Dehydrogenative Coupling Of Primary Alcohols Research Articles

Nickel Pincer Complexes Catalyzed Sustainable Synthesis of 3,4-Dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxides via Acceptorless Dehydrogenative Coupling of Primary Alcohols.

We report the atom-economic and sustainable synthesis of biologically important 3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxide (DHBD) derivatives from readily available aromatic primary alcohols and 2-aminobenzenesulfonamide catalyzed by nickel(II)-N∧N∧S pincer-type complexes. The synthesized nickel complexes have been well-studied by elemental and spectroscopic (FT-IR, NMR, and HRMS) analyses. The solid-state molecular structure of complex 2 has been authenticated by a single-crystal X-ray diffraction study. Furthermore, a series of 3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxide derivatives have been synthesized (24 examples) utilizing a 3 mol % Ni(II) catalyst through acceptorless dehydrogenative coupling of benzyl alcohols with benzenesulfonamide. Gratifyingly, the catalytic protocol is highly selective with the yield up to 93% and produces eco-friendly water/hydrogen gas as byproducts. The control experiments and plausible mechanistic investigations indicate that the coupling of the in situ generated aldehyde with benzenesulfonamide leads to the desired product. In addition, a large-scale synthesis of one of the thiadiazine derivatives unveils the synthetic usefulness of the current methodology.

β‐Alkylation through Dehydrogenative Coupling of Primary Alcohols and Secondary Alcohols Catalyzed by Thioether‐Functionalized N‐Heterocyclic Carbene Ruthenium Complexes

AbstractA catalytic system for the direct β‐alkylation of secondary alcohol with primary alcohol has been investigated. In this work, a series of cationic Ru(II)(η6‐p‐cymene) complexes with thioether‐functionalized N‐heterocyclic carbene ligands (imidazole‐based 1 a–l and benzimidazole‐based 2 a–e) have been successfully synthesized and evaluated as catalysts. This investigation shows that modifications in the ligand moiety (thioether group and/or NHC core) have a strong effect on both selectivity and reactivity. Imidazole‐based complex 1 c, with only 1 mol % of catalyst loading, displayed the best catalytic activity as well as the highest selectivity for the β‐alcohol up to 98 : 2 for this tandem borrowing hydrogen/aldol methodology. Applied to a wide range of substrates, β‐alkylated secondary alcohols have been obtained in moderate yields, but generally with complete conversion and very high selectivity.

Ruthenium complexes of 1,4-diazabutadiene ligands with a cis-RuCl2 moiety for catalytic acceptorless dehydrogenation of alcohols: DFT evidence of chemically non-innocent ligand participation.

The acceptorless dehydrogenative coupling (ADC) of primary alcohols to esters by diazabutadiene-coordinated ruthenium compounds is reported. Treatment of cis-Ru(dmso)4Cl2 in acetone at 56 °C with different 1,4-diazabutadienes [p-XC6H4N[double bond, length as m-dash]C(H)(H)C[double bond, length as m-dash]NC6H4X-p; X = H, CH3, OCH3, and Cl; abbreviated as DAB-X], gives trans-Ru[κ2-N,N-DAB-X]2Cl2 as the kinetic product of substitution. Heating these products in o-xylene at 144 °C gives the thermodynamically favored cis-Ru[κ2-N,N-DAB-X]2Cl2 isomers. Electronic structure calculations confirm the greater stability of the cis diastereomer. The molecular structures for each pair of geometric isomers have been determined by X-ray diffraction analyses. Cyclic voltammetry experiments on the complexes show an oxidative response and a reductive response within 0.50 to 0.93 V and -0.76 to -1.24 V vs. SCE respectively. The cis-Ru[κ2-N,N-DAB-X]2Cl2 complexes function as catalyst precursors for the acceptorless dehydrogenative coupling of primary alcohols to H2 and homo- and cross-coupled esters. When 1,4-butanediol and 1,5-pentanediol are employed as substrates, lactones and hydroxyaldehydes are produced as the major dehydrogenation products, while secondary alcohols afforded ketones in excellent yields. The mechanism for the dehydrogenation of benzyl alcohol to benzyl benzoate and H2 using cis-Ru[κ2-N,N-DAB-H]2Cl2 (cis-1) as a catalyst precursor was investigated by DFT calculations. The data support a catalytic cycle that involves the four-coordinate species Ru[κ2-N,N-DAB-H][κ1-N-DAB-H](κ1-OCH2Ph) whose protonated κ1-diazabutadiene moiety functions as a chemically non-innocent ligand that facilitates a β-hydrogen elimination from the κ1-O-benzoxide ligand to give the corresponding hydride HRu[κ2-N,N-DAB-H][κ1-N-DAB-H](κ2-O,C-benzaldehyde). H2 production follows a Noyori-type elimination to give (H2)Ru[κ2-N,N-DAB-H][κ1-N-DAB-H](κ1-O-benzaldehyde) as an intermediate in the catalytic cycle.

