Atom-economic Reaction Research Articles

Selective Synthesis of Pyrano[3,2-b]indoles or Cyclopenta[b]indoles Tethered with Medium-Sized Rings via Cascade C-C σ-Bond Cleavage and C-H Functionalization.

Highly atom-economical tandem reactions have been developed for the synthesis of pyrano[3,2-b]indoles or cyclopenta[b]indoles tethered with 7-, 8-, or 9-membered rings. These reactions first undergo a carbon-carbon σ-bond cleavage reaction of cyclic β-ketoesters. Next, in the presence of CuCl2 and Ag2CO3, intramolecular O-H/C-H coupling occurs to give pyrano[3,2-b]indoles. This is the first example for capture of the enoloxyl radical of the intramolecular C-O bond formation reaction, whereas C3 nucleophilic addition afforded cyclopenta[b]indoles using TsOH·H2O.

Toward Replacing Ethylene Oxide in a Sustainable World: Glycolaldehyde as a Bio-Based C2 Platform Molecule.

Fossil-based platform molecules such as ethylene and ethylene oxide currently serve as the primary feedstock for the C2 -based chemical industry. However, in the search for a more sustainable chemical industry, fossil-based resources may preferentially be replaced by renewable alternatives, provided there is realistic economic feasibility. This Review compares and critically discusses several production routes toward bio-based structural analogues of ethylene oxide and the required adaptations for their implementation in state-of-the-art C2 -based chemical processes. For example, glycolaldehyde, a structural analogue obtainable from carbohydrates by atom-economic retro-aldol reactions, may replace ethylene oxide's leading role. This alternative chemical route may not only allow the carbon footprint of conventional chemicals production to be lowered, but the introduction of a bio-based pathway may also contribute to safer production processes. Where possible, challenges, drawbacks, and prospects are highlighted.

Click-Grafting of Cardanol onto Mesoporous Silica/Silver Janus Particles for Enhanced Hemostatic and Antibacterial Performance

Janus particles with obvious chemical compartition can perform their functions independently, so they have attracted much attention in biomedical materials. Herein, a mesoporous silica/silver Janus nanoparticle modified with cardanol (C-MSN@Ag) was designed and synthesized via redox and click chemical reactions and was further evaluated as a highly efficient hemostatic dressing. This Janus structure endowed C-MSN@Ag with both prominent hemostatic and antibacterial performance. The hemostatic time of C-MSN@Ag on rat liver laceration was up to 40% shorter than that of MSN and MSN@Ag because of adhesion of phenolic compounds on the tissue and the blocking effect of the hydrophobic alkyl chains from cardanol. Besides, C-MSN@Ag could promote coagulation by forming a three-dimensional network with fibrin more quickly than MSN and MSN@Ag. Additionally, due to the released silver ions and phenolic hydroxyl groups of cardanol, C-MSN@Ag exhibited a broad-spectrum antibacterial rate (∼99%) against both Escherichia coli and Staphylococcus aureus. C-MSN@Ag also possessed non-cytotoxicity. This work not only provides a way for the fabrication of silica-based Janus hemostatic agents by the atom-economical click reaction but also gives a direction for the application of the sustainable naturally occurring cardanol.

An efficient and recyclable AgNO3/ionic liquid system catalyzed atmospheric CO2 utilization: Simultaneous synthesis of 2-oxazolidinones and α-hydroxyl ketones

Oxazolidinones and α-hydroxyl ketones are two series of fine chemicals that have been generally utilized in biological, pharmaceutical, and synthetic chemistry. Herein, a AgNO3/ionic liquid (IL) catalytic system was developed for the simultaneous synthesis of these compounds through the atom-economical three-component reactions of propargyl alcohols, 2-aminoethanols, and CO2. Notably, this system behaved excellent catalytic activity with the lowermost metal loading of 0.25 mol%. Meanwhile, it is the first reported metal-catalyzed system that could efficiently work under atmospheric CO2 pressure and be recycled at least five times. Evaluation of the green metrics proved the AgNO3/IL-catalyzed processes to be relatively more sustainable and greener than the other Ag-catalyzed examples. Further mechanistic investigations revealed the derivative active species of N-heterocyclic carbene (NHC) silver complexes and CO2 adducts generated during the process. Subsequently, their reactivity in this reaction was assessed for the first time, which was finally identified as beneficial for the catalytic activity.

