Synthesis of six-membered cyclic siloxanes via enyne metathesis with a ruthenium catalyst generated in situ

The catalytic system in situ generated by combination of [RuCl₂(p-cymene)]₂ as a ruthenium source, 1,3-bis(mesityl)imidazolinium chloride (MesH₂ImCl) as a bulky electron-releasing carbene precursor and cesium carbonate as a base, is shown to be an efficient catalyst for the metathesis reaction of propargylic allylsilyl ethers R¹---CCCR₂---O---SiMe₂---CH₂CH=CH₂. The metathesis products, the cyclic siloxanes, were obtained after complete conversion of the enynes in 67–87% isolated yields. These six-membered ring compounds contain the 1,3-diene unit that is used in Diels–Alder reaction and give access to heterobicyclic derivatives. The resulting cyclic siloxanes are selectively opened under oxidative conditions with H₂O₂ to afford allylic diols, with fluoride to form conjugated triene and under hydrogenation conditions with Pd/C catalyst to give a tetrasubstituted alkene.     

On the mechanism of a double ring-closing metathesis reaction

A detailed study of the steps involved in the double ring-closing metathesis reaction of 2 to 3 has been carried out. Both the selectivity and mechanism were affected by choice of catalyst.     

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.     

Microwave-assisted ring-closing metathesis of diallylamines: a rapid synthesis of pyrrole and pyrroline derivatives

The ring-closing metathesis (RCM) reactions of diallylamines occurred under controlled microwave irradiation. In addition to the high reaction rate, the key features of the reaction are that it can be carried out without deactivation of the substrates and without the use of Lewis acids.     

Absence of the Thorpe-Ingold Effect by gem-Diphenyl Groups in Ring-Closing Enyne Metathesis

In tandem ring-closing metathesis of alkynyl silaketals containing two different tethered olefins, the gem-dimethyl group showed the expected Thorpe-Ingold effect, thereby giving good level of group selectivity. Unexpectedly, however, the corresponding gem-diphenyl group did not show any Thorpe-Ingold effect for the ring-closure reaction.     

The first example of ring-closing olefin metathesis of dehydroamino acids: an application to the synthesis of azabicyclo[X.Y.0]alkanes

The first example of ring-closing metathesis reaction of dehydroamino acids using ruthenium-based catalyst leading to the azabicyclo[X.Y.0]alkanes has been demonstrated. A preliminary investigation into the scope and limitations of the method will be presented.     

Ring-closing metathesis as a tool for the efficient preparation of chiral spirocyclic ethers from homoallylic alcohols

The preparation of chiral spirocyclic ethers via allylic etherification/olefin metathesis of homoallylic alcohols is investigated. This reaction sequence transforms the enantiopure substrate alcohols, synthesized by a one-pot asymmetric rhodium-catalyzed conjugate addition/metal-mediated allylation procedure, into the desired spiro ethers with full conversions and in excellent isolated yields. The synthetic sequence provides an efficient means for a rapid construction of functionalized spiro ethers in a stereoselective manner.     

A novel synthesis of substituted quinolines using ring-closing metathesis (RCM): its application to the synthesis of key intermediates for anti-malarial agents

A method for synthesizing substituted quinolines using ruthenium-catalyzed ring-closing metathesis as a key step has been developed. Substituted 1,2-dihydroquinolines, 4-silyloxy-1,2-dihydroquinoline and 4-methoxy-1,2-dihydroquinoline, were successfully synthesized in excellent yields via ene-ene metathesis and silyl or alkyl enol ether-ene metathesis, respectively. The synthetic intermediates of the antimalarial agents quinine, chloroquine, and PPMP-quinine hybrid were efficiently synthesized by this methodology.     

Suzuki-Miyaura cross-coupling and ring-closing metathesis: a strategic combination to the synthesis of indeno[1,2-c]isoquinolin-5,11-diones

A variety of diversely substituted isoindeno[1,2-c]isoquinolin-5,11-diones has been readily assembled through a sequence involving a Suzuki-Miyaura cross-coupling reaction with enol phosphates combined with a ring-closing metathesis (RCM) reaction. Intramolecular carbocationic annulation reaction and ultimate oxidation of a latent hydroxyl functionality completed the synthesis of the target titled compounds.     

Synthesis and Catalytic Activity of a Two-core Ruthenium Carbene Complex: a Unique Catalyst for Ring Closing Metathesis Reaction

The reaction of a ruthenium carbide complex RuCl2(C:)(PCy3)2 with [H(Et2O)x]+[BF4]– at a molar ratio of 1:2 produced a two-core ruthenium carbene complex, {[RuCl(=CHPCy3)(PCy3)]2(μ-Cl)3}+·[BF4]–, in the form of a yellow-green crystalline solid in a yield of 94%. This two-core ruthenium complex is a selective catalyst for ring closing metathesis of unsubstituted terminal dienes. More importantly, no isomerized byproduct was observed for N-substrates when the two-core ruthenium complex was used as the catalyst at an elevated temperature(137 °C), indicating that the complex is a chemo-selective catalyst for ring closing metathesis reactions.     

