Ring-rearrangement Metathesis Research Articles

Ring‐Rearrangement Metathesis

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of N-heterocyclic compounds via ene–yne metathesis reactions

Propargylamino and allylamino derivatives of cyclohexene and norbornene were subjected to tandem metathesis reactions with first and second generation Grubbs' catalysts 1 and 2. Results show that the method is compatible with suitably protected nitrogen-containing compounds. Cyclohexenes gave intriguing results in terms of the possibility to perform ring rearrangement metathesis (RRM) reactions, showing a difference with the analogous allyl and propargyl ether substrates.

Deactivation of Ruthenium Olefin Metathesis Catalysts through Intramolecular Carbene–Arene Bond Formation

for olefin metathesis have been reported, for which strikingly different influences of the ligands on the efficiency of C C bond formation have been observed. For example, notable effects have been found in the class of alkoxy benzylidene ligands first introduced by Hoveyda and coworkers. Phosphine-free complexes such as the secondgeneration Hoveyda–Grubbs catalyst (4 ; IMesH2= 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene) are especially wellsuited for cross metathesis with electron-deficient olefins such as a,b-unsaturated nitriles. The stability and the initiation rate of the precatalyst could be tuned by steric and electronic effects of the substituents. Additional intramolecular interactions of functional groups or atoms with the metal center have been reported for some ligands. 6] Grubbs and co-workers recently found an accelerating effect in olefin metathesis through fluorine– ruthenium interaction. Besides knowledge of such ligand and substituent effects, an understanding of catalyst decomposition and transformation to catalytically inactive ruthenium species is of major importance for the rational design and improvement of metathesis catalysts. Fundamental studies have been presented by Grubbs and co-workers and by Dinger and Mol. Herein, we report a novel deactivation reaction pathway transforming active ruthenium catalysts with alkoxy benzylidene ligands into catalytically inactive carbene complexes. During our study of diastereoselective ring rearrangement metathesis reactions (dRRM), we found that the neutral ligand that remains on the metal center has a pronounced effect on conversion and diastereoselectivity. While only moderate diastereoselectivities could be seen for the firstgeneration catalysts (1, 3), the sterically more demanding and more active second-generation catalysts (2, 4) led to significantly higher selectivities. Thus, we focused on the development of a bulky ruthenium carbene complex to increase the diastereoselective interaction between the olefine moiety and the catalytically active ruthenium species. To do this, we connected the N-aryl substituent with the N-heterocyclic carbene (NHC) through a C2 unit. Unlike in 2 or 4, the aromatic moiety in this new ruthenium complex (5, Scheme 1) should exert a much stronger steric influence on the ruthenium alkylidene moiety through torsion of approximately 458 and hindered rotation. The synthesis of the NHC ligand started from commercially available 2,2’-biquinoline (6). The first step was hydration to octahydrobiquinoline; the result of the hydration was strongly dependent on the catalyst system. PtO2 and H2 under ambient pressure led to the formation of a 3:1 mixture of the meso and racemic forms. Simple chromatography on silica gel

Ring Rearrangement Metathesis of Substituted 2‐Aminonorbornenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Ring‐Rearrangement Metathesis

Ring-rearrangement metathesis (RRM) refers to the combination of several metathesis transformations into a domino process, in which an endocyclic double bond of a cycloolefin reacts with an exocyclic alkene. RRM has proven to be a powerful method for the rapid construction of complex structures. The extension of the basic ring-opening-ring-closing metathesis process by further metathesis steps as well as an examination of the driving forces, limits, scope, recent advantages, and future perspectives of these domino sequences is presented with various examples, thus reflecting the high efficiency and utility of RRM in organic synthesis.

Ring-Rearrangement Metathesis of Substituted 2-Aminonorbornenes

In this report we describe the ring-rearrangement metathesis of 2-aminonorbornene derivatives. Ail efficient ruthenium-catalysed metathesis reaction Occurs with a wide range of pendent alkenes and alkynes to generate bicyclic amines and amides.

Synthesis of cis-Fused Pyranopyran and Pyranopyridine Templates by Ring Rearrangement Metathesis

A short, racemic and multigram scale synthesis of two novel templates is described. The key steps of the synthesis are ring rearrangement metathesis of strained tropane-derivatives into cis-fused pyranopyrans and pyranopyridines and subsequent functionalisation via cross metathesis and stereoselective dihydroxylation.