One‐pot synthesis of 1,3‐disubstituted imidazo[1,5‐a]pyridines via acceptorless dehydrogenative coupling of primary alcohols promoted by binuclear ruthenium(II) N^O‐chelating complexes

A simple, straightforward and atom economic strategy to the synthesis of 1,3‐disubstituted imidazo[1,5‐a]pyridines using binuclear ruthenium(II) catalyst through acceptorless dehydrogenative coupling of primary alcohols with 2‐benzoylpyridine has been presented. New binuclear arene Ru(II) N^O chelating complexes of common formula [(η6‐benzene)2Ru2Cl2(μ‐L)], L = bis (furoylhydrazone) derivatives (1–3) were synthesized and characterized by analytical and spectral (FT‐IR, NMR and HR‐MS) techniques. The solid‐state molecular structure of one of the complexes (complex 1) has been authorized by single‐crystal XRD method. Further, a wide range of 1,3‐disubstituted imidazo[1,5‐a]pyridine derivatives have been successfully attained in good to excellent yields using binuclear arene Ru(II) catalysts with 1.0 mol% of catalyst loading. Further, control experiments unveil that the dehydrogenative coupling reaction mechanism proceeds via the formation of aldehyde and imine intermediates. The overall catalytic system releases H2 and water as only valuable by‐products.

Direct synthesis of benzimidazoles by Pd(II) N^N^S-pincer type complexes via acceptorless dehydrogenative coupling of alcohols with diamines

A sustainable synthetic method for the construction of substituted benzimidazoles via acceptorless dehydrogenative coupling of primary alcohols by palladium catalysts is reported. Three new non-classical symmetric Pd(II) N^N^S pincer complexes (1–3) were synthesized and characterized by spectral (FT-IR, UV-vis, NMR and ESI-MS) and analytical techniques. Moreover, the distorted square planar geometry of the synthesized complexes 1 and 2 was confirmed by single-crystal X-ray diffraction study. A wide range of benzimidazole derivatives (32 examples) up to 94% isolated yield has been derived via acceptorless dehydrogenative coupling of primary alcohols with derivatives of o-phenylenediamines. The present protocol operates smoothly with only 1 mol% catalyst loading. Furthermore, the mechanistic investigation with the aid of control experiments revealed that the reaction proceeded through in situ generation of aldehyde intermediate and generates hydrogen and water as the only byproducts.

Dehydrogenative Esterification and Dehydrative Etherification by Coupling of Primary Alcohols Based on Catalytic Function Switching of an Iridium Complex

AbstractEsters and ethers are widely used in modern organic synthesis. In recent years, the synthesis of esters by the dehydrogenative coupling of primary alcohols has been reported to be an environmentally benign process. In this situations, if a single catalyst can be used for the synthesis of either esters or ethers by making slight alterations to the reaction conditions, the value of the synthetic methodology would increase. In this study, we successfully developed a new catalytic function switching system: not only dehydrogenative esterification but also dehydrative etherification under environmentally friendly conditions were accomplished by the employment of a single iridium catalyst based on catalytic function switching. Using benzyl alcohol as a starting material, the esterification product, benzyl benzoate, and the etherification product, dibenzyl ether, were obtained in 92 % and 89 % yields, respectively, by employing same iridium catalyst precursor bearing a dihydroxybipyridine ligand, under optimized conditions.

Dehydrogenative Intramolecular Macrolactonization of Dihydroxy Compounds Using Ru-MACHO Catalyst.

Herein, we have developed a new approach for the synthesis of 11 to 21-membered macrolactones via intramolecular dehydrogenative coupling of primary alcohols by using Ru-MACHO as a catalyst and Cs2CO3 as a base. This protocol generated 11-21-ring-sized macrocycles (26 derivatives), free from an external oxidant or an additive, eliminating stoichiometric reagents and producing only hydrogen as a byproduct.

