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.     

Ring-closing metathesis of α-ester-substituted enol ethers: application to the shortest synthesis of KDO

Ring-closing metathesis reactions of α-ester-substituted enol ethers are described. In the case of unsubstituted terminal olefins, isomerization prior to cyclization was observed as an undesired side reaction, which could not be completely inhibited. Furthermore, this methodology was applied to a formal synthesis of KDO, which now represents the shortest synthetic pathway to KDO and its deoxy analogue. Interestingly, in this route olefin isomerization was not observed, presumably due to the increased steric environment of the double bond. Finally, an efficient two-step conversion to transform an alcohol into an α-alkoxy acrylate is also described.     

The preparation of C-glycosyl amino acids—an examination of olefin cross-metathesis

A study investigating the structural features directing olefin cross-metathesis to afford C-glycoamino acids was carried out. These results lead to an appreciation of the importance of proximal functionality to the relative reactivity of olefins in metathesis reactions providing a variable that is useful to suppress undesirable self-metathesis.     

Isomerizing olefin metathesis as a strategy to access defined distributions of unsaturated compounds from Fatty acids

The dimeric palladium(I) complex [Pd(μ-Br)(t)Bu(3)P](2) was found to possess unique activity for the catalytic double-bond migration within unsaturated compounds. This isomerization catalyst is fully compatible with state-of-the-art olefin metathesis catalysts. In the presence of bifunctional catalyst systems consisting of [Pd(μ-Br)(t)Bu(3)P](2) and NHC-indylidene ruthenium complexes, unsaturated compounds are continuously converted into equilibrium mixtures of double-bond isomers, which concurrently undergo catalytic olefin metathesis. Using such highly active catalyst systems, the isomerizing olefin metathesis becomes an efficient way to access defined distributions of unsaturated compounds from olefinic substrates. Computational models were designed to predict the outcome of such reactions. The synthetic utility of isomerizing metatheses is demonstrated by various new applications. Thus, the isomerizing self-metathesis of oleic and other fatty acids and esters provides olefins along with unsaturated mono- and dicarboxylates in distributions with adjustable widths. The cross-metathesis of two olefins with different chain lengths leads to regular distributions with a mean chain length that depends on the chain length of both starting materials and their ratio. The cross-metathesis of oleic acid with ethylene serves to access olefin blends with mean chain lengths below 18 carbons, while its analogous reaction with hex-3-enedioic acid gives unsaturated dicarboxylic acids with adjustable mean chain lengths as major products. Overall, the concept of isomerizing metatheses promises to open up new synthetic opportunities for the incorporation of oleochemicals as renewable feedstocks into the chemical value chain.     

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.     

Prevention of undesirable isomerization during olefin metathesis

1,4-Benzoquinones have been found to prevent olefin isomerization of a number of allylic ethers and long-chain aliphatic alkenes during ruthenium-catalyzed olefin metathesis reactions. Electron-deficient benzoquinones are the most effective additives for the prevention of olefin migration. This mild, inexpensive, and effective method to block olefin isomerization increases the synthetic utility of olefin metathesis via improvement of overall product yield and purity.     

Decomposition of a key intermediate in ruthenium-catalyzed olefin metathesis reactions

Dinuclear ruthenium complex, with a bridging carbide and a hydride ligand, and methyltricyclohexylphosphonium chloride result from thermal decomposition of olefin metathesis catalyst, (IMesH2)(PCy3)(Cl)2Ru=CH2. Involvement of dissociated phosphine in the decomposition is proposed. The dinuclear complex has catalytic olefin isomerization activity, which can be responsible for competing isomerization processes in certain olefin metathesis reactions.     

Metathesis reactions with a low-cost spinning disk system

ABSTRACT

Experimental procedures have been developed to provide at the laboratory scale an efficient and relatively inexpensive continuous flow processing system to undertake metathesis chemistry. Glass discs, coated with porous silica particles impregnated with Grubbs (I) generation or Hoveyda–Grubbs (II) generation catalysts through non-covalent interactions, have been successfully used as annular zones for in situ metathesis reactions. The supported catalysts were active for ring closing metathesis and self-metathesis reactions with a variety of substrates with nearly quantitative conversion depending on the substrate structure. Advantages of these procedures include the ability to conduct reactions efficiently at small (low mmole) scale under ambient laboratory conditions, thereby avoiding the need for high energy/thermal procedures. Multiple experiments can be undertaken during the same day if catalyst screening is required. Moreover, separation of starting materials from products can be achieved using the same unit operations, avoiding the need for additional purification steps, thereby reducing the total solvent consumption.     

