[(NHC)(NHCewg)RuCl2(CHPh)] Complexes with Modified NHCewg Ligands for Efficient Ring‐Closing Metathesis Leading to Tetrasubstituted Olefins

Imidazolium salts (NHC_ewg ? HCl) with electronically variable substituents in the 4,5‐position (H,H or Cl,Cl or H,NO₂ or CN,CN) and sterically variable substituents in the 1,3‐position (Me,Me or Et,Et or iPr,iPr or Me,iPr) were synthesized and converted into the respective [AgI(NHC)_ewg] complexes. The reactions of [(NHC)RuCl₂(CHPh)(py)₂] with the [AgI(NHC_ewg)] complexes provide the respective [(NHC)(NHC_ewg)RuCl₂(CHPh)] complexes in excellent yields. The catalytic activity of such complexes in ring‐closing metathesis (RCM) reactions leading to tetrasubstituted olefins was studied. To obtain quantitative substrate conversion, catalyst loadings of 0.2–0.5 mol % at 80 °C in toluene are sufficient. The complex with the best catalytic activity in such RCM reactions and the fastest initiation rate has an NHC_ewg group with 1,3‐Me,iPr and 4,5‐Cl,Cl substituents and can be synthesized in 95 % isolated yield from the ruthenium precursor. To learn which one of the two NHC ligands acts as the leaving group in olefin metathesis reactions two complexes, [(FL‐NHC)(NHC_ewg)RuCl₂(CHPh)] and [(FL‐NHC_ewg)(NHC)RuCl₂(CHPh)], with a dansyl fluorophore (FL)‐tagged electron‐rich NHC ligand (FL‐NHC) and an electron‐deficient NHC ligand (FL‐NHC_ewg) were prepared. The fluorescence of the dansyl fluorophore is quenched as long as it is in close vicinity to ruthenium, but increases strongly upon dissociation of the respective fluorophore‐tagged ligand. In this manner, it was shown for ring‐opening metathesis ploymerization (ROMP) reactions at room temperature that the NHC_ewg ligand normally acts as the leaving group, whereas the other NHC ligand remains ligated to ruthenium.     

Total synthesis of the bacterial RNA polymerase inhibitor ripostatin b

A modular and highly stereoselective synthesis of the title compound was developed. Key steps in the assembly of the carbon framework of ripostatin?B (1; see scheme) were a stereoselective Paterson aldol reaction and a high-yielding ring-closing metathesis mediated by Grubbs first generation catalyst. The C15 hydroxy group was established through Tishchenko-Evans reduction in excellent yield and selectivity.     

A Retrospective on the Design and Synthesis of Novel Molecules through a Strategic Consideration of Metathesis and Suzuki–Miyaura Cross‐Coupling

Synergy in synthesis : Strategic consideration of metathesis and Suzuki–Miyaura (SM) cross‐coupling for C? C bond‐formation processes has opened up new and “green” synthetic routes to various complex targets. The use of this synergistic combination for the synthesis of supramolecular ligands, polyaromatic compounds, and complex natural products is covered in this Focus Review.

     

The Total Synthesis of (−)‐Nitidasin

Nitidasin is a pentacyclic sesterterpenoid with a rare 5‐8‐6‐5 carbon skeleton that was isolated from the Peruvian folk medicine “Hercampuri”. It belongs to a small class of sesterterpenoids that feature an isopropyl trans‐hydrindane moiety fused to a variety of other ring systems. As a first installment of our general approach toward these natural products, we report the total synthesis of the title compound. Our stereoselective, convergent route involves the addition of a complex alkenyl lithium compound to a trans‐hydrindanone, followed by chemoselective epoxidation, ring‐closing olefin metathesis, and redox adjustment.     

Thermal analysis of ring‐opening metathesis polymerized healing agents

Dicyclopentadiene (DCPD) and 5‐ethylidene‐2‐norbornene (ENB) and their mixtures were analyzed after ring‐opening metathesis polymerization (ROMP) in the presence of Grubbs catalyst as potential candidate healing agents for self‐healing composite materials using two complementary methods, rotational dynamic mechanical analysis (DMA) and differential scanning calorimetry (DSC). Following isothermal DMA measurements at room temperature (RT = 25 °C) for 120 min, two consecutive dynamic temperature scan experiments were performed for each system. In the first dynamic temperature scans, there was an initial downward peak slightly above RT in the storage modulus versus temperature curve for samples with relatively slower reaction rates (i.e., DCPD and DCPD‐rich mixtures or low catalyst loadings) due to a combination of the glass transition followed by further residual reaction. However, no or negligible downward peaks were observed for the highly reactive ENB and ENB‐rich samples even at much lower catalyst loadings. Implications of the substantial decrease in storage modulus just above RT for the slowly reacting systems are discussed for healing of damage in composite materials at elevated temperatures. The maximum glass transition temperatures (T_g∞) from DMA of the fully cured samples were determined to be approximately 160 °C for DCPD and 120 °C for ENB, decreasing linearly with increased ENB in the blends. The glass transitions and further residual reactions above the glass transitions were confirmed by DSC. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 1771–1780, 2007     

An [(NHC)(NHCEWG)RuCl2(CHPh)] Complex for the Efficient Formation of Sterically Hindered Olefins by Ring‐Closing Metathesis

NHC with EWGs for RCM : Ruthenium complexes with two N‐heterocyclic carbenes (NHCs), one of them substituted with electron‐withdrawing groups (EWGs), are highly efficient (pre)catalysts for the synthesis of tetrasubstituted olefins and trisubstituted olefins by ring‐closing metathesis reactions (RCM, see scheme).

