Acceptorless Dehydrogenation Research Articles

Ruthenium-Catalyzed Synthesis of 2-Pyrazolines via Acceptorless Dehydrogenative Coupling of Allylic Alcohols with Hydrazines.

Described herein is the synthesis of 2-pyrazolines via acceptorless dehydrogenative coupling of allylic alcohols with hydrazines based on a Ru3(CO)12/NHC-phosphine-phosphine ligand L catalytic system. The reaction not only exhibits low catalyst loading (only 0.3 mol %), wide substrate scope, good to excellent yields, and high selectivity but also omits the use of sacrificial hydrogen acceptor with only H2 and H2O as byproducts, making the reaction green and atom-economical.

Acceptorless dehydrogenation of glycerol catalysed by Ir(III) complexes with carbohydrate‐functionalised ligands: a sweet pathway to produce hydrogen and lactic acid

Glycerol, a by‐product of biodiesel production, has gained prominence as a precious platform chemical. To enhance the economic viability of the biodiesel production process and address the surplus of glycerol production, it is essential to transform it into value‐added products. In this context, homogeneous catalysis offers a promising avenue for glycerol valorisation. In this study, we introduce a family of iridium complexes bearing picolineamidate ligands with glucose‐functionalised substituents as novel homogeneous catalysts for glycerol to hydrogen and lactic acid conversion. These complexes exhibit high activity (conversion up to 53.3%) and 99% selectivity after 24 hours of reaction (TOFMAX=159 h‐1, TON24h=2498). Notably, the reaction occurs under ambient air and at milder temperature conditions (120°C) compared to other catalysts. These efforts in glycerol valorisation contribute to reducing biodiesel production costs, increasing the competitiveness of biofuels against petroleum‐based liquid fuels, giving rise to H2, through a global process with negative carbon dioxide emission, and lactic acid utilizable, among other, as a monomer for the synthesis of biodegradable plastics.

Well Defined Phosphine Free Ni-Catalyzed Dehydrogenation of Secondary Alcohols for the Synthesis of Ketones and Ketazines.

In this work, we unveil a novel synthesis of bench stable Ni (II) complexes supported by tetradentate Schiff-base ligands and the complexes were devoid of any phosphine or phosphine-based ligand. These Ni-complexes were successfully applied for the dehydrogenation of secondary alcohols for ketone and ketazine syntheses. Secondary alcohols with different functional groups were well tolerated during catalytic cycle. Moreover, we successfully extended this protocol for the synthesis of biologically significant ketones and ketazines. On the basis of various control experiments, probable reaction pathway was proposed and an acceptorless alcohol dehydrogenation mechanism was suggested.

Acceptorless Dehydrogenation of Alcohols and Polyols Over Cu‐Based Catalysts Prepared by NaBH4 Reduction

AbstractFor the first time, oxide (TiO2, CeO2, ZnO, Al2O3) supported Cu catalysts, prepared by the aqueous reduction method using sodium borohydride, were employed for the acceptorless dehydrogenation of 2‐octanol and various C4–C8 polyols. The method used to prepare the catalysts enabled the formation of small Cu particles in the range of 14–36 nm, depending on the point of the zero charge of the support. We showed that the conversion increased with Cu surface area, where Cu/TiO2 led to the highest conversion of 2‐octanol (>99.9%). The selectivity depends on the support and conversion. Up to 80% conversion, the selectivity to 2‐octanone was between 83% and 90% when using Cu/TiO2. In this study, we also report for the first time the acceptorless dehydrogenation of 1,3‐butanediol, 2,3‐butanediol, 1,2‐pentanediol, and 1,5‐pentanediol in liquid phase. While metal active sites promoted the dehydrogenation reaction, the presence of acidic and basic sites favored the formation of by‐products, mainly resulting from dehydration reactions, pinacol rearrangements, and aldol and retro‐aldol condensations. In addition to value‐added chemicals, all the reactions also released molecular hydrogen.

