Domino Process Research Articles

Silver(I)-Mediated Cascade Reaction of 2-(1-Alkynyl)-2-alken-1-ones with 2-Naphthols

An efficient cascade reaction of 2-(1-alkynyl)-2-alken-1-ones with 2-naphthols promoted by silver trifluoroacetate is disclosed, providing an expeditious access to 1,2-dihydronaphtho[2,1-b]furans with moderate to good yields. This domino process involves highly regio- and diastereoselective sequential cyclization/nucleophilic addition/oxidative ring opening/oxa-Michael addition reactions to construct three new chemical bonds and one new five-membered ring. A gram-scale experiment and the preliminary results to develop an asymmetric variant are also presented to show the practicality and potential of the current reaction.

4-Amino-1,2,4-triazoles-3-thiones and 1,3,4-oxadiazoles-2-thiones·palladium(II) recoverable complexes as catalysts in the sustainable Suzuki-Miyaura cross-coupling reaction

The Suzuki-Miyaura cross-coupling reaction using 4-amino-1,2,4-triazoles and 1,3,4-oxadiazoles-2-thiones·palladium (II) is studied. The reaction is optimized and the most appropriate catalytic complex is tested with several aryl halides, boronic acids in an environmentally benign solvent system (H2O/EtOH). The recovery of the catalytic species is also surveyed because of the nature of the employed solvent. A domino process is efficiently carried out following the standard conditions. Several surface parameters of the ligands are analyzed and the resulting values are extrapolated to the insoluble palladium catalyst.

Pd-Catalyzed Domino Reactions Involving Alkenes To Access Substituted Indole Derivatives

Palladium-catalyzed domino reactions are advanced tools in achieving various nitrogen-containing heterocycles in an efficient and economical manner due to the reduced number of steps in the process. This review highlights recent advances in domino processes aimed at the synthesis of indole derivatives and polycyclic systems containing the indole nucleus in intra/intra- or intra/intermolecular reactions. In particular, we consider domino processes that involve a double bond in a step of the sequence, which allow the issue of regioselectivity in the cyclization to be faced and overcome. The different sections in this review focus on the synthesis of the indole nucleus and functionalization of the scaffold starting from different substrates that have been identified as activated starting materials, which involve a halogenated moiety or unactivated unsaturated systems. In the former case, the reaction is under Pd(0) catalysis, and in the second case a Pd(II) catalytic species is required and then an oxidant is necessary to reconvert the Pd(0) into the active Pd(II) species. On the other hand, the second method has the advantage that it uses easy available and inexpensive substrates.1 Introduction2 Indole Scaffold Synthesis2.1 Activated Substrates2.2 Unactivated Substrates3 Functionalization of Indole Scaffold3.1 Activated Substrates3.2 Unactivated Substrates4 Conclusions

(Invited) Heterogenized Molecular Catalyst Materials for Electrochemical Carbon Dioxide Conversion

Sustainable energy utilization and carbon emission reduction are critical challenges for the world. Solving these challenges requires precise control of many important chemical reactions with sluggish kinetics and myriad possible reaction pathways and associated products. There is a critical need for selective, active, durable and low-cost catalysts. This talk presents our research efforts aimed at bridging the gap between homogenous catalysis and heterogeneous catalysis to realize materials with new or improved electrocatalytic properties for the carbon dioxide reduction reactions. We have developed heterogenized metal-complex electrocatalysts allowing for mechanism-based optimization at the molecular level. We have discovered interesting phenomena including ligand-mediated electron transfer, beyond two-electron reduction via a domino process, and reversible restructuring under reaction conditions. We have also designed reactors to enhance electrochemical performance, study surface/interface phenomena, and perform thermodynamically challenging reactions.

Graphene Layers Functionalized with A Janus Pyrrole-Based Compound in Natural Rubber Nanocomposites with Improved Ultimate and Fracture Properties.

