Atom-economical Methodology Research Articles

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 %.

Cobalt(II)-Catalyzed Synthesis of γ-Diketones from Aryl Alkenes and Its Utilization in the Synthesis of Various Heterocyclic Compounds.

An earth-abundant Co(II) salt-catalyzed mild and affordable synthetic route has been developed for the synthesis of industrially relevant 1,4-dicarbonyl compounds (or γ-diketones) via oxidative coupling between aryl alkenes and ketones (both cyclic and acyclic) using TBHP and DBU as the oxidant and base, respectively. 1,4-Dicarbonyl compounds are known to be synthesized using expensive metal catalysts, dual catalysts, or low-cost metal complexes combined with an additive or ligand template, which further needs to be synthesized. Herein, we report the synthesis of 1,4-dicarbonyl compounds using cobalt(II) acetate as a catalyst without any expensive co-catalyst or ligand templates. This methodology has a broad substrate scope with significant yields and good functional group tolerance. Generation of unsymmetrical 1,4-dicarbonyls at room temperature and its versatile synthetic expansion to produce synthetically and biologically valuable heterocyclic compounds are salient features of this novel methodology. In addition, various controlled experiments such as primary kinetic isotope effect study, Hammett analysis with variation of the nature of the substituents on the styrene ring, and theoretical calculations (density functional theory) unravel the mechanistic intricacies involved in this new, simple, and atom-economic methodology.

Cu(II) Promoted C(sp3 )-H Activation in Unactivated Cycloalkanes: Oxo-Alkylation of Styrenes to Synthesize β-Disubstituted Ketones.

We report the Cu(II) catalyzed synthesis of β-disubstituted ketones from styrene via oxo-alkylation with unactivated cycloalkanes as the alkylating agent in presence of tert-butylhydroperoxide (TBHP) and 1-methylimidazole as oxidant and base respectively. β-disubstituted ketones are known to be synthesized by using either expensive Ru/Ir complexes, or low-cost metal complexes (e. g., Fe, Mn) with activated species like aldehyde, acid, alcohol, or phthalimide derivatives as the alkylating agent, however, use of unactivated cycloalkanes directly as the alkylating agent remains challenging. A wide range of aliphatic C-H substrates as well as various olefinic arenes and heteroarene (35 substrates including 14 new substrates) are well-tolerated in this method. Hammett analysis shed more light on the substitution effect in the olefinic part on the overall mechanism. Furthermore, the controlled experiments, kinetic isotope effect study, and theoretical calculations (DFT) enable us to gain deeper insight of mechanistic intricacies of this new simple and atom-economic methodology.

One‐pot Synthesis of Propargylamines using Aldehydes‐Amines‐Acetylene via an Efficient Nickel‐Based Silica‐Coated Magnetic Nanocatalyst

Highly proficient nickel-based magnetically retrievable nanocatalyst was synthesized, characterized and further utilized for A3 coupling of aldehydes-amines-acetylene for the one pot synthesis of propargylamines

Benzimidazole-based N[sbnd]heterocyclic carbene ruthenium(II) complexes: Synthesis and C[sbnd]H bond activation properties

The transition-metal-promoted CH activation has become an efficient as well as an atom-economic methodology for the synthesis of a wide array of organic molecules. Herein, the reaction of RuCl2(p-cymene)]2 with 1,3-dialkylbenzimidazolium salts (1a-c) in the presence of a small excess of cesium carbonate yields chelated η6-arene, η1-carbene ruthenium complexes (2a-c). All synthesized compounds were characterized by elemental analysis and NMR spectroscopy. The catalytic activity of [Cl2Ru(η6-arene, η1-carbene)] complexes (2a-c) were evaluated in the direct arylation of 2-phenylpyridine and 1-phenylpyrazole with (hetero)aryl chlorides derivative.

Ru(II)-Catalyzed Chemoselective C(sp3)-H Monoarylation of 8-Methyl Quinolines with Arylboronic Acids.

The transition-metal-promoted C-H activation has become an efficient as well as atom-economic methodology for the synthesis of a wide array of organic molecules, but the cost of the metal catalyst and selectivity remain the major challenges. Herein, the first [Cl2Ru(p-cymene)]2-catalyzed direct monoarylation of unactivated C(sp3)-H bonds of 8-methyl quinolines with arylboronic acids to synthesize diarylmethane compounds is presented. The transformation shows a broad substrate scope with high chemoselectivity for the synthesis of 8-benzyl quinolines. In the preliminary mechanistic studies, control experiments, deuterium labeling experiments, and kinetic studies have been performed.