Recent Advances in Heterogeneously Catalyzed Acceptorless Dehydrogenation of Alcohols to Carbonyl Derivatives and N-heterocyclic Compounds

: Oxidation of alcohols in an oxidant-free condition, commonly known as the acceptorless dehydrogenation (AD) reaction, has recently emerged as one of the widely used processes in synthetic organic chemistry. Alcohol acts as an excellent chemical precursor that produces a variety of dehydrogenated value-added products such as carbonyls, acids, acetals, and several coupling products, followed by the concomitant evolution of molecular hydrogen gas. AD reaction of alcohol, therefore, can be considered as a vital reaction for the hydrogen economy using alcohols as a liquid hydrogen carrier. Over the past decade, the growing importance of AD reactions has set the way for the continuous development of various homogeneous and heterogeneous catalytic systems. With the advantage of reusability and recyclability, heterogeneous catalysts have now become more promising and significant in the catalytic domain. This review aims to make an overview of the transition metal-based heterogeneous catalytic system of acceptorless alcohol dehydrogenation reaction reported till December, 2023.

Cobalt Nanoparticles Catalyzed N-Heterocycles Synthesis via Acceptorless Dehydrogenative Coupling.

The acceptorless dehydrogenation reaction is a sustainable and atom-economical methodology in organic synthesis, resulting in the byproducts of only hydrogen or water. Herein, a robust Co-Si/CN catalyst (derived from ZIF@SiO2 composite) has been synthesized through a one-step assembly process via pyrolysis and etching. This catalyst has been employed for the acceptorless dehydrogenative coupling of 2-aminoalcohols with secondary alcohols, enabling efficient conversion of various substrates into desired quinoline or pyridine derivatives with a yield of up to 94 %.

Acceptorless Dehydrogenation under Neat Reaction Conditions: Synthesis of 2-Aryl/Alkyl Quinazolinones Using Supported Ni NPs as Catalyst

AbstractWe report here a Ni-NPs-catalyzed one-pot synthesis of 2-alkyl/aryl quinazolinone motifs via acceptorless dehydrogenation of alcohol, condensation of an aldehyde intermediate with 2-aminobenzamide, followed by a second dehydrogenation of the cyclized intermediate. The protocol is atom-economical and require earth-abundant Ni as the catalyst. The present report involves the annulation of 2-aminobenzamide with various types of primary alcohols, including aryl/heteroaryl methanol, and aliphatic alcohols, and produces high yields of the desired products under neat conditions. The catalyst was synthesized via a high-temperature pyrolysis strategy, using ZIF-8 as the sacrificial template. The Ni NPs@N-C catalyst was characterized by XPS, HR-TEM, HAADF-STEM, XRD, and ICP-MS. The catalyst is stable even in air at room temperature and displayed excellent activity in the acceptorless dehydrogenative coupling synthesis of quinazolinones and could be recycled five times without appreciable loss of its activity.

Synthesis of non-canonical amino acids through dehydrogenative tailoring.

Amino acids are essential building blocks in biology and chemistry. Whereas nature relies on a small number of amino acid structures, chemists desire access to a vast range of structurally diverse analogues1-3. The selective modification of amino acid side-chain residues represents an efficient strategy to access non-canonical derivatives of value in chemistry and biology. While semisynthetic methods leveraging the functional groups found in polar and aromatic amino acids have been extensively explored, highly selective and general approaches to transform unactivated C-H bonds in aliphatic amino acids remain less developed4,5. Here we disclose a stepwise dehydrogenative method to convert aliphatic amino acids into structurally diverse analogues. The key to the success of this approach lies in the development of a selective catalytic acceptorless dehydrogenation method driven by photochemical irradiation, which provides access to terminal alkene intermediates for downstream functionalization. Overall, this strategy enables the rapid synthesis of new amino acid building blocks and suggests possibilities for the late-stage modification of more complex oligopeptides.