The ultimate properties and resistance to fracture of nanocomposites based on poly(1,4-cis-isoprene) from Hevea Brasiliensis (natural rubber, NR) and a high surface area nanosized graphite (HSAG) were improved by using HSAG functionalized with 2-(2,5-dimethyl-1H-pyrrol-1-yl)propane-1,3-diol (serinol pyrrole) (HSAG-SP). The functionalization reaction occurred through a domino process, by simply mixing HSAG and serinol pyrrole and heating at 180 °C. The polarity of HSAG-SP allowed its dispersion in NR latex and the isolation of NR/HSAG-SP masterbatches via coagulation. Nanocomposites, based either on pristine HSAG or on HSAG-SP, were prepared through traditional melt blending and cured with a sulphur-based system. The samples containing HSAG-SP revealed ultimate dispersion of the graphitic filler with smaller aggregates and higher amounts of few layers stacks and isolated layers, as revealed by transmission electron microscopy. With HSAG-SP, better stress and elongation at break and higher fracture resistance were obtained. Indeed, in the case of HSAG-SP-based composites, fracture occurred at larger deformation and with higher values of load and, at the highest filler content (24 phr), deviation of fracture propagation was observed. These results have been obtained with a moderate functionalization of the graphene layers (about 5%) and normal lab facilities. This work reveals a simple and scalable way to prepare tougher NR-based nanocomposites and indicates that the dispersion of a graphitic material in a rubber matrix can be improved without using an extra-amount of mechanical energy, just by modifying the chemical nature of the graphitic material through a sustainable process, avoiding the traditional complex approach, which implies oxidation to graphite oxide and subsequent partial reduction.

Green Synthesis of Poly‐Substituted Pyrano[4,3‐b]quinoline‐1,9‐(5H)‐dione Derivatives Using Solid Acid as Catalyst in Water

AbstractA series of new pyrano[4,3‐b]quinoline‐1,9(5H)‐dione derivatives were synthesized via one‐pot three‐component reaction using 6‐methyl‐4‐(arylamino)‐2H‐pyran‐2‐ones, aldehydes, and 1,3‐cyclohexanediones as substrates. The application of 4‐methylbenzenesulfonyl chloride activated the hydroxyl group of pyranone and avoided the forming of ring opening product. The reaction proceeds smoothly and gives biological and pharmacological active substituted pyrano[4,3‐b]quinoline‐1,9(5H)‐dione derivatives with good to excellent yields under green conditions. A plausible mechanism for the domino process is proposed.

Synthesis of Novel Spiro[chromene-4,3'-indolines] and Spiro(indoline-3,4'-pyrano[3,2-h]quinolines)

The condensation of 1-alkylisatines with malononitrile and 8-hydroxyquinoline or 5,5-dimethyl-cyclohexane-1,3-dione in the presence of an aqueous solution of trimethylamine proceeds regioselectively as a one-pot three-component domino process to form spiro[chromene-4,3'-indoline] and spiro(indoline-3,4'-pyrano[3,2-h]quinoline).

Hexamethylphosphanetriamine‐mediated aziridination of imines with alpha‐ketoesters: A molecular electron density theory study

AbstractThe highly trans‐stereoselective reaction of oxyphosphonium enolate (OPE) with N‐benzylidene‐4‐methoxybenzenesulfonamide (N‐BMS) in toluene, at room temperature leading to trans‐aziridine‐2‐carboxylate (trans‐Az 3), was theoretically studied using molecular electron density theory (MEDT) at the B3LYP/6‐31G(d) computational level to shed light on the energy transformation, selectivities, and mechanistic aspects. This domino process is initialized by adding of N,N,N′,N′,N″,N″‐hexamethylphosphanetriamine (HMPT) to methyl benzoylformate to generate OPE. Subsequently, nucleophilic addition of OPE to the C–N double bond in N‐BMS leads to the intermediate IN‐Ta. Finally, trans‐Az 3 is formed through a 3‐exo‐tet ring closure step as a result of the nucleophilic attack of the negatively charged nitrogen atom on the carbon atom bearing –OP (NMe2)3 in IN‐Ta. Analysis of the relative Gibbs free energies shows that the ring closure step is the rate‐determining step. By an investigation of the conceptual density functional theory reactivity indices, OPE and N‐BMS are classified as a strong nucleophilic and as a strong electrophilic species, respectively, which indicates that the additional step of OPE to N‐BMS should display a high‐polar character. An analysis of the calculated electrophilic and nucleophilic Parr functions at the reactive sites of reagents clarifies the regioselectivity observed experimentally along the C1–C2 bond formation process.

