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Bimetallic nanostructures comprising plasmonic and catalytic components have recently emerged as a promising approach to generate a new type of photo-enhanced nanoreactors. Most designs however concentrate on plasmon-induced charge separation, leaving photo-generated heat as a side product.
This work presents a photoreactor based on Au-Pd nanorods with an optimized photothermal conversion, which aims to effectively utilize the photo-generated heat to increase the rate of Pd-catalyzed reactions. Dumbbell-shaped Au nanorods were fabricated via a seed-mediated growth method using binary surfactants. Pd clusters were selectively grown at the tips of the Au nanorods, using the zeta potential as a new synthetic parameter to indicate the surfactant remaining on the nanorod surface.
The photothermal conversion of the Au-Pd nanorods was improved with a thin layer of polydopamine (PDA) or TiO2.
As a result, a 60% higher temperature increment of the dispersion compared to that for bare Au rods at the same light intensity and particle density could be achieved.
The catalytic performance of the coated particles was then tested using the reduction of 4-nitrophenol as the model reaction. Under light, the PDA-coated Au-Pd nanorods exhibited an improved catalytic activity, increasing the reaction rate by a factor 3.
An analysis of the activation energy confirmed the photoheating effect to be the dominant mechanism accelerating the reaction. Thus, the increased photothermal heating is responsible for the reaction acceleration.
Interestingly, the same analysis shows a roughly 10% higher reaction rate for particles under illumination compared to under dark heating, possibly implying a crucial role of localized heat gradients at the particle surface.
Finally, the coating thickness was identified as an essential parameter determining the photothermal conversion efficiency and the reaction acceleration.
The molecular structures of three closely related isoflavones have been determined by single crystal X-ray diffraction and have been analysed by geometry matching with the CSD, Hirshfeld surface analysis and analysis of stacking interactions with the Aromatic Analyser program (CSD). The formation of the supramolecular structure by non-covalent interactions was studied and substantial differences in the macroscopic properties e.g., the solubility, were correlated with hydrogen bonding and pi-stacking interactions. Moreover, a correlation between the supramolecular structure, the torsion angle (between benzopyran group and aryl group), and macroscopic properties was determined in the three compounds.
Ortho-allyloxy alkinyl benzenes undergo, upon microwave irradiation in dimethylformamide, a tandem sequence of Claisen-rearrangement and 5-endo-dig cyclization to furnish 7-allyl-substituted benzofurans. With terminal alkynes, chroman-4-ones and enaminoketones become the main products. A mechanistic proposal for this observation relies on a reaction of the starting material with the solvent dimethylformamide under the microwave conditions.
The one-pot synthesis of 8-prenylcoumarins from 1,1-dimethylallylated salicylaldehydes and the stabilized ylide [(ethoxycarbonyl)methylene]triphenylphosphorane under microwave conditions was found to have a limited scope. The sequence suffers from a difficult and sometimes low-yielding synthesis of the precursors and from a competing deprenylation upon microwave irradiation. This side reaction occurs in particular with electron rich arenes with two or more alkoxy groups at adjacent positions, a prominent substitution pattern in naturally occurring 8-prenylcoumarins. Both limitations of this one-step sequence were overcome by a two-step synthesis consisting of a microwave-promoted tandem allyl ether Claisen rearrangement/Wittig olefination and a subsequent olefin cross metathesis with 2-methyl-2-butene. The cross metathesis step proceeds with a high selectivity and yields exclusively the desired prenyl, rather than the alternative crotyl substituent. Several naturally occurring 8-prenylcoumarins that were previously inaccessible have been synthesized in good overall yields along this route.
8-Allylcoumarins are conveniently accessible through a microwave-promoted tandem Claisen rearrangement/Wittig olefination/cyclization sequence. They serve as a versatile platform for the annellation of five- to seven-membered rings using ring-closing olefin metathesis (RCM). Furano-, pyrano-, oxepino- and azepinocoumarins were synthesized from the same set of precursors using Ru-catalyzed double bond isomerizations and RCM in a defined order. One class of products, pyrano[2,3-f]chromene-2,8-diones, were inaccessible through direct RCM of an acrylate, but became available from the analogous allyl ether via an assisted tandem catalytic RCM/allylic oxidation sequence.