Cyclative MCRs of Azines and Azinium Salts

Since the first discovery by Huigsen and co‐workers fifty years ago, a wide range of organic reactions have taken place through the intermediary of the dipolar/zwitterionic species produced by the combination of a neutral nucleophile and an unsaturated electrophile. Nucleophilic initiators including heterocycles may react or play a mediating role based on their nucleophilic nature and reaction conditions. This review highlights the recent developments of the cyclization chemistry of heterocycles using multicomponent reactions (MCRs) – including unusual dearomatizative examples. Heterocycles as very common structural units can often be found in natural and pharmaceutical products. MCRs are environmentally benign and highly atom economic reactions. Their application in the synthesis of biologically active molecules may provide alternatives for the greener synthesis of drugs lowering the carbon footprint of pharmaceutical industries.

An efficient and green method to prepare bis-α-hydroxy phosphonates using triethylamine as catalyst

An efficient, convenient and environmentally friendly method for the synthesis of bis-α-hydroxy phosphonates via a perfectly atom economical Pudovik reaction is described. Using 5 mol% of triethylamine as a catalyst, a series of aromatic/heteroaromatic dialdehydes reacts with dialkyl phosphites to afford the corresponding bis-α-hydroxy phosphonates, particularly the bio-mass based ones, under solvent-free conditions or in a minimum amount of tetrahydrofuran at room temperature with moderate to excellent yields (52–95%).

Atom-economic synthesis of Magnéli phase Ti4O7 microspheres for improved sulfur cathodes for Li–S batteries

Magnéli phase Ti 4 O 7 with high electronic conductivity showed great promise as an inactive component of S cathodes that mitigates some intrinsic limitations of ultra-lightweight lithium-sulfur batteries (LSBs) based on low-cost, high specific capacity and largely environmentally benign sulfur (S). Here we report for the first time a straightforward and economic approach to synthesize mesoporous Magnéli phase Ti 4 O 7 microspheres by simply heating a mixture of elemental titanium and TiO 2 in argon. The phase-controlled method utilizes the mildest synthesis conditions to-date with lower temperature and exclusion of flammable hydrogen gas traditionally used, and also avoids generation of exhaust greenhouse gases during carbothermal synthesis using sacrificial polymers. The produced S/Ti 4 O 7 composite cathode with 70 wt% S loading efficiently mitigated the shuttle effect by both chemical adsorption and physical trapping of polysulfides. Consequently, this cathode showed high (88%) first cycle columbic efficiency, excellent cycling stability (capacity decay of ~ 0.09% per cycle for 500 cycles), small polarization and good rate performance, significantly exceeding the performance of S/TiO 2 and S/activated carbon cathodes with similar/smaller S loading. We anticipate that this work will provide new avenues for more economic and environmentally friendly synthesis of various Magnéli phase metal oxides, and their exploration in LSBs and other fields. • Precise Magnéli Ti 4 O 7 microsphere synthesis by atom-economic and safe comproportionation reaction. • New mechanistic insights in the prevention of LiPS dissolution. • Outstanding performance of the Ti 4 O 7 /S cathodes with high S loading (~ 70%). • Generality of the synthesis is shown for other Magnéli phases.

Organocatalytic Asymmetric Tandem Cyclization/Michael Addition via Oxazol-5(2H)-One Formation: Access to Perfluoroalkyl-Containing N,O-Acetal Derivatives.

Herein, we report a convenient organocatalytic asymmetric tandem cyclization/Michael addition protocol for the synthesis of diastereomerically pure and highly enantioenriched perfluoroalkyl-containing N,O-acetal derivatives starting from racemic N-perfluoroacyl amino acids under mild conditions. This efficient atom economic reaction leads to highly enantioselective and diastereoselective construction of N,O-acetal derivatives containing oxazolone and perfluoroalkyl moieties containing vicinal quaternary and tertiary stereocenters (up to 97% yield, up to 96% ee, and up to >20:1 dr).

The Application of Biomass-Based Catalytic Materials in the Synthesis of Cyclic Carbonates from CO2 and Epoxides.

The synthesis of cyclic carbonates from carbon dioxide (CO2) and epoxides is a 100% atom economical reaction and an attractive pathway for CO2 utilisation. Because CO2 is a thermodynamically stable molecule, the use of catalysts is mandatory in reducing the activation energy of the CO2 conversion. Considering environmental compatibility and the high-efficiency catalytic conversion of CO2, there is the strong need to develop green catalysts. Biomass-based catalysts, a type of renewable resource, have attracted considerable attention due to their unique properties—non-toxic, low-cost, pollution-free, etc. In this review, recent advances in the development of biomass-based catalysts for the synthesis of cyclic carbonates by CO2 and epoxides coupling are summarized and discussed in detail. The effect of biomass-based catalysts, functional groups, reaction conditions, and co-catalysts on the catalytic efficiency and selectivity of synthesizing cyclic carbonates process is discussed. We intend to provide a comprehensive understanding of recent experimental and theoretical progress of CO2 and epoxides coupling reaction and pave the way for both CO2 conversion and biomass unitization.

