Catalysts For Ring-closing Metathesis Research Articles

Self-Supported Oligomeric Grubbs/Hoveyda-Type Ru−Carbene Complexes for Ring-Closing Metathesis

On the basis of the release-return metathesis mechanism, self-supported oligomeric Grubbs/Hoveyda-type Ru-carbene complexes have been designed and synthesized as a new type of recoverable catalyst for ring-closing metathesis. The catalytic activities of the self-supported oligomeric Ru-carbene complex in ring-closing metathesis are comparable to those of their homogeneous counterpart as they work homogeneously and are recovered heterogeneously.

Facile one-step synthesis of bis(NHC) ruthenium benzylidene catalyst for ring-closing metathesis

Bis(NHC) ruthenium benzylidene complex (H 2IMe) 2(Cl) 2Ru CHPh ( 9) [H 2IMe = 1,3-bis(2,6- dimethylphenyl)-4,5-dihydroimidazol-2-ylidene] was synthesized facilely by one-step reaction of (PPh 3) 2(Cl) 2Ru CHPh ( 7) with N-heterocyclic carbene (NHC) H 2IMe ( 6). Complex 9 proved to exhibit remarkable catalytic activity for ring-closing metathesis (RCM) reaction at increased temperature.

Activated pyridinium-tagged ruthenium complexes as efficient catalysts for ring-closing metathesis

New pyridinium-tagged ruthenium catalysts have been synthesised to perform olefin metathesis in several media including both organic and aqueous solvents and room temperature ionic liquids (RTILs). High activity was obtained in the ring-closing metathesis (RCM) of a variety of di- or tri-substituted and/or oxygen-containing dienes. However, only fair levels of recycling combined with low to moderate residual ruthenium levels (25–173 ppm) have been observed showing clearly the difficulty of associating high activity and recyclability.

Ring‐Closing Metathesis as a Basis for the Construction of Aromatic Compounds

The use of metathesis, especially in the context of ring-closing metathesis (RCM) to form five- and six-membered rings, is widespread in organic chemistry today. However, there are surprisingly few examples of the reaction being used to form aromatic compounds. The central place of aromatic compounds in both medicinal chemistry and natural products synthesis, coupled with the efficiency and functional group tolerance of RCM catalysts, means that there is now an interesting opportunity to use RCM for the synthesis of arenes. Although the formation of an aromatic compound was viewed in many early examples as an undesirable degradation product, several rationally designed methods towards the preparation of aromatic compounds by RCM have recently been developed.

Novel Ruthenium‐Based Metathesis Catalysts Containing Electron‐Withdrawing Ligands: Synthesis, Immobilization, and Reactivity.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Novel Ruthenium-Based Metathesis Catalysts Containing Electron- Withdrawing Ligands: Synthesis, Immobilization, and Reactivity