Pincer manganese-catalyzed C–H phosphinomethylation of indoles and naphthols with methanol as C1 block

We here report a facile manganese-catalyzed three-component phosphinomethylation of indoles and naphthols using methanol as a sustainable C1 source and an acceptorless dehydrogenation strategy. A set of indoles, naphthols, and phosphines with different substituents could efficiently undergo the acceptorless dehydrogenative cross-coupling and furnish the corresponding C–H phosphinomethylated indoles and naphthols in moderate to good yields. Mechanistic studies indicate that this transformation proceeds with the dehydrogenation of methanol to form a formaldehyde-coordinated manganese species as the key intermediate.

Photomediated One-Pot Three-Component Approach Enables the Formal Direct N-Acylation/Sulfonylation and α-C-H Functionalization of 1,2,3,4-Tetrahydroisoquinoline.

N-Acyl/sulfonyl-α-functionalized 1,2,3,4-tetrahydroisoquinolines (THIQs) are significant structural motifs in organic synthesis and drug discovery. However, the one-pot approach enabling direct difunctionalization of THIQs remains challenging. Herein we report a photomediated one-pot three-component strategy to access N-acyl/sulfonyl-α-functionalized THIQs. This method features the use of oxygen (from air) as the green oxidant, high atom and step economy, and decent structural diversity. The synthetic applicability of the method was further demonstrated via the facile construction of valuable bioactive molecules. Mechanistic studies indicated that oxidation with singlet oxygen and the acceptor-less dehydrogenation were involved in the photoredox process.

One-Pot Sustainable Synthesis of Highly Substituted Pyrimidines via Acceptorless Dehydrogenative Annulation of Alcohols Using Pincer Ni(II)-NNS Catalysts.

We report an efficient and sustainable synthesis of highly substituted pyrimidines promoted by nickel(II)-NNS pincer-type complexes via acceptorless dehydrogenative annulations of readily available alcohols, malononitrile, and guanidine/benzamidine salt under eco-friendly conditions for the first time. Different sets of Ni(II) complexes (C1-C3) encapsulated in NNS pincer-type thiosemicarbazone ligands have been synthesized and authenticated by analytical and spectroscopic (Fourier transform infrared, nuclear magnetic resonance, and high-resolution mass spectrometry) techniques. The solid state three-dimensional structure of a representative complex (C2) has been determined with the aid of single crystal XRD analysis and confirms a square planar architecture around the nickel ion. Further, the well-defined Ni(II) complexes have been employed as efficient catalysts for the fabrication of a wide range of 4-aminopyrimidine-5-carbonitrile derivatives (33 examples) from readily available alcohols with suitable coupling partners such as malononitrile and guanidine/benzamidine under eco-friendly conditions. The current catalytic approach affords maximum yields up to 95% utilizing 3 mol % catalyst loading and water/hydrogen as the only byproduct. A feasible catalytic pathway has been proposed based on the different control experiment reactions, which clearly indicate that the coupling reaction proceeds via aldehyde and benzylidenemalononitrile intermediates. The practicability of the current protocol has been demonstrated by the large-scale synthesis of one of the products, 4-amino-2,6-diphenylpyrimidine-5-carbonitrile, and a short synthesis of a cytosine antifungal analogue.

Base‐Catalyzed Domino Isomerization/Oxidant‐Free Dehydrogenative Annulation of Allylic Alcohols: Scope, Mechanism, and Application

AbstractA domino reaction comprising four consecutive steps based on the strategy of isomerization of allylic alcohols was developed. This base‐catalyzed protocol provided an approach for constructing polysubstituted quinolines without additional additives. A wide range of di‐ or trisubstituted γ‐aminoaryl allylic alcohols bearing alkyl or (hetero)aryl substituents were transformed to a range of structurally diverse quinolines. The utility of this transformation was demonstrated by the application in the concise synthesis of several polysubstituted quinoline derivatives, including natural products and pharmacological agents. Preliminary mechanistic experiments suggest that the isomerization of γ‐aminoaryl allylic alcohol proceeds via an intramolecular 1,3‐hydrogen shift whereas for the aromatization of the dihydroquinoline intermediate two possible pathways exist: acceptorless dehydrogenation and transfer hydrogenation.

