Acceptorless Dehydrogenation Research Articles

Synthesis of Alkenyl Nitriles by Bidentate Cobalt-Catalyzed Acceptorless Dehydrogenation Coupling of Alcohols and Nitriles

AbstractA bidentate Co(III)-catalyzed α-olefination of nitriles has been developed. This one-pot protocol provides a simple procedure for the synthesis of alkenyl nitriles from diverse alcohols and nitriles. An extensive substrate scope, good functional-group compatibility, and high atom economy are displayed. Preliminary mechanistic studies revealed that C=C bond formation proceeds through activation of the O–H bond of the alcohol via an unsaturated 16-electron intermediate cobalt complex, and subsequent condensation of the in situ-formed aldehyde with the nitrile. Remarkably, this method liberates H2 and H2O as the only byproducts.

Catalytic acceptorless dehydrogenation of alcohols using cobalt(I) pincer complexes supported by a P-GeH-P ligand.

We report a novel P-GeH-P pincer ligand and its cobalt(I) complex, which catalyzes the acceptorless dehydrogenation of alcohols. The Ge-Co complex, featuring a reactive Ge-H bond, shows distinct catalytic properties compared to silicon-based analogues. Moreover, the complex enables the one-pot synthesis of 2-quinolone derivatives, highlighting its potential in organic synthesis.

Synthesis of Pyrimidines and Quinazolines via Acceptorless Dehydrogenative Coupling Catalyzed by PNN‐Pd Complex

AbstractIn this study, we report the catalytic application of PdIIPNN [PNN: 2,6‐{(R2P)N(H)(C5H3N)(C2HN3C6H5)}] (L1 R = Ph; L2 R = tBu) pincer complexes (Pd1–Pd4) for the sustainable and cost‐effective synthesis of pharmacologically important pyrimidines and quinazolines by acceptorless dehydrogenative coupling of alcohols. Among four mixed donor PdII aromatized and dearomatized complexes, [PdCl{RPHNN‐κ3‐P,N,N]Cl and [PdCl{RPNN}‐κ3‐P,N,N] (R = Ph or tBu), tert‐butylphosphinyl complex was found to be more efficient in the catalytic reactions. A wide range of substituted pyrimidine (45 examples) derivatives was synthesized from amidine, benzyl alcohols and ketones using Pd2 (0.1 mol%) in toluene at 110 °C. Further, the catalyst was found to be effective for the synthesis of quinazolines (22 examples) using 2‐aminobenzyl alcohols and benzonitriles. HRMS and NMR studies confirmed reactions proceeding through Pd‐alkoxide and Pd‐hydride intermediates.

One‐Pot Cascade [3 + 2 + 1] Annulation: Synthesis and Mechanistic Insight of s‐Triazines and Pyrimidines Using Azo‐Supported Metalloradical Nickel Catalyst

AbstractHighly efficient Ni‐catalyzed C─N/C─C bond formation from amidines during the [3 + 2 + 1] annulation by primary alcohols alone or by primary alcohols with secondary alcohols/phenyl acetylenes has been successfully accomplished toward scaled synthesis of s‐triazine and pyrimidines, respectively. A strongly π‐acidic bis‐azo NNN‐pincer scaffold was successfully introduced for dual functionalization such as augmenting the sustainability of the molecular catalyst by enhancing the metal–ligand integrity and interposing a potent electron‐sink chromophore. The high yield synthesis (up to 94%) of poly‐azaheterocycles with merely 0.001 mol% catalyst loading demonstrates the potency of azo‐anion radical assisted catalysis. A diverse range of primary and secondary alcohols are successfully used as substrates. Furthermore, use of methanol/ethanol as C1/C2 synthon (alkylating agents) enables the formation of challenging imine intermediates from amidines through dehydrogenation under mild conditions. This facilitates the synthesis of wide varieties of s‐triazines, and pyrimidines driven by the auto‐tandem catalyst. Mechanistic investigations reveal that the formation of C─C and C─N bonds proceed through a metalloradical catalysis (MRC) pathway instead of borrowing hydrogen (BH) method and thereby addresses the challenge of controlling stereoselection. This process is initiated by Ni‐catalyzed acceptorless dehydrogenation (AD) of the alcohol substrate, followed by a series of sequential steps, including condensation, aza‐Michael addition, cyclization, and subsequent dehydrogenation. The well‐defined one‐electron reductive response at −0.34 V (versus Fc+/Fc) is indicative of the involvement of azo anion radical during catalytic annulation. The formation of the ligand radical intermediate was further substantiated by an electron paramagnetic resonance (EPR) study conducted both in the presence and absence of radical scavengers, specifically 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO), and butylated hydroxytoluene (BHT).