Half‐Sandwich Ruthenium Complexes Bearing Hemilabile κ2‐(C,S)−Thioether‐Functionalized NHC Ligands: Application to Amide Synthesis from Alcohol and Amine

AbstractAmide synthesis is one of the most crucial transformations in chemistry and biology. Among various catalytic systems, N‐heterocyclic carbene (NHC)‐based ruthenium (Ru) catalyst systems have been proven to be active for direct synthesis of amides by sustainable acceptorless dehydrogenative Coupling of primary alcohols with amines. Most often, these catalytic systems usually use monodentate NHC and thus require an additional ligand to obtain high reactivity and selectivity. In this work, a series of cationic Ru(II)(η6‐p‐cymene) complexes with thioether‐functionalized N‐heterocyclic carbene ligands (imidazole and benzimidazole‐based) have been prepared and fully characterized. These complexes have then been used in the amidation reaction and the most promising one (i. e. 3 c) has been applied on a large range of substrates. High conversions albeit with moderate yields have generally been obtained.

Tuning the selectivity in iridium-catalyzed acceptorless dehydrogenative coupling of primary alcohols.

An acceptorless dehydrogenative coupling of primary alcohols to carboxylic acids/carboxylates, esters, and Guerbet alcohols (via both homo- and cross-β-alkylation of the alcohols) in the presence of an N-heterocyclic carbene iridium(I) catalyst was developed under aerobic conditions. The product selectivity can be easily tuned among the products with a single catalyst through simple modification of the reaction conditions, such as the catalyst and base amounts, the choice of base, and the reaction temperature.

Nickel Complexes Bearing N,N,O-Tridentate Salicylaldiminato Ligand: Efficient Catalysts for Imines Formation via Dehydrogenative Coupling of Primary Alcohols with Amines

Nickel Complexes Bearing N,N,O-Tridentate Salicylaldiminato Ligand: Efficient Catalysts for Imines Formation via Dehydrogenative Coupling of Primary Alcohols with Amines

Visible-Light-Driven Dehydrogenative Coupling of Primary Alcohols with Phenols Forming Aryl Carboxylates.

A preparative method for obtaining aryl esters from aliphatic primary alcohols and phenols was developed. The reaction proceeds under the irradiation of visible light at ambient temperature, dispensing with any oxidant or hydrogen acceptor. Primary alcohols having a variety of functional groups are successfully esterified with phenols. The produced esters can be utilized as the precursor of various carbonyl compounds.

Cobalt embedded in nitrogen-doped porous carbon as a robust heterogeneous catalyst for the atom-economic alcohol dehydrogenation to carboxylic acids

Herein, cobalt embedded in nitrogen-doped porous carbon (Co@NC) was developed as a robust heterogeneous catalyst for the dehydrogenative coupling of primary alcohols and hydroxides. With Co@NC as the first earth-abundant metal/carbon composite material for this transformation, numerous aromatic and aliphatic carboxylic acids were efficiently afforded. Notably, the newly prepared Co@NC was fabricated in a facile and straightforward manner and reused up to 15 recycle rounds without activity decay. It is also worth emphasizing that the catalyst recycling was realized via magnetic separation with no special treatment or activation. Additionally, further experiments elucidated the pivotal role of the cobalt and nitrogen elements dispersed in the carbon matrix as well as the hierarchical porosity (micro-/meso-pores) in the catalytic activity and recyclability. Considering the active sites of Co@NC, we envisioned that the Co–N species was the most active site, while other active sites such as Co–O, Co0 species and free N-doped carbon were also present, but demonstrating lower activity or stability in comparison with the Co–N species. Additional mechanistic investigations were carried out to gain more insights into the possible reaction pathways. We found that the aldehyde was identified as a crucial intermediate, and two possible pathways were proposed for this catalytic process.

Iron-Catalyzed Acceptorless Dehydrogenative Coupling of Alcohols With Aromatic Diamines: Selective Synthesis of 1,2-Disubstituted Benzimidazoles.

Benzimidazoles are important N-heteroaromatic compounds with various biological activities and pharmacological applications. Herein, we present the first iron-catalyzed selective synthesis of 1,2-disubstituted benzimidazoles via acceptorless dehydrogenative coupling of primary alcohols with aromatic diamines. The tricarbonyl (η4-cyclopentadienone) iron complex catalyzed dehydrogenative cyclization, releasing water and hydrogen gas as by-products. The earth abundance and low toxicity of iron metal enable the provision of an eco-friendly and efficient catalytic method for the synthesis of benzimidazoles.

DFT Study of PNP-Mn-Catalyzed Acceptorless Dehydrogenative Coupling of Primary Alcohols with Hydrazine to Give Alkene or Azine

A density functional theory (DFT) study has been carried out to gain insight into the acceptorless dehydrogenative coupling (ADC) reactions of primary alcohols with hydrazine to afford alkene or az...