One‐Pot Catalytic Cascade for the Depolymerization of the Lignin β‐O‐4 Motif to Non‐phenolic Dealkylated Aromatics

Aromatic monomers obtained by selective depolymerization of the lignin β‐O‐4 motif are typically phenolic and contain (oxygenated) alkyl substitutions. This work reveals the potential of a one‐pot catalytic lignin β‐O‐4 depolymerization cascade strategy that yields a uniform set of methoxylated aromatics without alkyl side‐chains. This cascade consists of selective acceptorless dehydrogenation of the γ‐hydroxy group, subsequent retro‐aldol reaction cleaving the Cα–Cβ bond followed by in situ acceptorless decarbonylation of the formed aldehydes. This three‐step cascade reaction, catalyzed by an iridium(I)‐BINAP complex, resulted in 75% 1,2‐dimethoxybenzene from G‐type lignin dimers alongside syngas (CO:H2 ≈ 1.4:1). Applying this method to a synthetic G‐type polymer, 11 wt% 1,2‐dimethoxybenzene was obtained. This versatile compound can be easily transformed into 3,4‐dimethoxyphenol, a valuable precursor for pharmaceutical synthesis, through enzymatic catalytic approach. Moreover, the hydrodeoxygenation potential of 1,2‐dimethoxybenzene offers a pathway to produce valuable cyclohexane or benzene derivatives, presenting enticing opportunities for sustainable chemical transformations without the necessity for phenolic mixture upgrading via dealkylation.

One-Pot Catalytic Cascade for the Depolymerization of the Lignin β-O-4 Motif to Non-phenolic Dealkylated Aromatics.

Aromatic monomers obtained by selective depolymerization of the lignin β-O-4 motif are typically phenolic and contain (oxygenated) alkyl substitutions. This work reveals the potential of a one-pot catalytic lignin β-O-4 depolymerization cascade strategy that yields a uniform set of methoxylated aromatics without alkyl side-chains. This cascade consists of selective acceptorless dehydrogenation of the γ-hydroxy group, subsequent retro-aldol reaction cleaving the Cα-Cβ bond followed by in situ acceptorless decarbonylation of the formed aldehydes. This three-step cascade reaction, catalyzed by an iridium(I)-BINAP complex, resulted in 75% 1,2-dimethoxybenzene from G-type lignin dimers alongside syngas (CO:H2 ≈ 1.4:1). Applying this method to a synthetic G-type polymer, 11 wt% 1,2-dimethoxybenzene was obtained. This versatile compound can be easily transformed into 3,4-dimethoxyphenol, a valuable precursor for pharmaceutical synthesis, through enzymatic catalytic approach. Moreover, the hydrodeoxygenation potential of 1,2-dimethoxybenzene offers a pathway to produce valuable cyclohexane or benzene derivatives, presenting enticing opportunities for sustainable chemical transformations without the necessity for phenolic mixture upgrading via dealkylation.

Copper‐cobalt bimetallic nanoparticles for the acceptorless dehydrogenation of alcohols: a combined experimental and theoretical study.

Bimetallic Cu and Co nanoparticles were prepared using the polyol process. The nature of the polyol was found to be decisive to control the distribution of the two metals within the particles, resulting in either core‐shell or quasi‐alloyed structures, as shown by chemical analysis at the single particle level. The particles can be prepared over the entire composition range with a very good control of the Cu/Co molar ratio. The introduction of Cu in the synthetic system allows decreasing significantly the mean size of the resulting particles. The two sets of particles were used as unsupported catalysts for the solvent‐free acceptorless dehydrogenation of octan‐2‐ol. Very good ketone yields were measured when using the quasi‐alloyed particles while lower activities were obtained with core‐shell structures. The Cu25Co75 quasi‐alloyed catalyst could be recycled at least ten times without a significant loss in catalytic activity and particle‐scale chemical analyses confirmed that the recovered particles are still alloyed with no observed demixing. The catalytic results are discussed in the light of different exposed metal surface areas and possible synergetic effects using theoretical predictions.

