Acceptorless Dehydrogenative Coupling Research Articles

A Simple Iron-Catalyst for Alkenylation of Ketones Using Primary Alcohols.

Herein, we developed a simple iron-catalyzed system for the α-alkenylation of ketones using primary alcohols. Such acceptor-less dehydrogenative coupling (ADC) of alcohols resulted in the synthesis of a series of important α,β-unsaturated functionalized ketones, having aryl, heteroaryl, alkyl, nitro, nitrile and trifluoro-methyl, as well as halogen moieties, with excellent yields and selectivity. Initial mechanistic studies, including deuterium labeling experiments, determination of rate and order of the reaction, and quantitative determination of H2 gas, were performed. The overall transformations produce water and dihydrogen as byproducts.

Synthesis of Pyridines, Quinolines, and Pyrimidines via Acceptorless Dehydrogenative Coupling Catalyzed by a Simple Bidentate P^N Ligand Supported Ru Complex

A ruthenium hydrido chloride complex (1) supported by a simple, heteroleptic bidentate P^N ligand (L1) containing a diarylphosphine and a benzannulated phenanthridine donor arm is reported. In the ...

Application of a reusable Co-based nanocatalyst in alcohol dehydrogenative coupling strategy: Synthesis of quinoxaline and imine scaffolds

A nitrogen doped carbon supported cobalt catalyzed efficient synthesis of imines and quinoxaline motifs is reported. Co(OAc)2-Phen/Carbon-800 (Co-phen/C-800) showed the superior reactivity compared to other materials prepared at different temperature, in the synthesis of quinoxalines by the coupling between diamines and diols. Moreover, applying the transfer hydrogenation and acceptorless dehydrogenative coupling strategy, imines and quinoxaline derivatives were synthesized from the nitro compounds. The practical applicability of this protocol was demonstrated by the gram-scale synthesis and the reusability of the catalyst upto 8th cycle. Furthermore, several kinetic experiments were carried out to realize the probable mechanism.

Acceptorless dehydrogenative coupling with Ru-based catalysts for the synthesis of N-heteroaromatic compounds.

Ru-Catalyzed acceptorless dehydrogenative coupling (ADC) and auto-transfer-hydrogenative (ATH) reactions are effective, versatile transformations for the constructions of N-heteroaromatic compounds from alcohols. Water and hydrogen are the by-products and the starting alcohols are less toxic, more readily available and more easily handled than their halogenated counterparts. A variety of homogeneous ruthenium catalysts, alcohols and partner-substrates such as amines, ammonia, amidines and nitriles, have been used to build N-heteroaromatic compounds in one-pot, multi-step syntheses. This review details recently reported Ru catalysts employed for these reactions, describing the scope of each methodology, proposed reaction mechanisms, regioselectivity of coupling and applications in synthesis.

Synthesis of oxalamides by acceptorless dehydrogenative coupling of ethylene glycol and amines and the reverse hydrogenation catalyzed by ruthenium.

A sustainable, new synthesis of oxalamides, by acceptorless dehydrogenative coupling of ethylene glycol with amines, generating H2, homogeneously catalyzed by a ruthenium pincer complex, is presented. The reverse hydrogenation reaction is also accomplished using the same catalyst. A plausible reaction mechanism is proposed based on stoichiometric reactions, NMR studies, X-ray crystallography as well as observation of plausible intermediates.

A Highly Selective Manganese-Catalyzed Synthesis of Imines under Phosphine-Free Conditions

An efficient and highly selective phosphine-free NN-manganese(I) complex catalyst system was developed for the acceptorless dehydrogenative coupling of alcohols with amines to form imines. The coupling reactions underwent at 3 mol % catalyst loading, and a large range of alcohols and amines with diverse functional groups was applied, including challenging diol and diamine. The target imine products were obtained in good to excellent yields. The present work provides an alternative method to construct highly active nonprecious metal complex catalysts based on phosphine-free ligands.

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...

Polymer-Anchored Bifunctional Pincer Catalysts for Chemoselective Transfer Hydrogenation and Related Reactions.

A series of polymer-supported cooperative PC(sp3 )P pincer catalysts was synthesized and characterized. Their catalytic activity in the acceptorless dehydrogenative coupling of alcohols and the transfer hydrogenation of aldehydes with formic acid as a hydrogen source was investigated. This comparative study, examining homogeneous and polymer-tethered species, proved that carefully designing a link between the support and the catalytic moiety, which takes into consideration the mechanism underlying the target transformation, might lead to superior heterogeneous catalysis.

Formamides as Isocyanate Surrogates: A Mechanistically Driven Approach to the Development of Atom-Efficient, Selective Catalytic Syntheses of Ureas, Carbamates, and Heterocycles.