Tandem Catalysis Utilizing Olefin Metathesis Reactions

Since olefin metathesis transformation has become a favored synthetic tool in organic synthesis, more and more distinct non‐metathetical reactions of alkylidene ruthenium complexes have been developed. Depending on the conditions applied, the same olefin metathesis catalysts can efficiently promote isomerization reactions, hydrogenation of C=C double bonds, oxidation reactions, and many others. Importantly, these transformations can be carried out in tandem with olefin metathesis reactions. Through addition of one portion of a catalyst, a tandem process provides structurally advanced products from relatively simple substrates without the need for isolation of the intermediates. These aspects not only make tandem catalysis very attractive from a practical point of view, but also open new avenues in (retro)synthetic planning. However, in the literature, the term “tandem process” is sometimes used improperly to describe other types of multi‐reaction sequences. In this Concept, a number of examples of tandem catalysis involving olefin metathesis are discussed with an emphasis on their synthetic value.     

New selectivities from old catalysts. Occlusion of Grubbs’ catalysts in PDMS to change their reactions

This article describes new selectivities for Grubbs’ first and second generation catalysts when occluded in a hydrophobic matrix of polydimethylsiloxane (PDMS). Occlusion of catalysts in mm-sized slabs of PDMS is accomplished by swelling with methylene chloride then removing the solvent under vacuum. The catalysts are homogenously dissolved in PDMS yet remain catalytically active. Many substrates that react by olefin metathesis with Grubbs’ catalysts freely dissolved in methylene chloride also react by olefin isomerization with occluded catalysts. Eleven examples of substrates that exhibit dual reactivity by undergoing olefin isomerization with occluded catalysts and olefin metathesis with catalysts dissolved in methylene chloride are reported. Most of these substrates have olefins with allylic phosphine oxides, carbonyls, or ethers. Control experiments demonstrate that isomerization is occurring in the solvent by decomposition of the catalyst from a ruthenium carbene to a proposed ruthenium hydride. This work was extended by heating occluded Grubbs’ first generation catalyst to 100 °C in 90% MeOH in H₂O in the presence of various alkenes to transform the Grubbs’ catalyst into an isomerization catalyst for unfunctionalized olefins. This work demonstrates that occlusion of organometallic catalysts in PDMS has important implications for their reactions and can be used as a method to control which reactions they catalyze.     

Ethenolysis: A Green Catalytic Tool to Cleave Carbon–Carbon Double Bonds

Remarkable innovations have been made in the field of olefin metathesis due to the design and preparation of new catalysts. Ethenolysis, which is cross‐metathesis with ethylene, represents one catalytic transformation that has been used with the purpose of cleaving internal carbon–carbon double bonds. The objectives were either the ring opening of cyclic olefins to produce dienes or the shortening of unsaturated hydrocarbon chains to degrade polymers or generate valuable shorter terminal olefins in a controlled manner. This Review summarizes several aspects of this reaction: the catalysts, their degradation in the presence of ethylene, some parameters driving their productivity, the side reactions, and the applications of ethenolysis in organic synthesis and in potential industrial applications.     

Non-metathesis reactions of ruthenium carbene catalysts and their application to the synthesis of nitrogen-containing heterocycles

Non-metathesis reactions of ruthenium carbene catalysts, such as olefin isomerization, hydrogenation, radical reaction, activation of silane, cyclopropanation, epimerization cocyclopropane, [3 + 2] cycloaddition, and cycloisomerization, are summarized. The utility of these reactions was demonstrated by the synthesis of indole using olefin isomerization and subsequent ring-closing metathesis, the synthesis of indoline using cycloisomerization, and the synthesis of the putative structure of fistulosin using cycloisomerization as a key step.     

Organometall‐Reaktionen in Wasser

Water has attracted significant attention as an alternative solvent for organometallic reactions because it is nontoxic, nonflammable, and inexpensive, and is easily separated from organic products. Organometallic reactions, like the palladium‐catalyzed couplings of organic halides with organoboron compounds (Suzuki) and organotin reagents (Stille), are among the most widely used reactions for the formation of carbon‐carbon bonds. Owing to the discovery of water‐soluble, sulfonated phosphane derivatives and particularly the design of water‐soluble palladium‐catalysts it was possible to import these reactions into aqueous media. Another efficient, metal‐catalyzed, carbon‐carbon bond‐forming process that is nowadays possible in aqueous media is the olefin metathesis. The approaches so far include the use of water‐soluble ruthenium‐catalysts, surfactants and additives, ultrasonication, the introduction of polar quaternary ammonium groups or the incorporation of PEG as a water solubilizing moiety. The last point bears also a great potential for further developments in the removal of ruthenium‐containing byproducts. Additionally, water is the ideal reaction environment for polar, water soluble substrates such as natural product or pharmaceuticals.     

