Hoveyda-Grubbs catalyst confined in the nanocages of SBA-1: enhanced recyclability for olefin metathesis

Via a simple adsorption, the second generation Hoveyda-Grubbs catalyst was successfully immobilized on a mesoporous material SBA-1, leading to a highly recyclable solid catalyst for olefin metathesis.     

Olefin metathesis in homogeneous aqueous media catalyzed by conventional ruthenium catalysts

Olefin metathesis in aqueous solvents is sought for applications in green chemistry and with the hydrophilic substrates of chemical biology, such as proteins and polysaccharides. Most demonstrations of metathesis in water, however, utilize exotic complexes. We have examined the performance of conventional catalysts in homogeneous water/organic mixtures, finding that the second-generation Hoveyda-Grubbs catalyst has extraordinary efficiency in aqueous dimethoxyethane and aqueous acetone. High (71-95%) conversions are achieved for ring-closing and cross metathesis of a variety of substrates in these solvent systems.     

A general model for selectivity in olefin cross metathesis

In recent years, olefin cross metathesis (CM) has emerged as a powerful and convenient synthetic technique in organic chemistry; however, as a general synthetic method, CM has been limited by the lack of predictability in product selectivity and stereoselectivity. Investigations into olefin cross metathesis with several classes of olefins, including substituted and functionalized styrenes, secondary allylic alcohols, tertiary allylic alcohols, and olefins with alpha-quaternary centers, have led to a general model useful for the prediction of product selectivity and stereoselectivity in cross metathesis. As a general ranking of olefin reactivity in CM, olefins can be categorized by their relative abilities to undergo homodimerization via cross metathesis and the susceptibility of their homodimers toward secondary metathesis reactions. When an olefin of high reactivity is reacted with an olefin of lower reactivity (sterically bulky, electron-deficient, etc.), selective cross metathesis can be achieved using feedstock stoichiometries as low as 1:1. By employing a metathesis catalyst with the appropriate activity, selective cross metathesis reactions can be achieved with a wide variety of electron-rich, electron-deficient, and sterically bulky olefins. Application of this model has allowed for the prediction and development of selective cross metathesis reactions, culminating in unprecedented three-component intermolecular cross metathesis reactions.     

Reversible aqueous metathesis reactions for potential application in dynamic combinatorial chemistry

Solutions of heterocycles having an allyl sulfide unit and simple alkenes in 50% t-BuOH/H₂O undergo reversible olefin metathesis reactions with the second generation Hoveyda-Grubbs catalyst. The choice of functional groups is limited by competitive chelation of some heterocycles with the catalyst, and other stereoelectronic effects.     

Immobilization of the Grubbs second-generation ruthenium-carbene complex on poly(ethylene glycol): a highly reactive and recyclable catalyst for ring-closing and cross-metathesis

A poly(ethylene glycol)-bound Hoveyda-Grubbs Ru catalyst derived from the Grubbs second-generation Ru carbene complex was synthesized and shown to be highly reactive in the ring-closing metathesis of a wide variety of diene substrates, yielding di-, tri-, and tetra-substituted carbocyclic and heterocyclic olefins. The immobilized catalyst also proved to be highly reactive and recyclable in cross-metathesis and ring-opening/cross-metathesis. In all cases tested, the catalyst exhibited a high level of recyclability and reusability.     

Cross metathesis of alpha-methylene lactones II: gamma- and delta-lactones

[reaction: see text] The cross metathesis reactivities of alpha-methylene-gamma-butyrolactone and an alpha-methylene-delta-lactone have been investigated. alpha-Methylene-gamma-butyrolactone undergoes rapid and efficient olefin isomerization in the presence of second-generation metathesis catalysts. However, cross metathesis can be achieved with the additive 2,6-dichlorobenzoquinone. In contrast, the alpha-methylene-delta-lactone neither isomerizes nor couples under similar conditions.     