Catalytic enantioselective total synthesis of (+)-dumetorine by ring-rearrangement metathesis

A concise, enantioselective synthesis of (+)-dumetorine is described, giving the natural product in six steps and a 27% overall yield from a readily available precursor. Among the key steps used, the synthesis entails a high-yielding ring-rearrangement metathesis (RRM), using the commercially available first generation Grubbs catalyst 2 in combination with Ti(O i–Pr) 4 as a co-catalyst. This constitutes the first enantioselective total synthesis of the alkaloid from a known chiral intermediate, and hence a confirmation of its absolute stereochemistry.

A Concise Synthesis of (‐)‐Centrolobine via a Diastereoselective Ring Rearrangement Metathesis—Isomerization Sequence.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

"Ring Closing Metathesis of Substrates Containing more than two C-Cdouble Bonds: Rapid Access to Functionalized Heterocycles"

In most cases where ring closing metathesis is applied to the synthesis of heterocycles, α,ω-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. Keywords: ring rearrangement metathesis, N-heterocyclic carbene, camphor sulfonic acid, Polyheterocycles, erythravine, carbohydrate templates, glycosidase inhibitor

Diastereoselective Ring‐Rearrangement Metathesis

A new stereocenter is formed by ring-rearrangement metathesis (RRM), which has now been extended to diastereoselective processes. Selectivities are catalyst- and substrate-dependent. In these conversions yielding carbo- and heterocycles, d.r. values of up to 14:1 were obtained. For example, cyclooctadiene 1 was converted into piperideine 2 at room temperature and with high diastereoselectivity (Ts=toluene-4-sulfonyl).

A concise synthesis of (−)-centrolobine via a diastereoselective ring rearrangement metathesis–isomerisation sequence

A total synthesis of (-)-centrolobine (1) based on a diastereoselective ring rearrangement metathesis-double bond isomerisation sequence and a one-pot cross metathesis-hydrogenation procedure is described.

A Concise Sequential Photochemical‐Metathesis Approach for the Synthesis of (+)‐Castanospermine and Possible Uniflorine‐A Stereoisomers.

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Ring-rearrangement metathesis of bicyclic amino acid derivatives

In this letter, we describe the ring-rearrangement metathesis (RRM) of bicyclic amino acid derivatives. The procedure is of use for the synthesis of constrained amino acid and peptide derivatives with potential as reverse-turn inducers.

Ring Rearrangement Metathesis (RRM): A New Concept in Piperidine and Pyrrolidine Synthesis

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A concise sequential photochemical-metathesis approach for the synthesis of (+)-castanospermine and possible uniflorine-A stereoisomers

A recently developed strategy for polyhydroxylated indolizidine ring construction has been applied to the synthesis of (+)-castanospermine and possible isomers of uniflorine-A. The routes to these targets rely on the use of the earlier discovered photocyclization reaction of pyridinium perchlorate in a concise route for preparation of a key N-allylacetamidocyclopentendiol intermediate. Ring rearrangement metathesis of this substance gives an allyl-tetrahydropyridine, which is then transformed to the targets by execution of regio- and stereo-controlled hydroxylation processes followed by indolizidine ring construction.

Total Synthesis of (+)-trans-195A

[reaction: see text] The first enantioselective synthesis of (+)-trans-195A is described. The structure has been constructed by ring-rearrangement metathesis (RRM) and zirconium-mediated Negishi-coupling, used for the first time to prepare 6,6-membered heterocycles, as key steps. By comparison of the synthesized material with the isolated natural product, the absolute configuration of natural trans-195A was determined to be (2R,4aS,5R,8aS)-(-).

Stereoselective Synthesis of Polyhydroxylated Indolizidines Based on Pyridinium Salt Photochemistry and Ring Rearrangement Metathesis.

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Concise Enantioselective Synthesis of (‐)‐Lasubine II.

Abstract An enantioselective synthesis of the quinolizidine alkaloid (−)-lasubine II 1 is reported. Two different pathways to the key intermediate 2 are described. The first case involving a sequence of ring rearrangement metathesis (RRM), simple functional group interconversion operations, followed by a stereoselective cross metathesis (CM) and in the second case a domino ring opening-/ring closing-/cross metathesis step is involved. In both cases, following the metathesis reactions, exclusively the E-isomer was obtained. The final cyclisation towards the quinolizidine skeleton is achieved by an intramolecular Michael reaction. This concept represents the first example of a highly stereoselective RRM-CM combination in the synthesis of a natural product.

A Ring‐Rearrangement Metathesis Approach Toward the Synthesis of Cyclopenta‐ and Cyclohexa[c]indene Systems.

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