Prenylated flavanones were obtained from ortho-allyloxy chalcones through a one-pot sequence of Claisen rearrangement and 6-endo-trig cyclization, followed by olefin cross metathesis of the intermediate allyl flavanones with 2-methyl-2-butene. The synthetic utility of this route is illustrated for the synthesis of several naturally occurring prenyl flavanones.
alpha-Methylene-gamma-butyrolactone and alpha-methylene-gamma-valerolactone undergo Pd-catalyzed Matsuda-Heck couplings with arene diazonium salts to alpha-benzyl butenolides or pentenolides, respectively, or to alpha-benzylidene lactones. The observed regioselectivity is strongly ring size dependent, with six-membered rings giving exclusively alpha-benzyl pentenolides, whereas the five-membered alpha-methylene lactone reacts to mixtures of regioisomers with a high proportion of (E)-alpha-benzylidene-gamma-butyrolactones. DFT calculations suggest that the reasons for these differences are not thermodynamic but kinetic in nature. The relative energies of the conformers of the Pd sigma-complexes resulting from insertion into the Pd-aryl bond were correlated with the dihedral angles between Pd and endo-beta-H. This correlation revealed that in the case of the six-membered lactone an energetically favorable conformer adopts a nearly synperiplanar Pd/endo-beta-H arrangement, whereas for the analogous Pd sigma-complex of the five-membered lactone the smallest Pd/endo-beta-H dihedral angle is observed for a conformer with a comparatively high potential energy. The optimized conditions for Matsuda-Heck arylations of exo-methylene lactones were eventually applied to the synthesis of the natural product anemarcoumarin A.
Arene diazonium salts undergo Matsuda-Heck reactions with vinylsulfonates and -sulfonamides to give styrylsulfonic acid derivatives in high to excellent yields and with high to excellent selectivities. By quantifying the evolution of nitrogen over time in a gas-meter apparatus, the reactivities of ethylvinylsulfonate and the benchmark olefin methyl acrylate were compared for an electron-rich and an -deficient arene diazonium salt. Tertiary sulfonamides react in Matsuda-Heck couplings with high conversions, but require long reaction times, which prevents the determination of kinetic data through the measurement of nitrogen evolution. Secondary sulfonamides were found to be unreactive. From these results, the following order of reactivity could be deduced: H2C=CHCO2Me > H2C=CHSO2OEt > H2C=CHSO2N(Me)Bn >> H2C=CHSO2NHBn. Through the Matsuda-Heck coupling of 5-indolyldiazonium salt and a tertiary vinylsulfonamide, the synthesis of the C-5-substituted indole part of the antimigraine drug naratriptan was accomplished in high yield.
The Pd-catalyzed Heck-type coupling (Matsuda Heck reaction) of electron rich arene diazonium salts with electron deficient olefins has been exploited for the synthesis of phenylpropanoid natural products. Examples described herein are the naturally occurring benzofurans methyl wutaifuranate, wutaifuranol, wutaifuranal, their 7-methoxy derivatives, and the O-prenylated natural products boropinols A and C.
3,4-Dihydro-2-H-pyran and oxalyl chloride react, depending on the conditions, to keto esters, a pyran-3- carboxylic acid or derivatives thereof, or to an hitherto unknown bicyclic acetal containing a vinyl chloride moiety. The structure of the latter product has been unambiguously elucidated by single-crystal X-ray structure analysis. A mechanism for its formation is proposed.
A protected derivative of (3R, 4R)-hexa-1,5-diene-3,4-diol, a conveniently accessible C-2-symmetric building block, undergoes single or double cross metathesis with methyl acryl-ate. The cross metathesis products are amenable to stereoselective conjugate addition reactions and can be converted into either gamma-butyrolactones or gamma-lactams.
The enantiomerically pure C-2-syrnmetrical hexa-1,5-diene-3,4-diol is selectively monopropargylated. The products undergo ring-closing enyne metathesis to give exclusively dihydropyrans as single stereoisomers. An unprotected hydroxy group is identified as the factor controlling the ring-size selectivity.
A sequence of selective monoprotection and Rh-catalyzed enantioconservative allylic subEtitution is established as a desymmetrization strategy for C-2-symmetric hexa-1,5-diene-3,4-diol. A benzyl protecting group and ethyl carbonate as a leaving group emerged as the most useful combination with respect to reproducibility, stereoselectivity, and yield: A remarkable deviation from the normally observed regiospecificity of Rh-catalyzed allylic alkylations was observed for unprotected carbonates. In this case, a linear, rather than a branched alkylation product was obtained exclusively.
The reaction between propargyl ethers of hydroxybenzaldehydes and the ylide ethyl (triphenylphosphoranylidene)acetate was carried out under microwave irradiation to regioselectively afford angular pyranocoumarins. The chromene and coumarin heterocyclic scaffolds were simultaneously formed in the same synthetic step without changing the reaction conditions. The natural products seselin, braylin, and dipetalolactone were among the products synthesized by this method.