Acceptorless oxidant-free dehydrogenation of amines catalyzed by Ru-hydride complexes of amide-acid/ester ligands.

Traditional dehydrogenation of amines involves the transfer of hydrogen molecule(s) from a substrate to an acceptor. In acceptorless dehydrogenation, hydrogen gas is liberated without an oxidant, providing an efficient synthetic method. Acceptorless dehydrogenation of primary amines to nitriles without using an oxidant or hydrogen acceptor is significant yet challenging. Herein, we present efficient Ru-based catalysts capable of carrying out such a transformation with hydrogen gas as the only by-product. A new class of air and moisture-stable ruthenium-hydride complexes (1-4) of amide-acid/ester-based ligands have been synthesized and characterized. Crystal structures of two representative complexes, 2 and 3, illustrate the bidentate N-O coordination mode of the ligands. At the same time, additional binding sites are occupied by one hydride, one CO, and two PPh3 co-ligands. The catalytic behavior of these complexes is explored towards the oxidant-free, acceptorless, and selective dehydrogenation of primary and secondary amines affording nitriles and imines, respectively. Among four Ru(II) complexes, complex 2 showed the best catalytic activity for the dehydrogenation of amines. A wide variety of both primary and secondary amines were utilized to explore the substrate scope. The catalytic system tolerated both electron-withdrawing and electron-releasing substituents on amine substrates. Various control experiments and mechanistic studies were carried out to support the dehydrogenation of amines by using complex 2 as a representative catalyst.

High‐Density Catalytic Sites Grafting on 2D‐Metal Oxides for Acceptorless Alcohol Dehydrogenation

Installing well‐defined high density single‐atomic catalyst (SAC) sites is highly desired for the synergistic cooperative effect in efficient chemical synthesis but elusive to synthesize due to unavoidable atomic segregation into clusters or particulates. We implemented a 2D‐nanoconfined SAC grafting strategy. Inside a bilayer silica envelope, single metal hydroxide layer, pre‐loaded with the catalytic metal (Pt, Pd, Ir) precursors, underwent controlled thermal conversion to the homogeneously embedded SACs decorated onto the in‐situ generated 1 nm‐thin transition metal oxide (TMO) nanosheet. Ultranarrow confined slit‐space exclusively availed laterally emerging cation vacancies of TMO host, as atomic scale sockets to capture SACs within 2D‐plane while vertically restricting the atomic aggregation into nanoparticulates. High density SACs stably decorated on isolated TMO nanosheet, could be obtained in a controllable manner. Well‐defined SACs on TMO were conveniently employed for acceptorless dehydrogenation of a variety of alcohols with quite high activities outperforming reported catalysts. In‐depth, mechanistic investigation revealed the dramatic enhancement in acceptorless dehydrogenation reaction rates by following distinct reaction pathways (concerted or stepwise) depending on the density of SACs cooperativity effect. Such advantageous effect is distinct from the reactions on isolated metal sites in low‐density SACs or nanoparticle surface.

High-Density Catalytic Sites Grafting on 2D-Metal Oxides for Acceptorless Alcohol Dehydrogenation.

Installing well-defined high density single-atomic catalyst (SAC) sites is highly desired for the synergistic cooperative effect in efficient chemical synthesis but elusive to synthesize due to unavoidable atomic segregation into clusters or particulates. We implemented a 2D-nanoconfined SAC grafting strategy. Inside a bilayer silica envelope, single metal hydroxide layer, pre-loaded with the catalytic metal (Pt, Pd, Ir) precursors, underwent controlled thermal conversion to the homogeneously embedded SACs decorated onto the in-situ generated 1 nm-thin transition metal oxide (TMO) nanosheet. Ultranarrow confined slit-space exclusively availed laterally emerging cation vacancies of TMO host, as atomic scale sockets to capture SACs within 2D-plane while vertically restricting the atomic aggregation into nanoparticulates. High density SACs stably decorated on isolated TMO nanosheet, could be obtained in a controllable manner. Well-defined SACs on TMO were conveniently employed for acceptorless dehydrogenation of a variety of alcohols with quite high activities outperforming reported catalysts. In-depth, mechanistic investigation revealed the dramatic enhancement in acceptorless dehydrogenation reaction rates by following distinct reaction pathways (concerted or stepwise) depending on the density of SACs cooperativity effect. Such advantageous effect is distinct from the reactions on isolated metal sites in low-density SACs or nanoparticle surface.