Catch It If You Can: Copper-Catalyzed (Transfer) Hydrogenation Reactions and Coupling Reactions by Intercepting Reactive Intermediates Thereof

The key reactive intermediate of copper(I)-catalyzed alkyne semihydrogenations is a vinylcopper(I) complex. This intermediate can be exploited as a starting point for a variety of trapping reactions. In this manner, an alkyne semihydrogenation can be turned into a dihydrogen­-mediated coupling reaction. Therefore, the development of copper-catalyzed (transfer) hydrogenation reactions is closely intertwined with the corresponding reductive trapping reactions. This short review highlights and conceptualizes the results in this area so far, with H2-mediated carbon–carbon and carbon–heteroatom bond-forming reactions emerging under both a transfer hydrogenation setting as well as with the direct use of H2. In all cases, highly selective catalysts are required that give rise to atom-economic multicomponent coupling reactions with rapidly rising molecular complexity. The coupling reactions are put into perspective by presenting the corresponding (transfer) hydrogenation processes first.1 Introduction: H2-Mediated C–C Bond-Forming Reactions2 Accessing Copper(I) Hydride Complexes as Key Reagents for Coupling Reactions; Requirements for Successful Trapping Reactions3 Homogeneous Copper-Catalyzed Transfer Hydrogenations4 Trapping of Reactive Intermediates of Alkyne Transfer Semi­hydrogenation Reactions: First Steps Towards Hydrogenative Alkyne Functionalizations5 Copper(I)-Catalyzed Alkyne Semihydrogenations6 Copper(I)-Catalyzed H2-Mediated Alkyne Functionalizations; Trapping of Reactive Intermediates from Catalytic Hydrogenations6.1 A Detour: Copper(I)-Catalyzed Allylic Reductions, Catalytic Generation of Hydride Nucleophiles from H26.2 Trapping with Allylic Electrophiles: A Copper(I)-Catalyzed Hydro­allylation Reaction of Alkynes6.3 Trapping with Aryl Iodides7 Conclusion

Computational study on atom-economic alkyne hydrotelluration reaction using benchmarked ECP for Te

Geometry and energy calibration studies are done for arriving at a proper ECP for tellurium containing compounds. Among the various d-function included ECPs cc-pwCVTZ-PP and def2-TZVP give more reliable results. Non-catalytic and base/radical initiated hydrotelluration reactions are computationally studied using the calibrated def2-TZVP, with a special focus on the regio-and stereoselective formation of vinyl tellurides. The explored gas phase reaction mechanism indicates the addition of tellurol to unsaturated carbon-carbon triple bond via a concerted transition structure. Regioselectivity has been noticeably realized in presence of both base and radical mediated hydrotelluration leading to Markovnikov and anti-Markovnikov product respectively.

Frontispiece: Exceptional Substrate Diversity in Oxygenation Reactions Catalyzed by a Bis(μ‐oxo) Copper Complex

The tyrosinase-like activity of a new bioinspired bis(μ-oxo) dicopper(III) catalyst was investigated herein. The hybrid guanidine-stabilized catalyst revealed a remarkable oxygenation activity on diverse phenolic substrate classes, products of which were consistently predicted by DFT calculations. The selective C−H activation of mono- and bicyclic substrates provides a new benchmark to future developments on tyrosinase model systems on the route to atom-economic oxygen-transfer reactions. More information can be found in the Communication by S. Herres-Pawlis et al. on page 7556 ff.

Divergent Synthesis of Five-Membered Nitrogen Heterocycles via Cascade Reactions of 4-Arylfuroxans

A novel method for the synthesis of a diverse series of functionally substituted five-membered heterocyclic compounds via atom-economic, regio-, and diastereoselective one-pot reaction cascade was developed. This approach involves a ring opening in 4-arylfuroxans to α-oximinoarylacetonitrile oxides followed by [3+2] cycloaddition to various dipolarophiles to afford multisubstituted isoxazoles and isoxazolines. Subsequent azole–azole rearrangement of (oximino)isoxazolines/-isoxazoles, which can be conducted in a one-pot manner, results into functionally substituted furazans formation. The developed protocol is operationally simple, proceeds in mild conditions and with high yields of target heterocyclic systems. Overall, this study represents a new mode of isoxazole and 1,2,5-oxadiazole functionalization strategy, which is useful in medicinal and materials chemistry.

Organocatalytic Synthesis of Highly Functionalized Heterocycles by Enantioselective aza-Morita-Baylis-Hillman-Type Domino Reactions.