The role of the metal-bound N–H functionality in Noyori-type molecular catalysts

Noyori-type catalysts have found numerous applications in research and industrial settings. The central mechanistic component of such catalysts is a metal centre coordinated to a N–H moiety. This amino moiety has traditionally been thought to participate directly in catalytic reactions by serving as a H+ donor, with the resulting amido group then serving as a H+ acceptor. This traditional understanding has been supplanted by more recent studies that instead suggest that the N–H group(s) (or N–Ma group(s) obtained in the reaction with a base of an alkali metal Ma) serve to stabilize rate-determining transition states through non-covalent N–X···O interactions (X = H or Ma). Thus, N–X bonds are actually not cleaved or formed in many catalytic cycles. This Review describes examples of metal–ligand bifunctional catalysts relevant to reactions involving H2 or its equivalents, emphasizing systems that have been applied in industry. Subsequently, a summary of our present understanding of the Noyori–Ikariya and Noyori reaction mechanisms is presented, which we compare to topical related reactions such as MeOH dehydrogenation, ester and carboxamide hydrogenation and the dehydrogenative coupling of primary alcohols with other alcohols and amines. This mechanistic understanding allows us to identify the design principles that may potentially afford improved molecular catalysts and that may unravel a distinct mechanism for H2 production by the diiron hydrogenase enzymes. Noyori-type catalysts perform (de)hydrogenation and transfer (de)hydrogenation reactions at a metal centre coordinated to a N–H moiety. Understanding how these metal–ligand bifunctional catalysts operate enables us to design better catalysts for these reactions and for related conversions such as alcohol dehydrogenations, ester or carboxamide hydrogenations and dehydrogenative coupling of primary alcohols with other alcohols or amines.

Cobalt-Catalyzed Acceptorless Dehydrogenative Coupling of Primary Alcohols to Esters.

A novel catalytic system with a tripodal cobalt complex is developed for efficiently converting primary alcohols to esters. KO tBu is found essential to the transformation. A preliminary mechanistic study suggests a plausible reaction route that involves an initial Co-catalyzed dehydrogenation of alcohol to aldehyde, followed by a Tishchenko-type pathway to ester mediated by KO tBu.

Direct Synthesis of Benzimidazoles by Dehydrogenative Coupling of Aromatic Diamines and Alcohols Catalyzed by Cobalt

Herein, we present the base-metal-catalyzed dehydrogenative coupling of primary alcohols and aromatic diamines to selectively form functionalized 2-substituted benzimidazoles, liberating water and hydrogen gas as the sole byproducts. The reaction is catalyzed by pincer complexes of Earth-abundant cobalt under base-free conditions.

Rethinking the Dehydrogenative Amide Synthesis

This paper is concerned with the mechanism of the catalytic dehydrogenative coupling of primary alcohols with amines; it addresses the question on what happens to the aldehyde produced in the catalytic solution upon dehydrogenation of an alcohol substrate. Here we demonstrate a rapid catalytic reaction of acetaldehyde with primary amines, leading to acetamides. The facile amide bond formation is a low-energy, outer-sphere catalytic process elucidated with the help of DFT calculations. Overall, the dehydrogenative amide synthesis comprises two metal-catalyzed cycles: the first producing the aldehyde and H2, and the second where the hemiaminal is formed and is dehydrogenated. The results call into question the existing mechanistic ideas (reviewed by Li and Hall) that invoke the uncatalyzed formation of a free hemiaminal intermediate and assume that the hemiaminal dehydrogenation requires a 16-electron catalyst.

Acceptorless dehydrogenative coupling of primary alcohols to esters by heterogeneous Pt catalysts

Supported platinum catalysts have been studied for the acceptor-free dehydrogenative coupling of primary alcohols to esters in the liquid phase under solvent-free conditions in N2 at 180 °C. The activity depends on the support material, and Pt-loaded SnO2 (Pt/SnO2) gives the highest activity. Pt/SnO2 shows higher activity than various transition metals (Ir, Re, Ru, Rh, Pd, Ag, Co, Ni, Cu) loaded on SnO2. The Pt/SnO2 catalyst (1 mol%) selectively converted various primary alcohols to their corresponding esters in moderate to high isolated yield (53–91%). This is the first example of reusable heterogeneous catalysts for the acceptor-free dehydrogenative coupling of primary alcohols to esters under additive-free and solvent-free conditions. Mechanistic and infrared (IR) studies are also shown to discuss the reaction pathway and a possible role of the SnO2 support as Lewis acid sites that activate carbonyl groups of adsorbed aldehyde intermediates.

ChemInform Abstract: Formation of Tertiary Amides and Dihydrogen by Dehydrogenative Coupling of Primary Alcohols with Secondary Amines Catalyzed by Ruthenium Bipyridine‐Based Pincer Complexes.

AbstractThe direct amidation of primary alcohols with challenging secondary amines is achieved in the presence of small amounts of Ru‐catalysts.