Robust tetrazole-linked bimetallic Ru(II) complexes as catalysts for base-free acceptor-less double dehydrogenation of primary amines to nitriles under milder conditions

Robust tetrazole-linked bimetallic Ru(II) complexes as catalysts for base-free acceptor-less double dehydrogenation of primary amines to nitriles under milder conditions

Sustainable Synthesis of Substituted 1,3,5-Triazines by [ONO]-Pincer-Supported Nickel(II) Complexes via an Acceptorless Dehydrogenative Coupling Strategy.

A facile, cost-effective, and sustainable synthesis of substituted triazines from primary alcohols by newly synthesized nickel pincer-type complexes (1-3) has been described. Herein, we report the synthesis of a set of three well-defined Ni(II) O^N^O pincer-type complexes, structurally characterized by analytical, spectral, and X-ray diffraction techniques. Further, the nickel complexes are explored as efficient catalysts (4 mol %) for the construction of 2,4,6-substituted 1,3,5-triazines from readily available alcohols via an acceptorless dehydrogenative coupling (ADC) strategy. A wide range of substituted triazine derivatives (33 examples) has been synthesized from the coupling of alcohols and benzamidine/guanidine hydrochloride with a maximum isolated yield of 92% under mild conditions, with eco-friendly H2O and H2 gas as the only byproducts. A plausible mechanism has been proposed based on a sequence of control experiments. Interestingly, the short synthesis of the antiulcer drug irsogladine and the large-scale synthesis of 2,4-diphenyl-6-(p-tolyl)-1,3,5-triazine highlight the convenience of the current methodology.

Catalytic acceptorless complete dehydrogenation of cycloalkanes

The advancement of an effective hydrogen liberation technology from liquid organic hydrogen carriers, particularly cycloalkanes such as cyclohexane and methylcyclohexane, holds significance in realizing a hydrogen-centric society. However, the attainment of homogeneous catalytic acceptorless dehydrogenation characterized by elevated selectivity for thorough aromatization under mild conditions remains unrealized. In this study, a catalyst system, facilitated by a double hydrogen atom transfer processes, has been devised for the catalytic acceptorless dehydrogenation of inert cycloalkanes at ambient temperature under visible light irradiation. Through the synergistic utilization of tetrabutylammonium chloride and thiophosphoric acid hydrogen atom transfer catalysts, successful catalytic acceptorless dehydrogenation with comprehensive aromatization has been accomplished with potential liquid organic hydrogen carrier candidates and showcased high functional group tolerance.

Unveiling a unique outer-sphere pathway in manganese-catalyzed acceptorless dehydrogenation reaction.

First-row transition metals are widely used in acceptorless dehydrogenative coupling reactions, making the detailed investigation of their catalytic mechanisms crucial for the rational design of efficient catalysts. In this study, density functional theory (DFT) was employed to explore the mechanism of an acceptorless dehydrogenation reaction catalyzed by a bifunctional complex based on a high-spin Mn(II) center. The computational results reveal that the Mn(II) catalyst follows a novel dehydrogenation pathway, where the external base KOH first coordinates to the metal center, and dehydrogenation proceeds via an outer-sphere mechanism. The hydride transfer step is identified as the rate-determining step, with an energy barrier of 26.3 kcal mol-1, consistent with experimental results. To further investigate the selectivity of the mechanism, energy decomposition analysis (EDA) and extended transition state-natural orbitals for chemical valence (ETS-NOCV) analysis were conducted on key transition states. The results show that the small steric hindrance and strong orbital interactions of the external base KOH are the key factors contributing to the selectivity of this mechanism. These findings not only deepen our understanding of the reaction mechanism but also provide valuable theoretical insights for the design and optimization of future acceptorless dehydrogenation catalysts.