A new concept for the noncovalent binding of a ruthenium-based olefin metathesis catalyst to polymeric phases: preparation of a catalyst on Raschig rings

A new concept for noncovalent immobilization of a ruthenium olefin metathesis catalyst is presented. The 2-isopropoxybenzylidene ligand of a Hoveyda-Grubbs carbene is further modified by an additional amino group (7) and immobilization is achieved by treatment with sulfonated polystyrene forming the corresponding ammonium salt. In this novel strategy for the immobilization of ruthenium-based metathesis catalysts, the amino group plays a two-fold role, being first an active anchor for immobilization and second, after protonation, activating the catalysts (electron donating to electron withdrawing activity switch). The polymeric support was prepared by precipitation polymerization which led to small bead sizes (0.2-2 microm) and large surface areas. Compared to commercial resins this tailor-made phase showed superior properties in immobilization of complex 7. This concept of immobilization was applied to glass-polymer composite megaporous Raschig rings. Ru catalyst 7 on Raschig rings was used under batch conditions in various metathesis reactions, including ring-closing (RCM), cross- (CM) and enyne metathesis, to give products of high chemical purity with very low ruthenium contamination levels (21-102 ppm). The same ring can be used for up to 6 cycles of metathesis.     

As low as reasonably achievable catalyst loadings in the cross metathesis of olefins with ethyl acrylate

A series of ruthenium catalysts for olefin metathesis have been screened in the cross metathesis of 1,9-decadiene with ethyl acrylate. Under optimized reaction conditions a catalyst loading of only 100 ppm in respect to double bonds was sufficient for complete conversion of the diene.     

Chloro-substituted Hoveyda-Grubbs ruthenium carbene: Investigation of electronic effects

A series of applications of cross and ring-closing metathesis has been made to investigate the application profile of the chloro-substituted Hoveyda-Grubbs ruthenium carbene in order to evaluate electronic effects resulting from the introduction of a chlorine atom para to the isopropoxy moiety of its parent catalyst.     

Studies related to the total synthesis of the sesquiterpene core of the pyrrolobenzoxazine natural products CJ-12662 and CJ-12663

A highly effective procedure is reported to synthesize a substituted bicyclo[4.2.0]octenol derivative by regioselective cycloaddition of phenyl-1-propynyl sulfide with cyclohexenone followed by selective reduction of the ketone group and reductive elimination of phenylsulfonyl group. The strained cyclobutene ring was then engaged in a ring-opening/cross metathesis sequence in the presence of Hoveyda-Grubbs 2nd generation catalyst. The synthesis serves as a model study toward the synthesis of the sesquiterpene diol portion of the terpenoid pyrrolobenzoxazine alkaloids, CJ-12662 and CJ-12663.     

Cross metathesis assisted solid-phase synthesis of glycopeptoids

A solid-phase synthesis of glycopeptoids was explored through olefin cross metathesis (CM). Peptoids and sugar derivatives with appropriate olefin moieties were coupled in the presence of an olefin metathesis catalyst to afford glycopeptoids in good yields. This systematic solid-phase CM study can provide facile access to the molecular sources of glycopeptidomimetics and postchemical modifications on various molecular scaffolds.     

Cross metathesis with strained exocyclic enones: synthesis of 3-alkylideneoxetan-2-ones from 3-methyleneoxetan-2-ones

[reaction: see text] 3-Alkylideneoxetan-2-ones have been prepared in good to excellent yields with high Z-selectivity by olefin cross metathesis with 3-methyleneoxetan-2-ones in the presence of second generation metathesis catalysts 1 or 2.     

Olefin metathesis catalyst: stabilization effect of backbone substitutions of N-heterocyclic carbene

Ruthenium olefin metathesis catalysts bearing an N-phenyl-substituted N-heterocyclic carbene (NHC) ligand that are resistant to decomposition through C-H activation have been prepared and tested in ring closing metathesis (RCM), cross metathesis (CM), and ROMP reactions. The N, N'-diphenyl-substituted NHC complex proved to be one of the most efficient catalysts in RCM to form tetrasubstituted olefins.     