The syntheses and reactivity of seven different ruthenium-based metathesis catalysts are described. Ru(CF3COO)2(PCy3)(=CH-2-(2-PrO)C6H4) (1), Ru(CF3COO)2(1,3-dimesityldihydroimidazolin-2-ylidene)(=CH-2-(2-PrO)C6H4) (2), and Ru(CF3COO)2(PCy(3))(1,3-dimesityldihydroimidazolin-2-ylidene)(=CHC6H5) (3) were prepared via chlorine exchange by reacting RuCl2(PCy3)2(=CH-2-(2-PrO)C6H4), RuCl2(1,3-dimesityldihydroimidazolin-2-ylidene)(=CH-2-(2-PrO)C6H4), and RuCl2(PCy3)(1,3-dimesityldihydroimidazolin-2-ylidene)(=CHC6H5), respectively, with silver trifluoroacetate (Cy =cyclohexyl). In analogy, Ru(CF3CF2COO)2(1,3-dimesityldihydroimidazolin-2-ylidene)(=CH-2-(2-PrO)C6H4) (4) and Ru(CF3CF2CF2COO)2(1,3-dimesityldihydroimidazolin-2-ylidene)(=CH-2-(2-PrO)C6H4) (5) were prepared from RuCl2(1,3-dimesityldihydroimidazolin-2-ylidene)(=CH-2-(2-PrO)C6H4) via reaction with CF3CF2COOAg and CF3CF2CF2COOAg, respectively. Ru(C6F5COO)2(1,3-dimesityldihydroimidazolin-2-ylidene)(=CH-2-(2-PrO)C6H4) (6) and Ru(C6F5O)2(1,3-dimesityldihydroimidazolin-2-ylidene)(=CH-2-(2-PrO)C6H4) (7) were prepared from RuCl2(1,3-dimesityldihydroimidazolin-2-ylidene)(=CH-2-(2-PrO)C6H4) via reaction with C6F5COOTl and C6F5OTl, respectively. Supported catalysts Ru(PS-DVB-CH2OOCCF2CF2CF2COO)(CF3COO)(PCy3)(1,3-dimesityldihydroimidazolin-2-ylidene)(=CHC6H5) (8), Ru(PS-DVB-CH2OOCCF2CF2CF2COO)(CF3COO)(PCy3)(=CH-2-(2-PrO)C6H4) (9), and Ru(PS-DVB-CH2OOCCF2CF2CF2COO)(CF3COO)(1,3-dimesityldihydroimidazolin-2-ylidene)(=CH-2-(2-PrO)C6H4) (10) were synthesized by reaction of RuCl2(PCy3)(1,3-dimesityldihydroimidazolin-2-ylidene)(=CHC6H5), RuCl2(PCy3)(=CH-2-(2-PrO)C6H4), and RuCl2(1,3-dimesityldihydroimidazolin-2-ylidene)(=CH-2-(2-PrO)C6H4), respectively, with a perfluoroglutaric acid-derivatized poly(styrene-co-divinylbenzene) (PS-DVB) support (silver form). Halogen exchange in PCy3-containing systems had to be carried out in dichloromethane in order to suppress precipitation of AgCl.PCy3. The reactivity of all new catalysts in ring-closing metathesis (RCM) of hindered electron-rich and -poor substrates, respectively, at elevated temperature (45 degrees C) was compared with that of existing systems. Diethyl diallylmalonate (DEDAM, 11), diethyl allyl(2-methylallyl)malonate (12), N,N-diallyl-p-toluenesulfonamide (13), N-benzyl-N-but-1-en-4-ylbut-2-enecarboxylic amide (14), and N-allyl-N-(1-carboxymethyl)but-3-en-1-yl-p-toluenesulfonamide (15) were used as educts. Supported catalysts were prepared with high loadings (2.4, 22.1, and 160 mg of catalyst/g PS-DVB for 8, 9, and 10, respectively). Catalyst 8 showed higher and catalysts 9 and 10 sowed significantly reduced activities in RCM compared to their homogeneous analogues. Thus, with 8, turnover numbers (TONs) up to 4200 were realized in stirred-batch (carousel) RCM experiments. To elucidate the nature of the bound species, catalysts 8-10 were subjected to 13C- and 31P-MAS NMR spectroscopy. These investigations provided evidence for the proposed structures. Leaching of ruthenium into the reaction mixture was low, resulting in ruthenium contents <85 ppb (ng/g) in the final RCM-derived products.

An ionic liquid-tagged second generation Hoveyda–Grubbs ruthenium carbene complex as highly reactive and recyclable catalyst for ring-closing metathesis of di-, tri- and tetrasubstituted dienes

A second generation Hoveyda–Grubbs ruthenium carbene complex bearing an ionic liquid tag was prepared and shown to be a highly reactive catalyst for the ring-closing metathesis of di-, tri- and tetrasubstituted diene and enyne substrates in minimally ionic solvent systems ([Bmim]PF 6/CH 2Cl 2, 1:9–1:1 v/v). Both the catalyst and the ionic liquid can be conveniently recycled and repeatedly reused (up to 17 cycles) with only a very slight loss of activity. The ionic liquid tag is crucial to the high level of recyclability of the catalyst since the original second generation Grubbs and Hoveyda–Grubbs catalysts rapidly lose their activity when recycled in the ionic liquid layer.