Despite the hazardous nature of isocyanates, they remain key building blocks in bulk and fine chemical synthesis. By surrogating them with less potent and readily available formamide precursors, we herein demonstrate an alternative, mechanistic approach to selectively access a broad range of ureas, carbamates, and heterocycles via ruthenium-based pincer complex catalyzed acceptorless dehydrogenative coupling reactions. The design of these highly atom-efficient procedures was driven by the identification and characterization of the relevant organometallic complexes, uniquely exhibiting the trapping of an isocyanate intermediate. Density functional theory (DFT) calculations further contributed to shed light on the remarkably orchestrated chain of catalytic events, involving metal-ligand cooperation.

Selective Ketone Formations via Cobalt-Catalyzed β-Alkylation of Secondary Alcohols with Primary Alcohols.

A homogeneous cobalt-catalyzed β-alkylation of secondary alcohols with primary alcohols to selectively synthesize ketones via acceptorless dehydrogenative coupling is reported for the first time. Notably, this transformation is environmentally benign and atom economical with water and hydrogen gas as the only byproducts.

Direct Synthesis of Amides by Acceptorless Dehydrogenative Coupling of Benzyl Alcohols and Ammonia Catalyzed by a Manganese Pincer Complex: Unexpected Crucial Role of Base.

Amide synthesis is one of the most important transformations in chemistry and biology. The direct use of ammonia for the incorporation of nitrogen functionalities in organic molecules is an attractive and environmentally benign method. We present here a new synthesis of amides by acceptorless dehydrogenative coupling of benzyl alcohols and ammonia. The reaction is catalyzed by a pincer complex of earth-abundant manganese in the presence of a stoichiometric base, making the overall process economical, efficient, and sustainable. Interesting mechanistic insights based on detailed experimental observations, indicating the crucial role of the base, are provided.

Nickel-Catalyzed Direct Alkenylation of Methyl Heteroarenes with Primary Alcohols

An efficient nickel-catalyzed acceptorless dehydrogenative coupling of methyl-substituted heteroarenes with primary alcohols is achieved using an in situ generated complex of inexpensive NiBr2 and readily available 8-aminoquinoline picolinic amide ligand. The protocol is operationally simple and scalable and furnishes a series of high-value 2-alkenylheteroarenes in good yields (up to 88%) with exclusive E-selectivity. The reaction proceeds with the release of water and molecular hydrogen, which was analyzed through gas chromatography to validate the reaction mechanism.

In Situ Generated Cobalt Catalyst for the Dehydrogenative Coupling of Alcohols and Amines into Imines

AbstractAn in situ formed cobalt catalyst is developed from cobalt(II)bromide, bis[2‐(diisopropylphosphino)‐4‐methylphenyl]amine and zinc metal. The catalyst mediates the acceptorless dehydrogenative coupling of alcohols and amines into imines with the release of hydrogen gas and the transformation is applied to the synthesis of a variety of imines from different alcohols and amines. The mechanism is investigated with labelled substrates and based on the results a cobalt(I) PNP complex is believed to be the catalytically active species which abstracts hydrogen gas from the alcohol through a metal ligand bifunctional pathway.

Phosphine Ligand‐Free Ruthenium Complexes as Efficient Catalysts for the Synthesis of Quinolines and Pyridines by Acceptorless Dehydrogenative Coupling Reactions

AbstractA series of phosphine‐free Ru(III)/Ru(II) complexes of NH functionalized N˄N˄N pincer ligands exhibit excellent activity for acceptorless dehydrogenative coupling (ADC) of secondary alcohols with 2‐aminobenzyl or γ‐amino alcohols to quinolines and pyridines. Ru(III) complexes [LRuCl3] (L=6‐(3‐R1,5‐R2‐1H‐pyrazol‐1‐yl)‐N‐(pyridin‐2‐yl)pyridin‐2‐amine; 1 a: R1=R2=H (L1); 1 b: R1=R2=Me (L2); 1 c: R1=H, R2=CF3 (L3); 1 d: R1=H, R2=Ph (L4); 1bMe: L=6‐(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)‐N‐methyl‐N‐(pyridin‐2‐yl)pyridin‐2‐amine (L2Me)) were obtained by refluxing RuCl3 ⋅ xH2O with the corresponding ligand in EtOH. Five Ru(II) complexes [LRu(DMSO‐κS)Cl2] (2 a: L=L1; 2 b: L=L2; 2 c: L=L3; 2 d: L=L4; 2bMe: L=L2Me) were formed by reducing the corresponding Ru(III) complex in refluxing EtOH. The latter complexes could also be prepared directly by refluxing Ru(DMSO)4Cl2 with the corresponding ligand in EtOH. These Ru(III) and Ru(II) complexes, especially 1 b/2 b, exhibited high catalytic efficiency and broad functional group tolerance in ADC reactions of secondary alcohols with 2‐aminobenzyl or γ‐amino alcohols to quinolines and pyridines. A detail mechanistic study indicated the Ru(III) complex was reduced into the Ru(II) species, which is the active catalytic center for ADC via a Ru−H/N−H bifunctional outer‐sphere mechanism. This protocol provides a reliable, atom‐economical and environmentally benign procedure for C−N and C−C bond formation.