Selenium chlorides in the domino process of the regiospecific allyl chlorination of betulin and diacetylbetulin

ABSTRACTThe interaction of betulin and diacetylbetulin with selenium chlorides occurs regiospecific with allylic chlorination of the substrate. Selenium chlorides are obtained by chlorination of selenium with sulfuryl chloride in the form of a mixture of SeCl2 and Se2Cl2. An intermediate product of the domino process, unsaturated allylic structure chloroselenide, was detected by 77Se and 1H NMR. The rate of conversion of selenide to allyl chloride was determined. According to the results of quantum-chemical calculations, in the reactions of betulin and diacetylbetulin with both SeCl2 and Se2Cl2, intermediates of the episelenuran type are formed in the first stage. Further, these intermediates are converted to unsaturated selenium chlorides by elimination of HCl. According to the calculation results, the final stage of the domino process – the formation of allyl chlorides is realized due to the catalytic action of SeCl2 in the elimination of selenium.

Photo-Biocatalytic Cascades for the Synthesis of Volatile Sulfur Compounds and Chemical Building Blocks

Biocatalysis is a branch of catalysis that exploits enzymes to perform highly stereoselective chemical transformations under mild and sustainable conditions. This Synpact highlights how biocatalysis can be used in the synthesis of chiral 1,3-mercaptoalkanols, an important class of compounds responsible for the flavours and aromas of many foods and beverages. The identification of two ketoreductase (KRED) enzymes able to reduce prochiral ketone precursors enantioselectively to 1,3-mercaptoalkanols bearing a C–O stereocentre is presented. In addition, the combination of a photocatalytic thia-Michael reaction to access prochiral ketones with subsequent KRED-biocatalysed reduction in a one-pot cascade is presented. Photo-biocatalysed cascades represent one of the new and most intriguing challenges in synthetic chemistry, because the combination of different catalytic methodologies in domino processes offers unique opportunities to outperform sequential reactions with a high degree of selectivity and the avoidance of the need to isolate reaction intermediates.1 Introduction2 Biocatalytic Synthesis of 1,3-Mercaptoalkanols3 Photo-Biocatalytic Synthesis of 1,3-Mercaptoalkanols4 Photo-Biocatalysed Cascade Reactions5 Conclusions

Synthesis of 2-Imidazolines via Palladium-Catalyzed Cyclization Reaction of 2,3-Allenyl Amines and Aryl Iodides

An effective method for the synthesis of polysubstituted 2-imidazoline derivatives via palladium-catalyzed cyclization of 2,3-allenyl amines with aryl iodides is described. This pure domino process allows the formation of new carbon–carbon and carbon–nitrogen bonds in a single synthetic operation.

Three Ways Aliphatic Aldehydes React with Nonstabilized Azomethine Ylides

Aliphatic aldehydes readily react with nonstabilized azomethine ylides in one of the three ways to give oxazolidines, pyrrolidines, or Mannich bases, depending on the structure of the starting compound and the reaction conditions. The use of N-(methoxymethyl)-N-[(trimethylsilyl)methyl]benzylamine in DMF provided 5-alkyloxazolidines in 40–97% yields. On the other hand, three-component reactions of aliphatic aldehydes bearing one α-hydrogen with N-methyl(benzyl)glycine and formaldehyde gives Mannich bases in yields of 47–98%. A similar reaction of aldehydes bearing branched alkyl groups and two hydrogen atoms at the α-position proceeds as a domino process that gives 3-alkyl-3-formylpyrrolidines in yields of 34–93%.

Synthesis of 2,1-Benzoisoxazole-Containing 1,2,3-Triazoles through Copper-Catalyzed Three-Component Domino Reactions of o-Bromoacetophenones, Aldehydes, and Sodium Azide

We herein describe an efficient copper-catalyzed three-component domino protocol used to prepare 2,1-benzoisoxazole-containing 1,2,3-triazoles from commercially available o-bromoacetophenones, aldehydes, and sodium azide. This domino process involves Aldol condensation, copper-catalyzed azide-chalcone oxidative cyclization, 1,2,3-triazole-assisted azidation, and denitrogenative cyclization sequences. The formed compounds could be considered as benzo[c]isoxazole-functionalized combretastatin A-4 triazole analogues, which might be potential applications in the discovery of a new anticarcinogen.

