Ekambaram Balaraman

Efficient hydrogenation of organic carbonates, carbamates and formates indicates alternative routes to methanol based on CO2 and CO

Catalytic hydrogenation of organic carbonates, carbamates and formates is of significant interest both conceptually and practically, because these compounds can be produced from CO2 and CO, and their mild hydrogenation can provide alternative, mild approaches to the indirect hydrogenation of CO2 and CO to methanol, an important fuel and synthetic building block. Here, we report for the first time catalytic hydrogenation of organic carbonates to alcohols, and carbamates to alcohols and amines. Unprecedented homogeneously catalysed hydrogenation of organic formates to methanol has also been accomplished. The reactions are efficiently catalysed by dearomatized PNN Ru(II) pincer complexes derived from pyridine- and bipyridine-based tridentate ligands. These atom-economical reactions proceed under neutral, homogeneous conditions, at mild temperatures and under mild hydrogen pressures, and can operate in the absence of solvent with no generation of waste, representing the ultimate ‘green’ reactions. A possible mechanism involves metal–ligand cooperation by aromatization–dearomatization of the heteroaromatic pincer core. Producing methanol — useful as both a fuel and a synthetic building block — from carbon monoxide and carbon dioxide has been achieved using homogeneous catalytic hydrogenation of carbonates, carbamates and formates. The catalyst is a dearomatized ruthenium(II) pincer complex and the reaction proceeds efficiently under mild conditions.

Direct Hydrogenation of Amides to Alcohols and Amines under Mild Conditions

The selective, direct hydrogenation of amides to the corresponding alcohols and amines with cleavage of the C-N bond was discovered. The expected products of C-O cleavage are not formed (except as traces in the case of anilides). The reaction proceeds under mild pressure and neutral, homogeneous conditions using a dearomatized, bipyridyl-based PNN Ru(II) pincer complex as a catalyst. The postulated mechanism involves metal-ligand cooperation by aromatization-dearomatization of the heteroaromatic pincer core and does not involve hydrolytic cleavage of the amide. The simplicity, generality, and efficiency of this environmentally benign process make it attractive for the direct transformations of amides to alcohols and amines in good to excellent yields.

Catalytic transformation of alcohols to carboxylic acid salts and H2 using water as the oxygen atom source

The oxidation of alcohols to carboxylic acids is an important industrial reaction used in the synthesis of bulk and fine chemicals. Most current processes are performed by making use of either stoichiometric amounts of toxic oxidizing agents or the use of pressurized dioxygen. Here, we describe an alternative dehydrogenative pathway effected by water and base with the concomitant generation of hydrogen gas. A homogeneous ruthenium complex catalyses the transformation of primary alcohols to carboxylic acid salts at low catalyst loadings (0.2 mol%) in basic aqueous solution. A consequence of this finding could be a safer and cleaner process for the synthesis of carboxylic acids and their derivatives at both laboratory and industrial scales. The development of a catalytic, mild and atom-economical transformation of alcohols to carboxylic acid salts and hydrogen gas is described. The reaction uses water as a source of oxygen, with a homogenous Ru catalyst at low (0.2 mol%) catalyst loadings in basic aqueous solution.

Synthesis of Peptides and Pyrazines from β‐Amino Alcohols through Extrusion of H2 Catalyzed by Ruthenium Pincer Complexes: Ligand‐Controlled Selectivity

Peptides constitute one of the most important families of compounds in chemistry and biology. Short peptides have found intriguing biological and synthetic applications. For example, the conformational rigidity of cyclic peptides makes them attractive for drug discovery and biomedical research. Several cyclic peptides that show intriguing biological activity are found in nature. Cyclic peptides have been discovered that are novel antibiotics, enzyme inhibitors, and receptor antagonists. Among them are the smallest cyclopeptides, 2,5diketopiperazines derivatives, which are commonly found as natural products. These compounds exhibit high-affinity binding to a large variety of receptors and show a broad range of biological acitivities, including antimicrobial, antitumoral, antiviral, and neuroprotective effects. 2,5-diketopiperazine derivatives are synthesized in solution or on the solid phase from commercially available and appropriately protected chiral a-amino acids in processes that are usually not atom-economical and generate considerable amounts of waste. Large libraries of cyclic peptides are accessible through solid-phase split-and-pool synthesis, and various methods were developed for their syntheses. Very recently, the synthesis of diketopiperazines from amino acids under microwave irradiation was reported. Green, atom-economical methods for the generation of peptides are highly desirable. We have developed several reactions catalyzed by PNN and PNP Ru pincer complexes based on pyridine, bipyridine, 13] and acridine and have discovered a new mode of metal–ligand cooperation based on ligand aromatization–dearomatization. For example, the PNN Ru pincer complex 1 (Scheme 1) catalyzes the direct synthesis of amides from alcohols and amines with liberation of H2 [17] (Scheme 2, Eq. (1)). Several reports on amide formation by dehydrogenative coupling of amines with alcohols appeared later. Unlike complex 1, the analogous PNP complex 2 (or complex 3 in the presence of an equivalent of base) catalyzes the coupling of amines with alcohols to form imines rather than amides with liberation of H2 and H2O (Scheme 2, Eq. (2)). Herein we report a novel method for peptide synthesis, which involves dehydrogenative coupling of b-amino alcohols with extrusion of H2 catalyzed by complex 1. This environmentally benign and atom-economical reaction proceeds under neutral reaction conditions without the use of toxic reagents, activators, condensing agents, or other additives. With the analogous PNP complex 2, a strikingly different reaction takes place, which leads to pyrazines with extrusion of H2 and H2O. Initially, we were interested to see whether coupling of bamino alcohols with amines can be accomplished and whether racemization would be involved. Reaction of (S)-2-amino-3phenylpropan-1-ol (4), benzylamine, and 1 mol% of the catalyst 1 in toluene at reflux for six hours led to (S)-2-aminoN-benzyl-3-phenylpropanamide 5 in 58% yield after column chromatography (Scheme 3). The specific rotation of amide 5 obtained from the catalysis is essentially the same as reported (+ 16.08). The neutral reaction conditions likely help to prevent racemization. Scheme 1. PNNand PNP-type pincer ruthenium complexes.