Chemo- and Regioselective Synthesis of Acyl-Cyclohexenes by a Tandem Acceptorless Dehydrogenation-[1,5]-Hydride Shift Cascade

An atom-economical methodology to access substituted acyl-cyclohexenes from pentamethylacetophenone and 1,5-diols is described. This process is catalyzed by an iridium(I) catalyst in conjunction with a bulky electron rich phosphine ligand (CataCXium A) which favors acceptorless dehydrogenation over conjugate reduction to the corresponding cyclohexane. The reaction produces water and hydrogen gas as the sole byproducts and a wide range of functionalized acyl-cyclohexene products can be synthesized using this method in very high yields. A series of control experiments were carried out, which revealed that the process is initiated by acceptorless dehydrogenation of the diol followed by a redox-neutral cascade process, which is independent of the iridium catalyst. Deuterium labeling studies established that the key step of this cascade involves a novel base-mediated [1,5]-hydride shift. The cyclohexenyl ketone products could readily be cleaved under mildly acidic conditions to access a range of valuable substituted cyclohexene derivatives.

Direct Synthesis of Cycloalkanes from Diols and Secondary Alcohols or Ketones Using a Homogeneous Manganese Catalyst.

A method for the synthesis of substituted cycloalkanes was developed using diols and secondary alcohols or ketones via a cascade hydrogen borrowing sequence. A non-noble and air-stable manganese catalyst (2 mol %) was used to perform this transformation. Various substituted 1,5-pentanediols (3-4 equiv) and substituted secondary alcohols (1 equiv) were investigated to prepare a collection of substituted cyclohexanes in a diastereoselective fashion. Similarly, cyclopentane, cyclohexane, and cycloheptane rings were constructed from substituted 1,4-butanediol, 1,5-pentanediol, and 1,6-hexanediol, and sterically hindered ketones following a (4 + 1), (5 + 1), and (6 + 1) strategy, respectively. This reaction provides an atom economic methodology to construct two C-C bonds at a single carbon center generating high-value cycloalkanes from readily available alcohols as feedstock using an earth-abundant metal catalyst.

Catalyst-Free and Solvent-Free Facile Hydroboration of Imines.

A facile process for the catalyst-free and solvent-free hydroboration of aromatic as well as heteroaromatic imines is reported. This atom-economic methodology is scalable, compatible with sterically and electronically diverse imines, displaying excellent tolerance towards various functional groups, and works efficiently at ambient temperature in most of the cases, affording secondary amines in good to excellent yield after hydrolysis.

Palladium-Catalyzed Cascade Intramolecular Cyclization and Allylation of Enynoates with Allylic Alcohols.

A Pd(II)-catalyzed mild and highly regioselective 6- endo cyclization/allylation reaction of enynoates with simple allylic alcohols has been developed. Under mild reaction conditions, the vinyl palladium species generated in situ after cyclization could insert C-C double bond of allylic alcohol through cross-coupling reaction and lead to the formation of allyl pyrone via β-OH elimination. This cascade cross-coupling reaction represents a direct and atom economic methodology for the construction of novel allyl pyrones in moderate to good yields.

Niobium-Catalyzed Intramolecular Addition of O-H and N-H Bonds to Alkenes: A Tool for Hydrofunctionalization.

A convenient, versatile, and easy to handle intramolecular hydrofunctionalization of alkenes (C-O and C-N bonds formation) is reported using a novel niobium-based catalytic system. This atom economic and eco-friendly methodology provides an additional synthetic tool for the straightforward formation of valuable building blocks enabling molecular complexity. Various pyran, furan, pyrrolidine, piperidine, lactone, and lactam derivatives as well as spirocyclic compounds are produced in high yields and selectivities.

Tandem Addition of Phosphite Nucleophiles Across Unsaturated Nitrogen-Containing Systems: Mechanistic Insights on Regioselectivity

The addition of phosphite nucleophiles across linear unsaturated imines is a powerful and atom-economical methodology for the synthesis of aminophosphonates. These products are of interest from both a biological and a synthetic point of view: they act as amino acid transition state analogs and Horner-Wadsworth-Emmons reagents, respectively. In this work the reaction between dialkyl trimethylsilyl phosphites and α,β,γ,δ-diunsaturated imines was evaluated as a continuation of our previous efforts in the field. As such, the first conjugate 1,6-addition of a phosphite nucleophile across a linear unsaturated N-containing system is reported herein. Theoretical calculations were performed to rationalize the observed regioselectivites and to shed light on the proposed mechanism.