Chromium catalyzed acceptorless dehydrogenative (cross)coupling of primary amines to secondary imines.

We present here acceptorless dehydrogenative coupling of primary amines to form secondary aldimines catalyzed by a complex of Earth-abundant chromium. The reaction is promoted by Cr(DAFO)(CO)4 (DAFO = 4,5-diazafluorene-9-one) without using any additives, base or oxidant generating NH3 and H2 as sole by-products. Dehydrogenative cross-coupling of primary amines with aniline derivatives to unsymmetrical secondary imines was also achieved with good to excellent yields. A probable mechanism is proposed based on the stoichiometric investigation and computational studies.

Ruthenium-Hydride Complexes Facilitated Sustainable Synthesis of Isoxazolones via Acceptorless Dehydrogenative Annulation of Alcohols.

A streamlined strategy for the one-pot synthesis of isoxazolone analogues has been developed through an acceptorless dehydrogenative annulation (ADA) pathway by employing new Ru(II) hydride complexes as effective catalysts. New Ru(II) complexes (C1-C3) tailored with N̂O chelating carbazolone benzhydrazone ligands were synthesized and their formation was confirmed using analytical and spectral techniques including FT-IR and NMR. The structural configuration of the complexes featuring an octahedral geometry around the Ru(II) ion was precisely determined by single-crystal X-ray diffraction analysis. Further, the catalytic efficacy of the titled complexes has been established for the facile and productive synthesis of isoxazolone derivatives from a diverse range of benzyl alcohols, methyl acetoacetate/ethyl benzoylacetate and hydroxylamine hydrochloride, generating excellent yields of up to 93% under well-suited mild conditions with 1 mol % of catalyst loading. A sequence of time-dependent control experiments unveiled the ADA route, indicating the initial generation of an 4-methoxy benzaldehyde intermediate followed by 3-phenylisoxazol-5(4H)-one, accompanied by the release of water and hydrogen as byproducts. Gram-scale synthesis of the compound indicates the industrial relevance of our synthetic strategy. A short synthesis of medicinally active androgen antagonist illustrates the utility of the present protocol.

An NNN Pd(II) pincer complex with 1,1-diaminoazine: a versatile catalyst for acceptorless dehydrogenative coupling reactions.

An azine-based, non-palindromic, neutral NNN-pincer ligand was synthesised in a single step with an yield of 85%. The palladation of the ligand, using Pd(OAc)2, was performed in acetonitrile at room temperature to obtain the pincer complex in 88% yield through a simple, cost-effective, and straightforward synthetic procedure. The structure of the complex was confirmed by 1H NMR, 13C NMR, FT-IR, and mass spectrometry. The variable temperature NMR spectra revealed the stability of the complex even at higher temperatures, a characteristic feature of pincer complexes. The generated complex proved to be a versatile catalyst for Acceptorless Dehydrogenative Coupling (ADC) to synthesize N-heterocycles: (i) 1,2-disubstituted benzimidazoles, (ii) 2-phenylquinolines, (iii) 2-phenylquinoxalines and (iv) 2-phenylquinazolinones. Since the side products of the reactions are H2O and H2 gas, the catalysis can be considered as a green catalytic process. Quantum chemical calculations indicated the participation of a possible nitrene-imide conversion process during the Metal-Ligand Cooperation (MLC) in ADC reactions.

Photocatalytic acceptorless dehydrogenation of flavanones by cationic Eosin Y as a bifunctional catalyst.

We report the first example of photocatalytic acceptorless dehydrogenation using cationic Eosin Y as a bifunctional photocatalyst, without metal catalysts or HAT reagents. Under Bayesian optimized conditions, a wide range of flavones were synthesized in moderate to excellent yields, many of which were reported with biological activities. Mechanistic studies suggest that flavones likely form through two HAT processes, with hydrogen release occurring via photoredox.

Sustainable Hydrogen Production by Glycerol and Monosaccharides Catalytic Acceptorless Dehydrogenation (AD) in Homogeneous Phase.

