the late-stage functionalization.

Convenient iron-catalyzed reductive aminations without hydrogen for selective synthesis of N-methylamines.

N-Methylated amines play an important role in regulating the biological and pharmaceutical properties of all kinds of life science molecules. In general, this class of compounds is synthesized via reductive amination reactions using high pressure of molecular hydrogen. Thus, on laboratory scale especially in drug discovery, activated (toxic) methyl compounds such as methyl iodide and dimethyl sulfate are still employed, which also generate significant amounts of waste. Therefore, the development of more convenient and operationally simple processes for the synthesis of advanced N-methylamines is highly desired. Herein, we report the synthesis of functionalized and structurally diverse N-methylamines directly from nitroarenes and paraformaldehyde, in which the latter acts as both methylation and reducing agent in the presence of reusable iron oxide catalyst. The general applicability of this protocol is demonstrated by the synthesis of >50 important N-methylamines including highly selective reductive N-methylations of life science molecules and actual drugs, namely hordenine, venlafaxine, imipramine and amitriptyline.

Transition-Metal-Catalyzed Utilization of Methanol as a C1 †Source in Organic Synthesis.

Methanol is used as a common solvent, cost-effective reagent, and sustainable feedstock for value-added chemicals, pharmaceuticals, and materials. Among the various applications, the utilization of methanol as a C1 source for the formation of carbon-carbon, carbon-nitrogen, and carbon-oxygen bonds continues to be important in organic synthesis and drug discovery. In particular, the synthesis of C-, N-, and O-methylated products is of central interest because these motifs are found in a large number of natural products as well as fine and bulk chemicals. In this Minireview, we summarize the utilization of methanol as a C1 source in methylation, methoxylation, formylation, methoxycarbonylation, and oxidative methyl ester formation reactions.

Synthesis of nitriles from amines using nanoscale Co3O4-based catalysts via sustainable aerobic oxidation.

The selective oxidation of amines for the benign synthesis of nitriles under mild conditions is described. Key to success for this transformation is the application of reusable cobalt oxide-based nanocatalysts. The resulting nitriles constitute key precursors and central intermediates in organic synthesis.

Palladium-Catalyzed Trifluoromethylation of (Hetero)Arenes with CF3 Br.

The CF3 group is an omnipresent motif found in many pharmaceuticals, agrochemicals, catalysts, materials, and industrial chemicals. Despite well-established trifluoromethylation methodologies, the straightforward and selective introduction of such groups into (hetero)arenes using available and less expensive sources is still a major challenge. In this regard, the selective synthesis of various trifluoromethyl-substituted (hetero)arenes by palladium-catalyzed C-H functionalization is herein reported. This novel methodology proceeds under comparably mild reaction conditions with good regio- and chemoselectivity. As examples, trifluoromethylations of biologically important molecules, such as melatonin, theophylline, caffeine, and pentoxifylline, are showcased.

Palladium-Catalyzed Carbonylative Cyclization of Arenes by C-H Bond Activation with DMF as the Carbonyl Source.

A novel palladium-catalyzed CO-gas- and autoclave-free protocol for the synthesis of 11H-pyrido[2,1-b]quinazolin-11-ones has been developed. Quinazolinones, which are omnipresent motif in many pharmaceuticals and agrochemicals, were prepared in good yields by C-H bond activation and annulation using DMF as the CO surrogate. A (13) CO-labelled DMF control experiment demonstrated that CO gas was released from the carbonyl of DMF with acid as the promotor. The kinetic isotope effect (KIE) value indicated that the C-H activation step may not be involved in the rate-determining step. This methodology is operationally simple and showed a broad substrate scope with good to excellent yields.

Heterogeneous platinum-catalyzed C-H perfluoroalkylation of arenes and heteroarenes.

Fluorinated organic compounds are gaining increasing interest for life science applications. The replacement of hydrogen in arenes or heteroarenes by a perfluoroalkyl group has a profound influence on the physical and biological properties of such building blocks. Here, an operationally simple protocol for the direct C-H perfluoroalkylation of (hetero)arenes with R(f)I or R(f)Br has been developed, using a robust supported platinum catalyst. The ready availability of the starting materials, the excellent substrate tolerance, and the reusability of the catalyst make this method attractive for the synthesis of a variety of perfluoroalkyl-substituted aromatic compounds. Preliminary mechanistic studies revealed the formation of radicals to be crucial in the reaction system.

Palladium-catalyzed carbonylative reactions of 1-bromo-2-fluorobenzenes with various nucleophiles: effective combination of carbonylation and nucleophilic substitution.

A systematic study on the carbonylative transformation of 1-bromo-2-fluorobenzenes with various nucleophiles has been performed. Different types of double nucleophiles, such as NN, NC, OC, and NS, can be effectively applied as coupling partners. The corresponding six-membered heterocycles were isolated in moderate to good yields.

Palladium-catalyzed carbonylation of 2-bromoanilines with 2-formylbenzoic acid and 2-halobenzaldehydes: efficient synthesis of functionalized isoindolinones.

A concise and highly versatile method for the synthesis of functionalized isoindolinones is reported. Various 2-bromoanilines undergo palladium-catalyzed carbonylation with 2-formylbenzoic acid under a convenient and mild procedure to give good to excellent yields of the corresponding isoindolinones. Additionally, 2-halobenzaldehydes can be applied as substrates in palladium-catalyzed double-carbonylation to provide identical compounds in moderate to good yields.

Palladium-catalyzed carbonylative [3+2+1] annulation of N-aryl-pyridine-2-amines with internal alkynes by C-H activation: facile synthesis of 2-quinolinones.

We describe here a novel procedure for the synthesis of highly substituted 2-quinolinones. By this newly developed approach, 2-quinolinone derivatives were prepared in moderate to good yields by carbonylative cyclization of N-aryl-pyridine-2-amines and internal alkynes by CH activation. Remarkably, [Mo(CO)6 ] was applied as a solid CO source and the reaction proceeded in an atom economic manner.

Palladium-catalyzed carbonylations of aryl bromides using paraformaldehyde: synthesis of aldehydes and esters.

Carbonylation reactions represent useful tools for organic synthesis. However, the necessity to use gaseous carbon monoxide is a disadvantage for most organic chemists. To solve this problem, novel protocols have been developed for conducting palladium-catalyzed reductive carbonylations of aryl bromides and alkoxycarbonylations using paraformaldehyde as an external CO source (CO gas free). Hence, aromatic aldehydes and esters were synthesized in moderate to good yields.

Base-controlled selectivity in the synthesis of linear and angular fused quinazolinones by a palladium-catalyzed carbonylation/nucleophilic aromatic substitution sequence.

A new approach for the facile synthesis of fused quinazolinone scaffolds through a palladium-catalyzed carbonylative coupling followed by an intramolecular nucleophilic aromatic substitution is described. The base serves as the key modulator: Whereas DBU gives rise to the linear isomers, Et3N promotes the preferential formation of angular products. Interestingly, a light-induced 4+4 reaction of the product was also observed.