An air-stable half-sandwich Ru(II) complex as an efficient catalyst for [3+2] annulation of 2-arylcyclo-2-enones with alkynes.

An air-stable half-sandwich ruthenium(II) complex, [Ru(p-cymene)(MeCN)3](SbF6)2, was synthesized and characterized. It exhibited unique catalytic ability in a [3+2] annulation reaction of 2-arylcyclo-2-enones with internal alkynes via C(sp(2))-H/alkene functionalization, which offered a rapid and atom-economical methodology to construct various synthetically challenging spiro carbocyclic indenes bearing a quaternary carbon.

The synthesis of sterically hindered amines by a direct reductive amination of ketones

An atom-economical methodology for the synthesis of sterically hindered tertiary amines was developed, which is based on complementary Rh- and Ru-catalyzed direct reductive amination of ketones with primary and secondary amines using carbon monoxide as a deoxygenating agent.

The synthesis of C2 symmetry diesters of (3R,4R)-TTFOL through a green and stereoselective (2R,3R)-TADDOL rearrangement

An efficient, green, and atom economic methodology for the stereoselective synthesis of C2 symmetry (3R,4R)-TTFOL diester derivatives has been developed. The procedure occurs through a (2R,3R)-TADDOL dioxolane cleavage and rearrangement under mild conditions by its reaction with a carboxylic acid in the presence of TFAA/H3PO4 without the need for an inert atmosphere to give generally high yields.

One-Pot Synthesis of Propargylamines Using Ag(I)-Exchanged K10 Montmorillonite Clay as Reusable Catalyst in Water

Ag(I)-exchanged K10 montmorillonite clay is found to be an efficient heterogeneous catalyst for the one-pot three-component coupling of terminal alkynes, amines, and aqueous formaldehyde (A3 coupling) to yield corresponding propargylamines in water. In all the cases, quantitative yields of the desired products are obtained. The catalyst is recovered by filtration and reused several times with only a slight decrease in its catalytic activity. This atom economical methodology does not require an additional co-catalyst or activator, and water is the only byproduct. Interestingly, the reaction can also be performed under solvent-free conditions in the case of aromatic and aliphatic aldehydes, along with formaldehyde, affording propargylamine derivatives in higher yields. A tentative mechanism is also proposed for this transformation.

Catalytic C–H Activation of Arylacetylenes: A Fast Assembly of 3-(Arylethynyl)-3-hydroxyindolin-2-ones Using CuI/DBU

A highly efficient and atom-economic methodology has been developed for the synthesis of 3-(arylethynyl)-3-hydroxyindolin-2-ones from isatins by C–H activation of arylacetylenes using a catalytic quantity of copper(I) iodide (5 mol%) and DBU (20 mol%) at 25 °C, affording the products in excellent yields in very short reaction time (5 min).

ChemInform Abstract: Microwave‐Assisted Synthesis of 3‐Methyl‐1‐phenylchromeno[4,3‐c]pyrazol‐4(1H)‐ones under Solvent‐Free Conditions.

AbstractCompared with existing methods, this novel green and atom economical methodology for the synthesis of chromenopyrazolones (II) and (IV) affords the target products in higher yields and shorter reaction times.

Coupling of Methyl Ketones and Primary or Secondary Amines Leading to α-Ketoamides

A metal-free oxidative coupling of methyl ketones and primary or secondary amines to α-ketoamides has been developed. Four intermediates, α-iodoketone, α-aminoketone, iminium intermediate, and α-hydroxy amine have been identified through a series of control experiments. The atom-economic methodology can be scaled-up, tolerates a variety of functional groups, and is operationally simple.

An ionic liquid {[secbmim]+ Br¯} as a “dual reagent catalyst” for the multicomponent synthesis of (quinolinyl- and isoquinolinyl- amino) alkylnaphthols, their bis- analogs and a facile route to naphthoxazines

An atom-economic methodology has been developed for the multi- component one–pot synthesis of (quinolinyl- and isoquinolinyl- amino) alkyl naphthols and their bis- analogs employing the ionic liquid {[ sec bmim] + Br¯} as a “dual reagent catalysis” at 25 oC. The present approach possesses several advantages such as excellent yields, lower reaction times, mild reaction conditions, recyclability and very easy purification processes. The methodology has been further extended towards the facile synthesis of naphthoxazines in very good yields employing formaldehyde in place of aromatic aldehydes.