Benchmarked Intrinsic Olefin Metathesis Activity: Mo vs. W

Combining Surface Organometallic Chemistry with rigorous olefin purification protocol allows evaluating and comparing the intrinsic activities of Mo and W olefin metathesis catalysts towards different types of olefin substrates. While well‐defined silica‐supported Mo and W imido‐alkylidenes show very similar activities in metathesis of internal olefins, Mo catalysts systematically outperform their W analogs in metathesis of terminal olefins, consistent with the formation of stable unsubstituted W metallacyclobutanes in the presence of ethylene. However, Mo catalysts are more prone to induce olefin isomerization, in particular when ethylene is present, probably because of their propensity to undergo more easily reduction processes.     

Formal synthesis of schulzeines B and C

A formal synthesis of schulzeines B and C, marine natural products with inhibitory effect against α-glucosidase, has been achieved. The key reactions of the synthesis are N-acyliminium ion cyclization, Sharpless asymmetric dihydroxylation, olefin cross metathesis, and asymmetric allylboration.     

The doping effect of fluorinated aromatic solvents on the rate of ruthenium-catalysed olefin metathesis

A study concerning the effect of using a fluorinated aromatic solvent as the medium for olefin metathesis reactions catalysed by ruthenium complexes bearing N-heterocyclic carbene ligands is presented. The use of fluorinated aromatic hydrocarbons (FAH) as solvents for olefin metathesis reactions catalysed by standard commercially available ruthenium pre-catalysts allows substantially higher yields of the desired products to be obtained, especially in the case of demanding polyfunctional molecules, including natural and biologically active compounds. Interactions between the FAH and the second-generation ruthenium catalysts, which apparently improve the efficiency of the olefin metathesis transformation, have been studied by X-ray structure analysis and computations, as well as by carrying out a number of metathesis experiments. The optimisation of reaction conditions by using an FAH can be regarded as a complementary approach for the design of new improved ruthenium catalysts. Fluorinated aromatic solvents are an attractive alternative medium for promoting challenging olefin metathesis reactions.     

The facile preparation of alkenyl metathesis synthons

We report synthetic methodology allowing the preparation of any length alkenyl halide from inexpensive starting reagents. Standard organic transformations were used to prepare straight chain α-olefin halides in excellent overall yields with no detectable olefin isomerization and full recovery of any unreacted starting material. Reported transformations can be used for the selective incorporation of pure α-olefin metathesis sites in highly functionalized molecules.     

过渡金属催化的6-苯基-5,6-二氢-2H-吡喃-2-酮的合成——推荐一个大学有机化学综合实验

有机合成中,碳-碳键的形成和断裂是一个永恒的热门话题,科学家为此发展了很多形成碳-碳键的方法。在这一领域,诞生了不少诺贝尔化学奖的成果,格氏反应和烯烃复分解反应就是其中的经典案例。烯烃复分解反应提供了一种连接sp2-碳和sp2-碳的全新思路,发展出了一些活性分子全合成的高效路径。因而,2005年的诺贝尔化学奖授予了对烯烃复分解反应有杰出贡献的三位科学家。本有机化学综合实验由三个反应构成,包括改进的格氏反应、DMAP催化的酯化反应和关环烯烃复分解反应。每一个反应都可独立成为一个基础有机化学实验,三步的连续反应可以作为一个综合多步合成实验。本实验有助于理解有机合成的过程和机理,体验有机合成的魅力。     

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.     

AuCl3-Catalyzed Ring-Closing Carbonyl–Olefin Metathesis

Compared with the ripeness of olefin metathesis, exploration of the construction of carbon–carbon double bonds through the catalytic carbonyl–olefin metathesis reaction remains stagnant and has received scant attention. Herein, a highly efficient AuCl₃-catalyzed intramolecular ring-closing carbonyl–olefin metathesis reaction is described. This method features easily accessible starting materials, simple operation, good functional-group tolerance and short reaction times, and provides the target cyclopentenes, polycycles, benzocarbocycles, and N-heterocycle derivatives in good to excellent yields.