Transition-metal-catalyzed hydrogen-transfer annulations: access to heterocyclic scaffolds.

The ability of hydrogen-transfer transition-metal catalysts, which enable increasingly rapid access to important structural scaffolds from simple starting materials, has led to a plethora of research efforts on the construction of heterocyclic scaffolds. Transition-metal-catalyzed hydrogen-transfer annulations are environmentally benign and highly atom-economical as they release of water and hydrogen as by-product and utilize renewable feedstock alcohols as starting materials. Recent advances in this field with respect to the annulations of alcohols with various nucleophilic partners, thus leading to the formation of heterocyclic scaffolds, are highlighted herein.

Cobalt-Catalyzed Bis-alkynylation of Amides via Double C–H Bond Activation

The first example of cobalt-catalyzed selective bis-alkynylation of amides via double C-H bond activation with the directing assistance of a removable bidentate auxiliary is reported. The developed alkynylation strategy is simple, efficient, and tolerant of various functional groups including ether, amine, halides, and heterocyclic motifs. The reaction can be scaled up under mild conditions.

Stepwise Metal–Ligand Cooperation by a Reversible Aromatization/Deconjugation Sequence in Ruthenium Complexes with a Tetradentate Phenanthroline-Based Ligand

The synthesis and reactivity of ruthenium complexes containing the tetradentate phenanthroline-based phosphine ligand 2,9-bis((di-tert-butylphosphino)methyl)-1,10-phenanthroline (PPhenP) is described. The hydrido chloro complex [RuHCl(PPhenP)] (2) undergoes facile dearomatization upon deprotonation of the benzylic position, to give [RuH(PPhenP-H)] (4). Addition of dihydrogen to 4 causes rearomatization of the phenanthroline moiety to trans-[Ru(H)(2)(PPhenP)] (5), followed by hydrogenation of an aromatic heterocycle in the ligand backbone, to give a new dearomatized and deconjugated complex [RuH(PPhenP*-H)] (6). These aromatization/deconjugation steps of the coordinated ligand were demonstrated to be reversible and operative in the dehydrogenation of primary alcohols without the need for a hydrogen acceptor. This aromatization/deconjugation sequence constitutes an unprecedented mode of a stepwise cooperation between the metal center and the coordinated ligand.

Reversed reactivity of anilines with alkynes in the rhodium-catalysed C–H activation/carbonylation tandem

Development of multicatalytic approach consisting of two or more mechanistically distinct catalytic steps using a single-site catalyst for rapid and straightforward access of structurally complex molecules under eco-benign conditions has significance in contemporary science. We have developed herein a rhodium-catalysed C–H activation strategy which uses an unprotected anilines and an electron-deficient alkynes to C–C bonded products as a potential intermediate in contrast to the archetypical C–N bonded products with high levels of regioselectivity. This is followed by carbonylation of C–H bond activated intermediate and subsequent annulation into quinolines has been described. This rhodium-catalysed auto-tandem reaction operates under mild, environmentally benign conditions using water as the solvent and CO surrogates as the carbonyl source with the concomitant generation of hydrogen gas. The strategy may facilitate the development of new synthetic protocols for the efficient and sustainable production of chemicals in an atom-economic way from simple, abundant starting materials.

Direct Synthesis of Secondary Amines From Alcohols and Ammonia Catalyzed by a Ruthenium Pincer Complex

Efficient and selective direct synthesis of secondary amines from primary alcohols and ammonia with liberation of water has been achieved, with high turnover numbers and with no generation of waste. In case of benzylic alcohols, imines rather than amines are obtained. This atom economical, environmentally benign reaction is homogenously catalyzed by a well-defined bipyridine based Ru(II)-PNN pincer complex.Graphical Abstract

Predesigned Metal-Anchored Building Block for In Situ Generation of Pd Nanoparticles in Porous Covalent Organic Framework: Application in Heterogeneous Tandem Catalysis

The development of nanoparticle-polymer-hybrid-based heterogeneous catalysts with high reactivity and good recyclability is highly desired for their applications in the chemical and pharmaceutical industries. Herein, we have developed a novel synthetic strategy by choosing a predesigned metal-anchored building block for in situ generation of metal (Pd) nanoparticles in the stable, porous, and crystalline covalent organic framework (COF), without using conventional reducing agents. In situ generation of Pd nanoparticles in the COF skeleton is explicitly confirmed from PXRD, XPS, TEM images, and 15N NMR spectral analysis. This hybrid material is found to be an excellent reusable heterogeneous catalyst for the synthesis of biologically and pharmaceutically important 2-substituted benzofurans from 2-bromophenols and terminal alkynes via a tandem process with the turnover number up to 1101. The heterogeneity of the catalytic process is unambiguously verified by a mercury poisoning experiment and leaching test. This hybrid material shows superior catalytic performance compared to commercially available homogeneous as well as heterogeneous Pd catalysts.