Self-selection in olefin cross-metathesis: the effect of remote functionality

Olefin cross-metathesis (CM) is potentially an attractive method for generating dynamic combinatorial libraries (DCLs). In order for the CM reaction to be useful for DCL production, the course of the reaction and product distribution must be relatively insensitive to functionality remote from the reacting centers. We report on the CM of a series of allyl- and homoallylamides that are strongly dependent on remote functionality. This includes an unusual example of a cis-selective CM. [Reaction: see text]     

Synthesis of symmetrical trisubstituted olefins by cross metathesis

[reaction: see text] Trisubstituted alkenes have been prepared via intermolecular olefin cross-metathesis (CM) between alpha-olefins and symmetrically 1,1-disubstituted olefins using an imidazolylidene ruthenium benzylidene complex. Of particular interest is the synthesis of isoprenoid/prenyl groups by a simple solvent-free CM reaction with isobutylene. In addition, prenyl groups can also be installed by a cross-metathesis of 2-methyl-2-butene with a variety of alpha-olefins at room temperature with low catalyst loadings.     

Highly demanding cross-metathesis in the synthesis of the C16-C30 fragment of dolabelide C

A highly demanding cross-metathesis (CM) reaction for the formation of the C24-C25 trisubstituted olefin of dolabelide C has been optimized. A difference in reactivity between the E and Z enone isomers in this reaction was uncovered, and the selection of the Z isomer of the starting enone was critical for the success of the cross-metathesis. Application to the synthesis of the C16-C30 fragment of dolabelide C is reported.     

Cross-metathesis between alpha-methylene-gamma-butyrolactone and olefins: a dramatic additive effect

[reaction: see text] Olefin cross-metathesis between alpha-methylene-gamma-butyrolactone and terminal olefins is described. Moderate to excellent yields of alpha-alkylidene-gamma-butyrolactones were obtained with high E-stereoselectivity in the presence of low catalyst loading in refluxing CH2Cl2. In addition, the use of various additives was found to have a dramatic effect on the efficiency of the cross-metathesis (CM) process by circumventing the formation of the isomerized byproduct.     

Concise enantioselective synthesis of 3,5-dialkyl-substituted indolizidine alkaloids via sequential cross-metathesis-double-reductive cyclization

An efficient stereoselective synthesis of two 3,5-dialkyl-substituted indolizidine alkaloids is reported. The convergent syntheses are based on a novel sequence of a cross-metathesis (CM) reaction of an alpha,beta-unsaturated ketone and a chiral homoallylic amine followed by a domino reaction involving hydrogenation, N-deprotection, and two diastereoselective reductive aminations. Our concept presents one of a few examples of a highly selective CM reaction in the synthesis of a natural product.     

Synthesis of unsaturated amino alcohols through unexpectedly selective Ru-catalyzed cross-metathesis reactions

[reaction: see text]. A two-step synthesis of N-protected unsaturated amino alcohols is disclosed that relies on an unexpectedly selective cross-metathesis (CM) involving allyl cyanide and pent-4-en-1-ol. The solution concentration and the identity of the Ru complex used are critical to the selectivity and efficiency of CM reactions. The intermediate obtained by CM is converted efficiently to the final desired products through a one-pot nitrile reduction/amine protection procedure.     

Late-stage Modification of Cage Diones by Tandem Metathesis

Herein, we report the application of tandem ring-opening cross-metathesis (ROCM) and tandem ring-opening cross-metathesis followed by cross-metathesis (ROCM/CM) in highly strained diastereomeric heptacyclic cage diones (HCCD's) catalyzed by ruthenium catalysts. These caged diastereomeric compounds have a high degree of ring strain as well as steric congestion. Therefore, the present work related to ROCM is unique and intricate as compared to simple norbornene derivatives. It is useful to prepare new hexacyclic cage derivatives suitable for high-energy density materials. The synthetic strategy of starting cage compounds features the Diels-Alder reaction, and [2+2] photocycloaddition as key steps.     

A formal synthesis of SCH 351448

An efficient formal synthesis of SCH 351448 was accomplished through the tandem cross-metathesis (CM)/oxa-Michael, the 1,4-syn aldol, the tandem oxidation/oxa-Michael, and the Suzuki coupling reaction.     

Concise total synthesis of (+)-carpamic acid

We report herein an efficient enantioselective synthesis of (+)-carpamic acid, with nine steps as the longest linear sequence, the key strategy being based on a novel sequence of a cross-metathesis (CM) reaction and a subsequent cyclizing reductive amination to form the piperidine ring.     

Selective formation of dihydropyran derivatives by a tandem domino ring-closing metathesis/cross-metathesis

A ring-closing metathesis (RCM)/cross-metathesis (CM) domino reaction has been applied to esters and unsymmetrical ether prepared from 1,5-hexadien-3-ol. For the first time, dihydropyran derivatives have been obtained via a regioselective cyclization. This reaction was performed in high yield and E stereoselectivity.     