Design, synthesis, and conformational analysis of eight-membered cyclic peptidomimetics prepared using ring closing metathesis

As part of a program to identify novel scaffolds that adopt defined secondary structure when incorporated into peptides, we have designed and prepared a library of constrained eight-membered ring lactams based upon 7-amino-8-oxo-1,2,3,6,7-pentahydroazocine-2-carboxylic acid. Ring closing metathesis (RCM) was employed as the key step, proceeding in high yields to afford the Z olefin. In this reaction sequence, the first generation benzylidene ruthenium RCM catalyst was superior to the second-generation imidazoline catalyst, which gave extensive oligomerization at higher concentrations. Conformational analysis of the 2 S,7 S and 2 R,7 S stereoisomers revealed that the 2 R,7 S isomer is a Type VIa β-turn in the solid state (X-ray crystal structure) and in water (NMR analysis). The Type VIa β-turn is relatively rare, typically bearing the cis amide bond found in proline-containing sequences. The 2 S,7 S diastereomer has an extended geometry of the pendent amide chains. The corresponding saturated derivatives (7-amino-8-oxoazocane-2-carboxylic acid) were also synthesized and investigated. The 2 S,7 S azocane bears an extended geometry and mimics the C + conformer of ox-[Cys-Cys], found in a variety of naturally occurring peptides. The scaffolds described here are useful for the design of constrained peptidomimics with defined secondary structure.

Eta6-mesityl,eta1-imidazolinylidene-carbene-ruthenium(II) complexes: catalytic activity of their allenylidene derivatives in alkene metathesis and cycloisomerisation reactions.

The reaction of electron-rich carbene-precursor olefins containing two imidazolinylidene moieties [(2,4,6-Me(3)C(6)H(2)CH(2))NCH(2)CH(2)N(R)Cdbond;](2) (2a: R=CH(2)CH(2)OMe, 2 b R=CH(2)Mes), bearing at least one 2,4,6-trimethylbenzyl (R=CH(2)Mes) group on the nitrogen atom, with [RuCl(2)(arene)](2) (arene=p-cymene, hexamethylbenzene) selectively leads to two types of complexes. The cleavage of the chloride bridges occurs first to yield the expected (carbene) (arene)ruthenium(II) complex 3. Then a further arene displacement reaction takes place to give the chelated eta(6)-mesityl,eta(1)-carbene-ruthenium complexes 4 and 5. An analogous eta(6)-arene,eta(1)-carbene complex with a benzimidazole frame 6 was isolated from an in situ reaction between [RuCl(2)(p-cymene)](2), the corresponding benzimidazolium salt and cesium carbonate. On heating, the RuCl(2)(imidazolinylidene) (p-cymene) complex 8, with p-methoxybenzyl pendent groups attached to the N atoms, leads to intramolecular p-cymene displacement and to the chelated eta(6)-arene,eta(1)-carbene complex 9. On reaction with AgOTf and the propargylic alcohol HCtbond;CCPh(2)OH, compounds 4-6 were transformed into the corresponding ruthenium allenylidene intermediates (4-->10, 5-->11, 6-->12). The in situ generated intermediates 10-12 were found to be active and selective catalysts for ring-closing metathesis (RCM) or cycloisomerisation reactions depending on the nature of the 1,6-dienes. Two complexes [RuCl(2)[eta(1)-CN(CH(2)C(6)H(2)Me(3)-2,4,6)CH(2)CH(2)N- (CH(2)CH(2)OMe)](C(6)Me(6))] 3 with a monodentate carbene ligand and [RuCl(2)[eta(1)-CN[CH(2)(eta(6)-C(6)H(2)Me(3)-2,4,6)]CH(2)CH(2)N-(CH(2)C(6)H(2)Me(3)-2,4,6)]] 5 with a chelating carbene-arene ligand were characterised by X-ray crystallography.

Synthesis of pyridine fused polycyclic amines using sequential ring-closing metathesis and radical cyclisation reactions

The syntheses of novel pyridine fused polycyclic bridgehead amines are described using sequential ring-closing metathesis (RCM) and 5- exo-trig intramolecular radical cyclisation reactions. Critical to the success of the two sequential steps were the RCM catalyst and/or the nature of the nitrogen atom.