Pyridine-Based PCP-Ruthenium Complexes: Unusual Structures and Metal-Ligand Cooperation.

Metal-ligand cooperation (MLC) by dearomatization/aromatization provides a unique way for bond activation, which has led to the discovery of various acceptorless dehydrogenative coupling reactions. However, most of the studies are based on pincer complexes with a central nitrogen donor. Aiming at exploration of the possibility of MLC by PCP-type pincer complexes, we report herein the synthesis, characterization, structure, and reactivity of pyridine-based PCP-Ru complexes. X-ray structures and DFT calculations indicate a carbenoid character of quaternized pyridine-based PCP-Ru complexes. These complexes undergo dearomatization by direct deprotonation, and the dearomatized complex can react with hydrogen, alcohols, or nitriles to regain aromatization via MLC.

Palladium oxide nanoparticles intercalated mesoporous silica for solvent free acceptorless dehydrogenation reactions of alcohols

Abstract Aggregation-free well-dispersed palladium oxide nanoparticles intercalated into the walls of mesoporous silica (PdOMS) were prepared by using thioether groups during the sol-gel preparation of mesoporous silica. The PdOMS material was characterized by N2 adsorption-desorption, X-ray diffraction, scanning electron microscopy, transmission electron microscopy and UV–Vis spectroscopy. The material retains mesoporous structure with narrow pore size distribution with an average pore diameter of 6.8 nm and possesses high surface area of 683 m2g–1. The PdOMS catalyst was employed as an efficient heterogeneous catalyst in the acceptor- and oxidant-free dehydrogenation of neat alcohols to corresponding carbonyl compounds in very good to excellent yields (72–95%) at 80 °C under inert atmosphere. The catalytic efficacy of PdOMS has also been evaluated for the acceptorless dehydrogenative coupling reactions of alcohols with o-diamino benzene and o-amino phenol to yield azole-based heterocycles. The stability of PdOMS was assessed by investigating its recyclability and reusability in the dehydrogenation of neat alcohol for up to five cycles.

Phosphine-Free Well-Defined Mn(I) Complex-Catalyzed Synthesis of Amine, Imine, and 2,3-Dihydro-1H-perimidine via Hydrogen Autotransfer or Acceptorless Dehydrogenative Coupling of Amine and Alcohol

The application of nontoxic, earth-abundant transition metals in place of costly noble metals is a paramount goal in catalysis and is especially interesting if the air- and moisture-stable ligand s...

Manganese(III) Porphyrin-Catalyzed Dehydrogenation of Alcohols to form Imines, Tertiary Amines and Quinolines.

Manganese(III) porphyrin chloride complexes have been developed for the first time as catalysts for the acceptorless dehydrogenative coupling of alcohols and amines. The reaction has been applied to the direct synthesis of imines, tertiary amines and quinolines where only hydrogen gas and/or water are formed as the by-product(s). The mechanism is believed to involve the formation of a manganese(III) alkoxide complex which degrades into the aldehyde and a manganese(III) hydride species. The latter reacts with the alcohol to form hydrogen gas and thereby regenerates the alkoxide complex.

Synthesis of Unsymmetrical N-Heterocyclic Carbene–Nitrogen–Phosphine Chelated Ruthenium(II) Complexes and Their Reactivity in Acceptorless Dehydrogenative Coupling of Alcohols to Esters

Two novel ruthenium complexes RuH(CO)Cl(PPh3)(κ2-CP) (1) and [fac-RuH(CO)(PPh3)(κ3-CNP)]Cl (2) bearing unsymmetrical N-heterocyclic carbene–nitrogen–phosphine (CNP) were synthesized and characteriz...

Photoredox Mediated Acceptorless Dehydrogenative Coupling of Saturated N-Heterocycles

We report herein a direct unsymmetric coupling and controllable aromatization reaction of saturated N-heterocycles enabled by synergistic photoredox and acid catalysis. The reaction furnishes C2–C3...