Tandem aza-Claisen rearrangement and ring-closing metathesis reactions: the stereoselective synthesis of functionalised carbocyclic amides

A one-pot, tandem process has been developed for the efficient synthesis of functionalised carbocyclic amides. A substituted cyclopentenyl trichloroacetamide was synthesised using a tandem thermal aza-Claisen rearrangement and RCM process, while an analogous cyclohexenyl trichloroacetamide was generated with high diastereoselectivity using a tandem MOM-ether directed metal-catalysed aza-Claisen rearrangement and RCM process.     

Ring-closing metathesis for the synthesis of heteroaromatics: evaluating routes to pyridines and pyridazines

Ring-closing olefin metathesis (RCM) has been applied to the efficient synthesis of densely and diversely substituted pyridine and pyridazine frameworks. Routes to suitable metathesis precursors have been investigated and the scope of the metathesis step has been probed. The metathesis products function as precursors to the target heteroaromatic structures via elimination of a suitable leaving group, which also facilitates earlier steps by serving as a protecting group at nitrogen. Further functionalisation of the metathesis products is possible both prior to and after aromatisation. The net result is a powerful strategy for the de novo synthesis of highly substituted heteroaromatic scaffolds.     

Ring-closing metathesis as a new methodology for the synthesis of monomeric flavonoids and neoflavonoids

Basic flavonoid (flavene) and neoflavonoid (neoflavene) skeletons were successfully synthesized using ring-closing metathesis, showing that this methodology can be used as a central synthetic tool for the synthesis of at least two of the three basic flavonoid classes.     

From building block to natural products: a short synthesis and complete NMR spectroscopic characterization of (±)-anatabine and (±)-anabasine

A short and straightforward synthesis of the racemic tobacco alkaloids anatabine and anabasine in five and six steps, respectively, from 3-pyridinecarboxaldehyde utilizing Barbier-type Zn-mediated allylation and ring-closing olefin metathesis, as the key steps, is reported. Additionally, a complete NMR spectroscopic analysis of the final products is carried out and full assignment of the NMR spectra of anatabine and anabasine with accurate coupling constants is accomplished and reported here for the first time.     

Ring-closing olefin metathesis in the aqueous phase of amphiphilic conetworks consisting of fluorophilic and hydrophilic compartments

A Grubbs-Hoveyda-Type metathesis catalyst bearing a tris(perfluoroalkyl)silyl tag was immobilized in the fluorophilic phase of amphiphilic conetworks (APCNs). This catalytic system was applied to ring-closing metathesis (RCM) reactions in aqueous media. Different substrates were evaluated and with 10 mol% of catalyst at 60 °C good conversions were observed. Reuse of the catalytic system was possible, but resulted generally in lower conversions.     

Total synthesis of aspinolide B: a ring-closing metathesis approach

A highly convergent stereoselective total synthesis of aspinolide B, a 10-membered lactone is described. The key step includes a ring-closing metathesis reaction to construct the 10-membered ring and the E—olefinic moiety. d-Mannitol was used as a chiral pool material for the construction of the key fragments—the olefinic acid and the olefinic alcohol moieties.     

Formal synthesis of brivaracetam: A key to construct the pyrrolidone scaffold using Pd-catalyzed oxidative cyclization and ring-closing metathesis reaction

A short and efficient synthetic approach for brivaracetam has been accomplished via two different routes which utilize Pd-catalyzed oxidative cyclization and ring-closing metathesis (RCM) as the key reaction. These two routes are novel, simple, scalable and rely on (E)-pent-2-en-1-ol and valeraldehyde as a commercially available starting material to yield brivaracetam with good overall yield.     

A ring-closing metathesis based synthesis of bicyclic nucleosides locked in S-type conformations by hydroxyl functionalised 3′,4′-trans linkages

A [4.3.0]bicyclic nucleoside that contains an unsaturated hydroxylated 3′,4′-trans linkage has been efficiently synthesised. Thus, from diacetone-d-glucose as the starting material, stereoselective Grignard reactions for the introduction of allyl groups, a nucleobase coupling and, subsequently, a ring-closing metathesis (RCM)-reaction were applied as the key reactions. The cyclohexene moiety introduced in this nucleoside reveals a large potential for further derivatisation, and as the first example, a stereoselective dihydroxylation followed by deprotection afforded a multihydroxylated bicyclic nucleoside. The configuration and conformational behaviour was determined by NMR spectroscopy and ab initio calculations, and both this bicyclic nucleoside and its unsaturated analogue were found to be strongly restricted in S-type conformations.     

A quadruple ring-closing metathesis reaction in the synthesis of bis-spirocyclic compounds: extending the scope of metathesis chemistry

The first example of a quadruple ring-closing metathesis reaction is reported. The reaction of the C2 symmetric octaene 3 afforded bis-spirocyclic compounds in high yield.     

New synthesis of carbazole-1,4-quinone using a tandem ring-closing metathesis and dehydrogenation reaction under oxygen atmosphere, and its application to the synthesis of murrayaquinone A

A tandem ring-closing metathesis and dehydrogenation reaction under oxygen atmosphere was newly developed to the synthesis of carbazole-1,4-quinones. This new tandem reaction was applied to the synthesis of murrayaquinone A in four steps.