Experimental and theoretical study on the olefin metathesis of alkenyl Baylis-Hillman adducts using second-generation Grubbs catalyst

[reaction: see text] We have investigated the olefin metathesis from alkenyl Baylis-Hillman adducts using second-generation Grubbs catalyst. In the experiment, the ring-closing metathesis (RCM) product could not be found, while the cross-metathesis (CM) products were found. The computational studies provided consistent explanations for the experimental result. The most limiting factor for the RCM process using second-generation Grubbs catalyst is caused by the high strain and steric effect in the metallacyclobutane intermediates.     

Diversity-oriented approach to macrocyclic cyclophane derivatives by Suzuki-Miyaura cross-coupling and olefin metathesis as key steps

Palladium-catalyzed Suzuki-Miyaura (SM) cross-coupling reaction with allylboronic acid pinacol ester and titanium assisted cross-metathesis (CM)/ring-closing metathesis (RCM) cascade has been used to synthesize macrocyclic cyclophane derivatives.     

An olefin cross-metathesis approach to vinylphosphonate-linked nucleic acids

[reaction: see text]. The synthesis of vinylphosphonate-linked nucleotide dimers has been achieved using an olefin cross-metathesis (CM) reaction as a key step. The 1,3-dimesityl-4,5-dihydroimidazol-2-ylidine-containing catalyst 5 (Grubbs' second-generation catalyst) was found to be the superior catalyst for this transformation. Both metathesis partners were readily available using known methodology, and the vinylphosphonate-linked dimer was produced with high levels of (E)-selectivity (>20:1) in 58% yield (70% based on recovered starting material).     

Total synthesis of (+)-phomopsolide C by ring-size selective ring-closing metathesis/cross-metathesis

[reaction: see text]A new strategy for the synthesis of chiral 6-substituted 5,6-dihydro-5-hydroxypyran-2-ones by ring-size selective ring-closing metathesis (RCM) and its application to a short total synthesis of (+)-phomopsolide C are described. The key bond-forming reactions in this approach are a chemoselective cross-metathesis (CM) and RCM.     

Divergent total synthesis of aspinolides B,E and J

Stereoselective total synthesis of aspinolides B, E and J, naturally occurring 10-membered lactones, were accomplished by divergent strategies starting from the commercially available 2,3-O-isopropylidene-d-ribose and methyl d-lactate. The synthesis features rapid access to the both key fragments from chiral pool and the formation of 10-membered ring lactones containing trans double bond employing cross-metathesis reaction (CM) and intramolecular Shiina macrolactonization.     

Olefin cross-metathesis of a vinyl-terminated self-assembled monolayer (SAM) on Au(111): electrochemical study using a ferrocenyl redox center

Self-assembled thiol monolayers bound to single-crystal Au(111) surfaces containing a terminal olefin have been prepared and used to monitor electrochemically the cross-metathesis (CM) between the surface and an olefin-terminated ferrocenyl (Fc) derivative from solution over time. Mixed SAM surfaces were prepared by first adsorbing a diluent for 2 days followed by the olefinic alkanethiol for known adsorption time intervals; three diluents of varying length were used. The oxidation peak areas from the voltammetry show the CM reaction yields a maximum amount of product at 100-150 min. Beyond this time, thiol desorption is apparent and the Fc oxidation peaks diminished. A kinetic simulation of the interfacial reactions involving CM and desorption reactions are described and aided in the interpretation of the voltammetric responses. The length of the diluent and the coverage of surface olefins were important factors in limiting undesirable self-CM reactions on the surface, and a model of the relationship between the diluent and surface concentration of olefin is described. This study shows that attention to monolayer formation and reaction conditions are important parameters when maximizing CM yields on surfaces.     

Olefin cross-metathesis for the synthesis of heteroaromatic compounds

The olefin metathesis reaction has underpinned spectacular achievements in organic synthesis in recent years. Arguably, metathesis has now become the foremost choice for a carbon-carbon double bond disconnection. Despite this general utility, de novo routes to heteroaromatic compounds using the cross-metathesis (CM) reaction have only recently emerged as an efficient strategy. This approach allows a convergent union of simple, functionalised, three- to four-carbon olefinic core building blocks, to generate furans, pyrroles and pyridines with a high degree of control of substitution pattern in the product.     

Stereoselective total synthesis of cryptopyranmoscatone A1

The first total synthesis of cryptopyranmoscatone A1 isolated from Cryptocarya moschata has been accomplished from 3,4,6-tri-O-acetyl-d-glucal. In addition to the RCM and cross-metathesis (CM) reactions, the synthesis features a highly diastereoselective Brown’s allylation reaction and sets the absolute stereochemistry of the natural product.     

Cross-metathesis of α-methylene-β-lactams: the first tetrasubstituted alkenes by CM

α-Alkylidene-β-lactams have been prepared in good to excellent yields by olefin cross-metathesis. Electron-poor α-methylene-β-lactams undergo cross-metathesis more rapidly and efficiently than more electron-rich analogs. Significantly, tetrasubstituted alkenes have for the first time been accessed by CM reactions.