Combining the use of solid-supported transition metal catalysis with microwave irradiation in solution-phase parallel library synthesis.

Microwave heating methods have been combined with the use of solid-supported catalysts to produce small solution-phase libraries of medicinally-relevant compounds. Palladium supported on charcoal (Pd/C) has been used to produce libraries of pyrazole compounds for screening in COX II studies via Suzuki cross coupling reactions, while the same catalyst has been used also to produce styryl-based nAChR compounds using analogous chemistry. Although the reaction substrates are very different (aryl vs. vinyl), this catalyst system provided consistently good and reliable results. The use of a polystyrene-supported Ru catalyst for ring-closing metathesis (RCM) reactions was also evaluated to prepare benzolactam structures for evaluation as factor Xa inhibitors.

Ti–Ru bimetallic complexes: catalysts for ring-closing metathesis

The reaction of the titanocene monophosphanes ( 1– 4) with the dimer [( p-cymene)RuCl 2] 2 gives the heterobimetallic compounds ( p-cymene)[(η 5-C 5H 5)(μ-η 5:η 1-C 5H 4(CR 2) n PR′ 2)TiCl 2]RuCl 2 ( 5– 8). The structure of 8, determined by X-ray diffraction, is reported here. A preliminary assessment of the performance of these complexes in ring-closing metathesis (RCM) revealed an excellent Ti–Ru–allenylidene pre-catalyst 12.

Simply assembled and recyclable polymer-supported olefin metathesis catalysts

Polymer-supported ruthenium catalysts (PCy(3))(2)Ru(=C(H)Ph)Cl(2), (PCy(3))Ru(IMes)(=C(H)Ph)Cl(2), and (PCy(3))Ru(SIMes)(=C(H)Ph)Cl(2), where IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene and SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene, have been prepared and found to be effective "boomerang" catalysts for ring-closing metathesis. They are recyclable, show comparable or better reactivity than their homogeneous counterparts, tolerate functional groups, and perform very well with dienes and moderately well with highly hindered substrates.

α-CF3-Substituted Phosphorus Containing Analogs of α-Amino Acids. Novel Six- and Seven-Membered α-Amino Phosphonates via Ring Closing Metathesis with LnRu=C=C=CR2Precatalyst

α-CF3-substituted α-amino phosphonates with two alkene chains, 1,7-dienes and 1,8-dienes, were obtained by nucleophilic addition to highly electrophilic imines PG-N=C(CF3)P(O)(OR)2. They were treated with the ring closing metathesis catalyst [Ru=C=C=CPh2(Cl)(PCy3)2 (p-cymene)]OTf to give the α-CF3-substituted phosphorus-containing analogs of dehydropipecolinic and tetrahydroazepin-2-carboxylic acids.

(p-cymene)RuLCl2 (L = 1,3-Bis(2,4,6-trimethylphenyl)imidazol-2-ylidene and 1,3-Bis(2,6-diisopropylphenyl)imidazol-2-ylidene) and Related Complexes as Ring Closing Metathesis Catalysts.

(<i>p</i>-cymene)RuLCl₂ (L = 1,3-Bis(2,4,6-trimethylphenyl)imidazol-2-ylidene and 1,3-Bis(2,6-diisopropylphenyl)imidazol-2-ylidene) and Related Complexes as Ring Closing Metathesis Catalysts.

Indenylidene−Imidazolylidene Complexes of Ruthenium as Ring-Closing Metathesis Catalysts

The indenylidene−imidazolylidene complexes of ruthenium (IMes)(PR3)Cl2Ru(3-phenylindenylid-1-ene) and (IPr)(PR3)Cl2Ru(3-phenylindenylid-1-ene) (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, and R= Ph, Cy) were prepared and found to be efficient catalyst precursors for ring-closing metathesis.