Tandem Claisen Rearrangement/6-endo Cyclization Approach to Allylated and Prenylated Chromones
(2015)
Allyl, dimethylallyl and prenyl ethers derived from o-acyl-phenols reacted upon microwave irradiation to form C-allylated or -prenylated chromone derivatives, depending on the substitution pattern of the arene and the allyl substituent. The reaction proceeds through a tandem Claisen rearrangement and 6-endo-trig or 6-endo-dig cyclization sequence. For prenyl ethers, the tandem sequence can be extended by a Cope rearrangement to furnish 6-prenylchromones. The method is potentially useful for the synthesis of natural products and drugs.
User-friendly protocols for the protecting group-free synthesis of 2,2'-biphenols via Suzuki-Miyaura coupling of o-halophenols and o-boronophenol are presented. The reactions proceed in water in the presence of simple additives such as K2CO3, KOH, KF, or TBAF and with commercially available Pd/C as precatalyst. Expensive or laboriously synthesized ligands or other additives are not required. In the case of bromophenols, efficient rate acceleration and short reaction times were accomplished by microwave irradiation.
ortho-Aryl phenols, synthesized via protecting group free Suzuki-Miyaura coupling of ortho-halophenols and arene boronic acids, undergo a cyclization to dibenzofurans via oxidative C-H activation. The reaction proceeds under microwave irradiation in short reaction times using catalytic amounts of Pd(OAc)(2) without additional ligands.
Magnaldehydes B and E along with their 4'-methylated derivatives are naturally occurring 2,4'-biphenols that have been isolated from the Magnoliaceae. Herein, these natural products have been synthesized from a common intermediate, which was obtained by a microwave-promoted, hetero-geneously catalyzed, and protecting-group-free Suzuki-Miyaura coupling reaction in an aqueous medium. These reaction conditions were also successfully applied to a one-step synthesis of the slime mold metabolite dictyobiphenyl B.
The Suzuki-Miyaura couplings of o-, m-, and p-halophenols with o-, m-, and p-phenol boronic acids were investigated for all combinations under standardized conditions, using Pd/C as a heterogeneous catalyst and water as a solvent. In the case of iodophenols, conventional heating was used, while for bromophenols significantly better results could be obtained using microwave irradiation. This systematic study revealed that 2,4'-biphenol is particularly difficult to access, irrespective of the starting materials used, but that these difficulties can be overcome by using different additives. The conclusions drawn from this investigation allowed us to identify conditions for the protecting group-free or minimized total synthesis of biaryl-type phytoalexins. These compounds possess antibacterial activity and are produced by fruit trees as a response to microbial infection.
para-Substituted aryl prenyl ethers undergo a deprenylation reaction upon microwave irradiation. This offers the opportunity to use a prenyl ether as a thermolabile protecting group in the synthesis of natural products with a chromone structure, which proceeds via a tandem deprenylation/6-endo-cyclization sequence.
Allyl, dimethylallyl, crotyl, and prenyl ethers of various aromatic ortho-hydroxy carbonyl compounds undergo a tandem sequence of Claisen rearrangement, carbonyl olefination, and cyclization upon microwave irradiation in the presence of a stabilized ylide. The products are multiply substituted 6- or 8-allylated or prenylated coumarins (2H-chromen-2-ones).
(5R,6S)-6-Acetoxy-5-hexadecanolide (MOP) is the oviposition pheromone of the mosquito Cx. quinquefasciatus, a vector of pathogens causing a variety of tropical diseases. We describe and evaluate herein three syntheses of MOP starting from mannitol-derived (3R,4R)-hexa-1,5-diene-3,4-diol. This C-2-symmetric building block is elaborated through bidirectional olefin metathesis reactions into 6-epi-MOP, which was converted into MOP via Mitsunobu inversion. The shortest of the three routes makes use of two sequential cross-metathesis reactions and an assisted tandem catalytic olefin reduction, induced by an in situ conversion of a Ru-carbene to a Ru-hydride.
Enantioselective total syntheses of both enantiomers of the recently isolated decanolide natural product seimatopolide A are described. The C-2-symmetric building blocks (R,R)-hexa-1,5-diene-3,4-diol (derived from D-mannitol) and its enantiomer (derived from L-(+)-tartrate) serve as key starting materials, which are elaborated in a bidirectional way using a selective mono-cross-metathesis, regio- and stereoselective epoxidation, and regioselective reductive epoxide opening to furnish the first fragment. Both enantiomers of the second fragment, 3-hydroxypent-4-enoic acid, were conveniently obtained through a lipase-catalyzed kinetic resolution and merged with the first fragment via Shiina esterification. An E-selective ring-closing metathesis was used to access the 10-membered lactone. A comparison of the specific optical rotations of synthetic seimatopolides with those reported for the natural product suggests that the originally assigned (3R,6R,7R,9S)-configuration should be corrected to (3S,6S,7S,9R).