Cobalt-catalyzed Synthesis of Alkenes and Vinyl Sulfones via Dehydrogenative Coupling of Alcohols and Sulfones.

A novel protocol to access vinyl sulfones and internal/terminal olefins via cobalt-catalyzed acceptorless dehydrogenation coupling (ADC) has been established. This system enables the divergent synthesis of three kinds of olefin compounds through the coupling of alcohols and sulfones under oxidant-free conditions. The broad applicability of this procedure is demonstrated by over forty olefin products, including pharmaceutical-related compounds and complex substrates, in a one-pot process. Preliminary mechanistic studies were conducted, and a proposed reaction pathway was presented.

Selective Conversion of Glycerol to Lactic Acid in Water via Acceptorless Dehydrogenation Catalyzed by a Water-Soluble Metal-Ligand Bifunctional Iridium Catalyst.

An efficient method for the selective conversion of glycerol, the major byproduct of the biodiesel manufacturing process, to lactic acid in water via acceptorless dehydrogenation has been developed. In the presence of a water-soluble [Cp*Ir(6,6'-(OH)2-2,2'-bpy)(H2O)][OTf]2 (0.1 mol %) and KOH (1.1 equiv), the reaction proceeded at 120 °C for 24 h to afford the desired product in >99% yield with >99% selectivity. It was confirmed that OH functional groups in the ligand were crucial for the activity of the iridium complex. Furthermore, density functional theory calculations and mechanistic experiments were also undertaken.

Dehydrogenation of primary alcohols to carboxylic acids in water catalyzed by PNHN-manganese(I) carbonyl complexes

Three classes of manganese(I) complex cation, [(PNHN)Mn(CO)3]Br (Mn1), [(SNHN)Mn(CO)3]Br (Mn2) and [(NRNHN)Mn(CO)3]Br (Mn3 (NMe), Mn4 (NEt), Mn5 (NiPr)), all incorporating a chelating 5,6,7,8-tetrahydro-8-quinolinamine (NHN) but distinct in their third donor atom, have been assessed as catalysts for the dehydrogenative oxidation of primary alcohols to form their corresponding carboxylic acids. Using water as solvent and NaOH as base, PNHN-containing Mn1 proved the most effective allowing both aromatic and aliphatic alcohols to be converted at 160 °C with excellent functional group tolerance (25 examples disclosed). A possible mechanism for this process, that makes use of an acceptorless dehydrogenation pathway, has been proposed and supported by targeted experimentation. Overall, these catalysts show great promise for applications in atom-economic carboxylic acid synthesis as well as in the development of organic hydride-based hydrogen storage systems.

Photocatalyzed H2-Acceptorless Dehydrogenative Borylation by Using Amine Borane

Photocatalyzed H₂-Acceptorless Dehydrogenative Borylation by Using Amine Borane

Mechanistic understanding of the acceptorless dehydrogenation reaction catalyzed by low valent Co(I) complex

Coordination complexes based on the first-row transition metal play pivotal role in homogenous catalysis. However, the variable oxidation states and complicated electronic configurations of first-row transition metal centers result in the ambiguous mechanism. Herein, focusing on a typical Co(Ⅰ)-PNP pincer catalyst developed by Madsen et al. (Chemcatchem, 11 (2019) 2707–2712.), the diversity of mechanistic scenarios caused by low valent cobalt complex is displayed and the competition of each plausible reaction pathways were investigated based on density functional theory (DFT) calculation. The calculated results suggest that the MLC mechanism mediated by Co(I) center prevails in different stage among all possible reaction pathways. Further analysis using the activation strain model elucidates the dual active sites in MLC mechanism leads to a higher interaction energy compared with the Co(I/III) mechanism, in which the reaction basically occurs on the metal center. However, in the high spin state, the metal and the ligand cooperate to provide more interaction energy in the activation of chemical bonds, thereby reducing the activation energy barrier. These theoretical findings are anticipated to enhance current understanding of homogeneous catalysis based on 3d low valent metal centers.