Synthesis of tetrasubstituted alkenes via metathesis

Fully substituted olefin generation via metathesis is presented. Catalyst development, optimization of reaction conditions and substrate screening are included. In addition, asymmetric alkene metathesis, the cross metathesis reaction for this transformation and its application in natural products will be discussed.     

A diversity-oriented synthetic approach to bengamides

A new approach to the bengamides, a new class of antitumor natural products of marine origin, is reported from epoxyamides, prepared by reaction of aldehydes with sulfur ylides. The synthetic strategy has been designed for the delivery of a wide array of analogues. Thus, the terminal alkyl substituent is introduced by a cross olefin metathesis from the corresponding terminal olefin. The combination of cross olefin metathesis, introduction of different nucleophiles by the oxirane ring opening and the introduction of different amines via amide bond formation, can produce a wide array of bengamides analogues.     

Cross metathesis approach to retinoids and other β-apocarotenoids

Cross metathesis (CM) reactions between polyenes, such as β-carotene, canthaxanthin or retinyl acetate, and various alkenes or dienes in the presence of second generation Hoveyda-Grubbs (H II) or Grubbs (G II) catalysts were investigated. Depending on the cross partner different apocarotenoids were obtained. Cross metathesis reactions of retinyl acetate proved to be fully regioselective. Carotenoid CM reactions afforded mixtures of two products due to competing cleavage of the C11-C12 and C15-C15′ double bonds. However, regioselectivity can be controlled by choice of appropriate reaction conditions. The reactions of polyenes with dienes worked better in respect of yields and diastereoselectivities than those with monounsaturated cross partners.     

Total synthesis of Bengamide E and analogues by modification at C-2 and at terminal olefinic positions

[Reaction: see text]. The total synthesis of the natural product Bengamide E, one of the members of a new class of antitumor natural products of marine origin, is reported based on a convergent and flexible synthetic route featuring an oxirane ring-opening reaction and an olefin cross metathesis. In a similar way, analogues structurally modified at C-2 and at the terminal vinyl positions were prepared by introduction of various nucleophiles and alkyl substituents during the epoxide opening and the olefin cross metathesis steps, respectively. These studies demonstrate the validity of our synthetic strategy, although they reveal some problems associated with the olefin cross metathesis, whose efficiency depends on the substituent at the C-2 position as well as the steric environment of the alkene.     

Sphingolipid synthesis via olefin cross metathesis: preparation of a differentially protected building block and application to the synthesis of D-erythro-ceramide

The sphingolipid backbone is readily assembled by E-selective olefin cross metathesis of a suitable building block.     

Electrochemically reduced tungsten‐based active species as catalysts for cross‐metathesis reactions: cross‐metathesis of non‐functionalized olefins

The electrochemical reduction of WCl₆ results in the formation of an active olefin (alkene) metathesis catalyst. The application of the WCl₆–e^?–Al–CH₂Cl₂ catalyst system to cross‐metathesis reactions of non‐functionalized acyclic olefins is reported. Undesirable reactions, such as double‐bond shift isomerization and subsequent metathesis, were not observed in these reactions. Cross‐metathesis of 7‐tetradecene with an equimolar amount of 4‐octene generated the desired cross‐product, 4‐undecene, in good yield. The reaction of 7‐tetradecene with 2‐octene, catalyzed by electrochemically reduced tungsten hexachloride, resulted in both self‐ and cross‐metathesis products. The cross‐metathesis products, 2‐nonene and 6‐tridecene, were formed in larger amounts than the self‐metathesis products of 2‐octene. The optimum catalyst/olefin ratio and reaction time were found to be 1 : 60 and 24 h, respectively. The cross‐metathesis of symmetrical olefins with α‐olefins was also studied under the predetermined conditions. Copyright © 2003 John Wiley & Sons, Ltd.