Stereoselective synthesis of dienyl phosphonates via extended tethered ring-closing metathesis
(2013)
Allylphosphonates of allylic alcohols were converted to conjugated dienyl phosphonates in a one-flask reaction, comprising a ring-closing metathesis (RCM), a base-induced ring-opening, and an alkylation. The ring-opening proceeds with very high diastereoselectivity, giving exclusively the (1Z,3E)-configured dienes. Single diastereomers and mixtures of diastereomers can be used as starting materials without noticeable effect on the diastereoselectivity of the sequence.
Starting from the conveniently available ex-chiral pool building block (R,R)-hexa-1,5-diene-3,4-diol, the ten-membered ring lactones stagonolide E and curvulide A were synthesized using a bidirectional olefin-metathesis functionalization of the terminal double bonds. Key steps are (i) a site-selective cross metathesis, (ii) a highly diastereoselective extended tethered RCM to furnish a (Z,E)-configured dienyl carboxylic acid and (iii) a Ru-lipase-catalyzed dynamic kinetic resolution to establish the desired configuration at C9. Ring closure was accomplished by macrolactonization. Curvulide A was synthesized from stagonolide E through Sharpless epoxidation.
alpha,beta-Unsaturated d-lactones are accessible via a sequential ring-closing metathesis (RCM) double-bond migration reaction starting from butenoates of allyl alcohols. This approach proceeds efficiently with lower catalyst loadings and higher initial substrate concentrations compared to the alternative RCM of acrylates derived from homoallylic alcohols.
A one-flask reaction sequence comprising ring closing metathesis (RCM) of butenoates derived from allylic alcohols and a base-mediated ring opening gives 2Z,4E-configured dienoic acids in high yields and stereoselectivities. Application of the method to the synthesis of the natural product fusanolide A suggests that the originally published structure was erroneously assigned and should be revised.
A sequential ruthenium-catalyzed ring-closing metathesis-transfer hydrogenation sequence has been established as a synthesis of chromanes starting from 2-(allyloxy)styrenes. The sequence requires only one precatalyst, the first-generation Grubbs catalyst, which is converted into a ruthenium hydride species in situ. Propan-2-ol serves as a chemical trigger for the formation of the ruthenium hydride and as hydrogen source.
The synthesis of 7-methoxy-8-(4-methyl-3-furyl)-2H-chromen-2-one, a natural product with antileishmanial activity recently isolated from the plant Galipea panamensis, is described. The key step is a Suzuki-Miyaura coupling of a furan-3-boronic acid and an 8-halocoumarin, which is advantageously synthesized using a ring-closing metathesis reaction. Several non-natural analogues are also available along these lines.
An assisted tandem catalytic transformation of diallyl amines and diallyl ethers into N-aryl pyrroles and furans, respectively, is described. The sequence relies on ring closing metathesis followed by dehydrogenation of the initially formed dihydropyrroles and dihydrofurans. Both steps are Ru-catalyzed, but the sequence requires only one precatalyst, because conversion of the metathesis catalyst into the dehydrogenation catalyst is achieved in situ, triggered by the oxidant tert-butyl hydroperoxide.
1,2-Diketones were synthesized from styrenes by combining a cross metathesis and a Ru-catalyzed alkene oxidation to an assisted tandem catalytic sequence. The synthesis relies on the use of just one metathesis precatalyst, which was in situ converted to the oxidation catalyst by addition of an alkyl hydroperoxide as a chemical trigger and oxidant. The one-flask sequence can be extended beyond 1,2-diketones to quinoxalines, by condensation of the oxidation products with ortho-phenylenediamine.
The first total synthesis of the natural product (3S,7R)-5,6-dehydro-de-O-methyl centrolobine and various analogues is reported, using a highly regio- and diastereoselective Mizoroki-Heck reaction of phenol diazonium salts and enantiopure dihydropyrans. The assigned relative configuration was confirmed by single-crystal X-ray structure analysis, but a revision of the absolute configuration is proposed based on polarimetric measurement.
All stereoisomers of the natural product centrolobine are selectively synthesized, by starting from a common precursor. Key steps are an enantioselective allylation with enantiomerically pure allylsilanes, a tandem ring-closing metathesis-isomerization reaction, and a Heck reaction by using an arene diazonium salt. By choosing appropriate conditions for the final deprotection step, either the cis-configured centrolobines or their epimers are selectively obtained.