Synthesis of Functionalized Polyethers by Ring-Opening Metathesis Polymerization of Unsaturated Crown Ethers

A variety of polyethers were synthesized by a tandem approach incorporating ring-closing metathesis (RCM) followed by ring-opening metathesis polymerization (ROMP) using RuCl2(CHPh)(PCy3)2 (1) as an initiator. Unsaturated crown ether monomers, including a 12-crown-4 analogue (3), a benzocrown ether (8), and a benzocrown ether with a pendent phenylalanine methyl ester (9), were synthesized in good yields using a lithium ion as a template and 1 as a catalyst for RCM. Saponification of 9 afforded the benzocrown phenylalanine carboxylic acid monomer 10. The ROMP of 3, 8, and 9 with 1 as an initiator yielded the homopolymers 11, 12e, and 13e, respectively. The relative concentrations of 3 to 1 were varied to produce 11 with a wide range of molecular weights (Mn from 10 900 to 206 300). Hydrogenation of 11 proceeded quantitatively to yield a saturated polyether. Monomers 8 and 9 were copolymerized with 3 to generate polymers 12a−d and 13a−d, respectively. The copolymer composition corresponded to the feed ratio of the monomers. Crown ether 10 was copolymerized with 3 at a low feed ratio to form the corresponding polyether with pendent amino acids.

(p-cymene)RuLCl2 (L = 1,3-Bis(2,4,6-trimethylphenyl)imidazol-2-ylidene and 1,3-Bis(2,6-diisopropylphenyl)imidazol-2-ylidene) and Related Complexes as Ring Closing Metathesis Catalysts

Complexes of (η6-arene)ruthenium bearing the carbene ligand 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) and 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) Ru(IMes)(Cl)2(η6-arene), Ru(IPr)(Cl)2(η6-arene), and [RuCCCPh2(IMes)(Cl)(η6-arene)]PF6 were prepared and found to be efficient catalyst precursors for ring closing olefin metathesis.

From olefin cyclopropanation to olefin metathesis through catalyst engineering: recent applications of olefin metathesis to fine organic synthesis and to polymer chemistry

An overview of the recent synthetic breakthroughs brought about by the discovery of new, functional group tolerant late transition metal (Rh and Ru)-based catalysts is proposed. Whereas dirhodium(II)-based complexes promote only carbene transfer reactions to olefins (i.e. olefin cyclopropanation), a few ruthenium-based catalysts can be engineered and fine tuned so as to mediate either carbene-transfer reactions or olefin metathesis. The different outcome of the reactions can be rationalized by the capability of the metal center to coordinate or not both the carbene and the olefin. This quite simple-minded approach indicates that several available coordination sites at the metal center favors metathesis reactions to the prejudice of olefin cyclopropanation. Examples of recent applications in ring opening metathesis polymerizations and copolymerizations include the formation of postpolymers of polydienes, of carbohydrate-substituted polymers and of telechelic oligomers. Application of the same ruthenium-based catalysts in ring-closing metathesis is illustrated by the formation of crown ether analogs, of unsaturated peptides and amino acids, of β-lactams, and of different bicyclic systems.

Asymmetric Ring-Closing Metathesis Catalyzed by Chiral Molybdenum Alkylidene Complexes.

Kinetic resolution was observed in ring-closing metathesis of racemic dienes catalyzed by the newly developed chiral molybdenum alkylidene complexes (R,R)-Mo(CHCMe(2)Ph)(NAr)(TBEC) 1 (Ar = 2,6-i-Pr(2)C(6)H(3), TBEC = 2',2',2",2"-tetrakis(trifluoromethyl)-1,2-bis(2'-hydroxyethyl)cyclopentane) and (R,R)-Mo(CHCMe(2)Ph)(NAr)(TBEH) 2 (Ar = 2,6-i-Pr(2)C(6)H(3), TBEH = 2',2',2",2"-tetrakis(trifluoromethyl)-1,2-bis(2'-hydroxyethyl)cyclohexane). In the case of a prochiral symmetric triene substrate, optically active cyclized product was formed by catalytic ring-closing metathesis with 1, which opens the possibility of a new version of two-directional synthesis. Although the observed enantiomeric excesses were modest to low, this data demonstrates the feasibility of asymmetric induction by chiral alkylidene catalysts in ring-closing metathesis.