In the quest for sustainable hydrogen production, the use of biomass-derived feedstock is gaining importance. Acceptorless Dehydrogenation (AD) in the presence of efficient and selective catalysts has been explored worldwide as a suitable method to produce hydrogen from hydrogen-rich simple organic molecules. Among these, glycerol and sugars have the advantage of being inexpensive, abundant, and obtainable from fatty acid basic hydrolysis (biodiesel industry) and from biomass by biochemical and thermochemical processing, respectively. Although heterogeneous catalysts are more widely used for hydrogen production from biomass-based feedstock, the harsh reaction conditions often limit their applicability due to the deactivation of active sites caused by the coking of carbonaceous materials. Moreover, heterogeneous catalysts are more difficult to fine-tune than homogeneous counterparts, and the latter also allow for high process selectivities under milder conditions. The present Concept article summarizes the main features of the most active homogeneous catalysts reported for glycerol and monosaccharides AD. In order to directly compare hydrogen production efficiencies, the choice of literature works was limited to reports where hydrogen was clearly quantified by yields and turnover numbers (TONs). The types of transition metals and ligands are discussed, together with a perspective view on future challenges of homogeneous AD reactions for practical applications.

Cu-UiO-66 Catalyzed Synthesis of Imines via Acceptorless Dehydrogenative Coupling of Alcohols and Amines.

Herein, the Cu-UiO-66 catalyst was developed for acceptorless dehydrogenative coupling (ADC) between alcohols and amines to produce imines. The Cu-UiO-66 catalyst was synthesized by installing Cu2+ onto Zr-oxo clusters in UiO-66, and the catalyst efficiently catalyzes the ADC reaction under mild and environmentally friendly conditions with excellent selectivity. Mechanistic studies reveal that the O2⋅- radicals and porosity of formed in Cu-UiO-66 participate cooperatively during the catalytic cycle. Meanwhile, the only by-product of the system is environmentally benign water. Cycling tests and hot filtration tests showed that the Cu-UiO-66 catalyst exhibited excellent stability and catalytic activity during the reaction. Importantly, the Cu-UiO-66 catalyst might provide a promising strategy for the ADC reaction between alcohols and amines to produce imines.

A Protocol for Unveiling the Nature of Photocatalytic Hydrogen Evolution Reactions: True Water Splitting or Sacrificial Reagent Acceptorless Dehydrogenation?

AbstractPhotocatalytic water splitting for hydrogen evolution is a highly topical subject in academic research and a promising approach for sustainable fuel production from solar energy. Due to the mismatched energy diagram of the photosensitizer (especially semiconductor‐based materials where band‐edge engineering is not trivial) and the redox potential of the half‐reactions of water splitting, photocatalytic H2 generation from water splitting is usually accelerated by the addition of hole scavengers, i.e. sacrificial reagents such as alcohols, amines, and thiols. However, the source of the protons of the evolved H2 is often neglected, and it is questionable whether such systems are really water splitting. Here, we discuss recent reports on sacrificial reagent‐assisted photocatalytic water splitting and present our recent findings, which showcase that the sacrificial reagent in the investigated photocatalytic water splitting systems inherently undergoes acceptorless dehydrogenation, with H2O serving as the proton shuttle, the amount of which doesn't change during the course of the reaction.

A Protocol for Unveiling the Nature of Photocatalytic Hydrogen Evolution Reactions: True Water Splitting or Sacrificial Reagent Acceptorless Dehydrogenation?

Photocatalytic water splitting for hydrogen evolution is a highly topical subject in academic research and a promising approach for sustainable fuel production from solar energy. Due to the mismatched energy diagram of the photosensitizer (especially semiconductor-based materials where band-edge engineering is not trivial) and the redox potential of the half-reactions of water splitting, photocatalytic H2 generation from water splitting is usually accelerated by the addition of hole scavengers, i.e. sacrificial reagents such as alcohols, amines, and thiols. However, the source of the protons of the evolved H2 is often neglected, and it is questionable whether such systems are really water splitting. Here, we discuss recent reports on sacrificial reagent-assisted photocatalytic water splitting and present our recent findings, which showcase that the sacrificial reagent in the investigated photocatalytic water splitting systems inherently undergoes acceptorless dehydrogenation, with H2O serving as the proton shuttle, the amount of which doesn't change during the course of the reaction.

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.