In most cases where ring closing metathesis is applied to the synthesis of heterocycles, alpha,omega-dienes are used as precursors. If substrates containing more than two double bonds are subjected to a metathesis reaction, carba- or heterocycles bearing additional exocyclic alkene functionality result, or multiple ring closing processes occur. This offers interesting and potentially very useful synthetic perspectives. On the other hand, selectivity problems need to be addressed as the cyclization of substrates with more than two double bonds available for olefin metathesis may result in constitutional isomers or stereoisomers. This review highlights problems and opportunities evolving from ring closing metathesis of tri-, tetra-, and polyenes as a strategy for the selective synthesis of functionalized heterocycles. The chapter on RCM of trienes is subdivided according to the symmetry of the metathesis precursor. The following two chapters deal with the double or multiple RCM of tetra- or polyenes. These processes are further classified according to the preferred cyclization mode. Finally, the application of cascade or domino metathesis reactions to the synthesis of heterocycles will be discussed. These processes can be classified into those where exclusively C-C-double bonds take part in the metathesis reaction, and those where one or more C-C-triple bonds are involved
N-Allyl-N-homoallylamines were converted in one step into cyclic enamides via a ruthenium-catalyzed assisted tandem catalytic ring-closing metathesis-isomerization sequence. The sequence relies on the in situ transformation of a metathesis active Ru-carbene into an isomerization active Ru-hydride by addition of hydroxide as a chemical trigger.
Cross metathesis of allyl alcohols: how to suppress and how to promote double bond isomerization
(2014)
Under standard conditions the cross metathesis of allyl alcohols and methyl acrylate is accompanied by the formation of ketones, resulting from uncontrolled and undesired double bond isomerization. By conducting the CM in the presence of phenol, the catalyst loading and the reaction time required for quantiative conversion can be reduced, and isomerization can be suppressed. On the other hand, consecutive isomerization can be deliberately promoted by evaporating excess methyl acrylate after completing cross metathesis and by adding a base or silane as chemical triggers.
The rare carbohydrate L-(+)-noviose was synthesized from enantiomerically pure L-lactate. The configuration at C-4 was established by diastereoselective nucleophilic addition to an in-situ-generated lactaldehyde. The resulting homoallylic alcohol was further transformed into a set of ring-closing metathesis (RCM) precursors. These compounds were converted into noviose in few steps using RCM and RCM-allylic-oxidation sequences.
Cross metathesis of allyl alcohols how to suppress and how to promote double bond isomerization
(2013)
Under standard conditions the cross metathesis of allyl alcohols and methyl acrylate is accompanied by the formation of ketones, resulting from uncontrolled and undesired double bond isomerization. By conducting the CM in the presence of phenol, the catalyst loading and the reaction time required for quantiative conversion can be reduced, and isomerization can be suppressed. On the other hand, consecutive isomerization can be deliberately promoted by evaporating excess methyl acrylate after completing cross metathesis and by adding a base or silane as chemical triggers.
Butenolides, obtained by ring-closing metathesis (RCM) of acrylates, undergo quantitative deprotonation with amide bases. Trapping of the resulting anions with electrophiles, for example, chlorophosphates, give furans. Subsequent DielsAlder reaction and acid-catalysed rearrangement of the resulting oxabicyclonorbornadienes give substituted benzenes.
2,5-Disubstituted furans were synthesized by one-flask Heck arylation/oxidation sequences. The starting materials are 2-substituted 2,3-dihydrofurans, conveniently available by RCM/isomerization sequences, and arenediazonium salts. These react in ligand-free Heck reactions to afford 2,5-disub-stituted 2,5-dihydrofurans, which are oxidized to the corresponding furans without isolation or intermediate workup. The oxidation is conveniently achieved with chloranil or DDQ, depending on the substrate.
The acetamide group enables regioselective oxidative ortho-C-H activation reactions, such as Pd-catalyzed acylation. The synthetic utility of these transformations can be significantly enhanced by using the acetamide as a quasi-leaving group in a subsequent conventional Pd-catalyzed coupling or cross-coupling reaction. The concept is illustrated herein for the synthesis of o-alkenyl- and o-arylphenones, which have potential for the synthesis of arylated aromatic heterocycles.
Unlike their ortho counterparts, meta- and para-acetamidoanilines can be converted into the corresponding acetamidoarenediazonium salts. These offer various opportunities for multiple Pd-catalyzed arene functionalization reactions, such as Matsuda-Heck-, Suzuki-Miyaura- or Fujiwara-Moritani couplings.