Organocatalytic enantioselective domino reactions are an extremely attractive methodology, as their use enables the construction of complex chiral skeletons from readily available starting materials in two or more steps by a single operation under mild reaction conditions. Thus, these reactions can save both the quantity of chemicals and length of time typically required for the isolation and/or purification of synthetic intermediates. Additionally, no metal contamination of the products occurs, given that organocatalysts include no expensive or toxic metals. The aza-Morita-Baylis-Hillman (aza-MBH) reaction is an atom-economical carbon-carbon bond-forming reaction between α,β-unsaturated carbonyl compounds and imines mediated by Lewis base (LB) catalysts, such as nucleophilic phosphines and amines. aza-MBH products are functionalized chiral β-amino acid derivatives that are highly valuable as pharmaceutical raw materials. Although various enantioselective aza-MBH processes have been investigated, very few studies of aza-MBH-type domino reactions have been reported due to the complexity of the aza-MBH process, which involves a Michael/Mannich/H-transfer/β-elimination sequence. Accordingly, in this review article, our recent efforts in the development of enantioselective domino reactions initiated by MBH processes are described. In the domino reactions, chiral organocatalysts bearing Brønsted acid (BA) and/or LB units impart synergistic activation to substrates, leading to the easy synthesis of highly functionalized heterocycles (some of which have tetrasubstituted and/or quaternary carbon stereocenters) in high yield and enantioselectivity.

Palladium-Catalyzed Formal (4+2) Cycloaddition between Alkyl Amides and Dienes Initiated by the Activation of C(sp3)–H Bonds

We report a formal (4+2) cycloaddition between alkyl-nosylamides and dienes enabled by a palladium-catalyzed activation of C(sp3)–H bonds beta to the amide group. This atom economical reaction, whi...

Transition-metal and base-free thioannulation of propynamides with sodium sulfide and dichloromethane for the selective synthesis of 1,3-thiazin-4-ones and thiazolidine-4-ones

A thioannulation of propynamides with sodium sulfide and CH2Cl2 in the absence of transition-metal and base has been established. This one-pot tandem reaction provides a facile and efficient method for the selective synthesis of 1,3-thiazide-4-ones or thiazolidine-4-ones through constructing both C–N and C–S bonds. The atom-economic reaction features mild conditions and good functional group tolerance, as well as the use of cheap, safe and odorless sulfur source.

Ligand Free One-Pot Synthesis of Pyrano[2,3-c]pyrazoles in Water Extract of Banana Peel (WEB): A Green Chemistry Approach.

Here, we have developed a novel, simple, efficient, and green protocol for one-pot synthesis of pyrano[2,3-c]pyrazole using arylidene malononitrile and pyrazolone in Water Extract of Banana Peels (WEB) as a reaction medium at room temperature (r.t.). This is a green and general synthetic protocol without utilization of any toxic organic solvent, ligand, base that could be applicable for the wide substrate scope in good to excellent yields. This protocol has various advantages such as fast reactions, eco-friendly reaction conditions, easy isolation of the product without using column chromatography. The green chemistry matrices calculation like atom economy reaction, environmental factor, as well as process mass intensity indicates the eco-friendly nature of the protocol.

Transition-Metal-Free Synthesis of Pyridine Derivatives by Thermal Cyclization of N-Propargyl Enamines

A transition-metal-free synthesis of pyridine derivatives by 6-endo-dig cyclization of N-propargyl enamines was developed. This method is environmentally friendly and is a high atom economy reaction that is easily accessed to provide pyridine derivatives in moderate to good yield by heating N-propargyl enamines in solvent without additives. The total synthesis of onychine was achieved in 51% yield in only two steps by using this method.

H-Pyrr][HSO4] as an Efficient Ionic Liquid Catalyst for the Synthesis of Xanthenes, Tetraketones, and Triazolo[2,1-b]quinazolinones

Pyrrolidin-1-ium hydrogen sulfate ([H-Pyrr][HSO4]) was prepared by a simple and atom-economic neutralization reaction of sulfuric acid and pyrrolidine. This reagent can be used as an easily available, cheap, recyclable, and environmentally benign catalyst for the promotion of the synthesis of 1,8-dioxo-octahydro-xanthenes, tetraketones, and triazolo[2,1-b]quinazolinone derivatives. Easy preparation of the catalyst, simple work-up procedure, green process, high yields, and short reaction times are the most important advantages of this method.

Atom economical coupling of benzophenone and N-heterocyclic aromatics with SmI2.

The use of stoechiometric SmI2 in combination with benzophenone and N-heterocyclic aromatics such as bipyridine, phenanthroline and pyridine allows the direct ortho-coupling of both partners in an atom economical reaction free of any other coupling additives. The transformation was investigated by 1H NMR, X-ray studies and theoretical calculations providing reaction intermediates and the reaction mechanism.