Cooperative Palladium and Copper Catalysis: One‐pot Synthesis of Diamino‐Substituted Naphthalenes from Aryl Halides, 1,4‐Bis(trimethylsilyl)butadiyne and Amines

AbstractA one‐pot method for the preparation of diamino‐substituted naphthalene derivatives from easily available starting materials aryl halides, 1,4‐bis(trimethylsilyl)butadiyne and amines is developed. Two C−N bonds, three C−C bonds and one aromatic ring are formed in this domino process. This transformation is achieved by the cooperative catalysis of Pd(OAc)2, Cu(Xantphos)I and Cu(OTf)2. A possible double Sonogashira coupling/hydroamination/ benzannulation reaction route is proposed.

A general method for site-selective Csp3-S bond formation via cooperative catalysis.

Herein, we report a copper-catalysed site-selective thiolation of Csp3–H bonds of aliphatic amines. The method features a broad substrate scope and good functional group compatibility. Primary, secondary, and tertiary C–H bonds can be converted into C–S bonds with a high efficiency. The late-stage modification of biologically active compounds by this method was also demonstrated. Furthermore, the one-pot preparation of pyrrolidine or piperidine compounds via a domino process was achieved.

A domino annulation approach to 3,4-diacylpyrrolo[1,2-a]pyrazines: decoration of pyrazine units.

A new one-pot, sequential three-component access to 3,4-diacylpyrrolo[1,2-a]pyrazine was achieved from the reaction of an α-haloketone, azide, and N-substituted pyrrole-2-carboxaldehyde under mild reaction conditions, through which a polysubstitution pattern on the pyrazine moiety of the scaffold was realized. The formation of multiple bonds (one C-C and two C-N) was enabled by this domino process involving the in situ generation of α-iminoketones, intermolecular Mannich reaction, intramolecular imine formation, and aromatization. Construction of the relevant 3,4-diacylpyrazino[1,2-a]indole and further expansion of this chemical space via synthetic elaboration of the resulting products were demonstrated as well. Preliminary biological screening of the synthesized derivatives against oral adenosquamous carcinoma cells (CAL-27) and triple negative human breast cancer cells (MDA-MB-231) led us to identify a potent hit compound (7o) having ∼3 times stronger in vitro anticancer activity than that of the anticancer agent, capecitabine.

Solvent-free and montmorillonite K10-catalyzed domino reactions for the synthesis of pyrazoles with alkynylester as a dual synthon

A highly regioselective, solvent-free and montmorillonite K10 clay-catalyzed domino process with an unprecedented C–C bond formation reaction is described for the synthesis of new class of tri-substituted and di-substituted pyrazole derivatives.

Copper-catalyzed double C-S bond formation for the synthesis of 2-acyldihydrobenzo[b]thiophenes and 2-acylbenzo[b]thiophenes.

An efficient domino process is developed for the synthesis of diversely substituted 2,3-dihydrobenzo[b]thiophenes from 2-iodoketones using a Cu-catalyst and easily available xanthate as a sulfur surrogate in good yields. This domino method has been expanded for the synthesis of 2-acylbenzo[b]thiophenes using in situ generated iodine (I2) from by-product KI in high yields. Treatment of xanthate with the copper(ii)-catalyst reduced it to a Cu(i)-catalyst, which initiates the catalytic cycle. A possible mechanism has been proposed based on the results from XPS-analysis, an iodine color test and several other control experiments.

Substrate-controlled selectivity switch in a three-component reaction: sequential synthesis of spiro-oxazolidinedione-cyclopentenones and hydroxy enaminobarbiturates in water.

An efficient eco-friendly catalyst-free three-component domino multicyclization for the synthesis of new spirobicyclic oxazolidinedione containing cyclopentenone moieties has been established by mixing amines, β-dicarbonyl compounds and N,N′-dimethylalloxan in water at room temperature. This domino process involves multiple reactions such as enamination/aldol-like reaction/Stork enamine annulation/intramolecular cyclization under mild conditions.

Photocatalytic Isocyanide-Based Multicomponent Domino Cascade toward the Stereoselective Formation of Iminofurans.

A visible-light-promoted three-component isocyanide-based synthesis of iminofurans is herein reported. The reaction proved to be general in scope and proceeds through a triple domino process. Control experiments with 18O-labeled water and TEMPO provided key mechanistic insights for delineating the reactivity paradigms crucial to design efficient photoredox isocyanide-based domino transformations.