     

Sequential Electrografting and Ring‐Opening Metathesis Polymerization: a Strategy for the Tailoring of Conductive Surfaces

Summary: An electrografting technique has been combined with ring‐opening metathesis polymerization (ROMP). Poly(allyl methacrylate) chains have been chemisorbed onto steel and carbon plates under an appropriate cathodic potential in N,N‐dimethylformamide. The allyl moieties have been converted into Ru catalysts active in ROMP of norbornene and its derivatives. Initiation of ROMP from the surface is an efficient strategy to prepare strongly adhering coatings of tunable thickness and hydrophilic/hydrophobic balance, depending on the norbornene derivative polymerized at the surface.

The hydrophobicity of the polymer coating may be controlled by hydrolysis of the polynorbornene derivative.     

The pivotal role of symmetry in the ruthenium-catalyzed ring-closing metathesis of olefins

The synthesis of Ru-based precatalysts with N-heterocyclic carbene (NHC) ligands bearing syn- and anti-methyl groups on the NHC backbone and aryl N-substituents with differing steric bulk was carried out. The catalytic behavior of the monophospine Ru precatalysts (7a, 7b, 8a, and 8b) was compared to the corresponding family of phosphine-free catalysts (9a, 9b, 10a and 10b) in the ring-closing metathesis (RCM) of olefins. These catalysts showed high efficiency in RCM reactions and the syn-isomers 7a and 9a, in particular, proved to be among the most active catalysts in the formation of tetrasubstituted olefins through RCM. DFT studies on the entire RCM catalytic cycle of hindered olefins were performed to rationalize the different behaviors of catalysts with syn- and anti-methyl groups on the NHC backbone. Theoretical results not only disclosed how NHC symmetry influences the overall activity of the catalyst, but also gave relevant and more general indications on the crucial steps of the RCM of olefins.     

Recent developments in olefin cross-metathesis

Among the many types of transition-metal-catalyzed C-C bond-forming reactions, olefin metathesis has come to the fore in recent years owing to the wide range of transformations that are possible with commercially available and easily handled catalysts. Consequently, olefin metathesis is now widely considered as one of the most powerful synthetic tools in organic chemistry. Until recently the intermolecular variant of this reaction, cross-metathesis, had been neglected despite its potential. With the evolution of new catalysts, the selectivity, efficiency, and functional-group compatibility of this reaction have improved to a level that was unimaginable just a few years ago. These advances, together with a better understanding of the mechanism and catalyst-substrate interactions, have brought us to a stage where more and more researchers are employing cross-metathesis reactions in multistep procedures and in the synthesis of natural products. The recent inclusion of alkynes and hindered bicyclic olefins as viable substrates for bimolecular metathesis coupling, the discovery of enantioselective cross-metathesis and cross-metathesis in water, and the successful marriage of metathesis and solid-phase organic synthesis has further widened the scope of this versatile reaction.     

关环复分解反应(RCM)及其催化剂研究进展

综述了近年来关环复分解 (RCM )反应及其催化剂的研究进展 ,对RCM反应发展以来被广泛应用的催化剂 ,如Schrock催化剂和Grubbs催化剂等进行了归纳和总结 ,讨论了RCM反应在全合成中的应用     

Ring-closing metathesis of sulfoximine-substituted N-tethered trienes: modular asymmetric synthesis of medium-ring nitrogen heterocycles

A synthesis of sulfoximine-substituted medium-ring nitrogen heterocycles (MRNHs) having a high degree of substitution has been developed. Its key steps are the modular asymmetric synthesis of sulfoximine-substituted N-tethered trienes and their Ru-catalyzed ring-closing metathesis (RCM) reaction. The highly substituted N-tethered trienes were obtained enantio- and diastereopure through 1) the diastereoselective aminoalkylation of sulfoximine-substituted allyltitanium complexes with N-tert-butylsulfonyliminoester, 2) N-allylation of homoallylic N-sulfonyl amines, 3) allylation, hydroxylalkylation, and formylation of α-lithioalkenylsulfoximines, and 4) allylation of α-formylalkenylsulfoximines. The Ru-catalyzed RCM reaction of the sulfoximine-substituted 1,7,10- and 1,7,12-trienes stereoselectively afforded the corresponding nine-, ten-, and eleven-membered MRNHs in good yields. An interesting difference in reactivity was noted in the case of a sulfoximine-substituted 1,7,10-triene and its corresponding 1,10-diene. While the triene readily underwent a RCM reaction, the diene reacted only in the presence of Ti(OiPr)(4) under formation of the corresponding MRNH. The feasibility of a removal of the sulfoximine auxiliary and the N-sulfonyl protecting group from the MRNHs were demonstrated through reduction and cleavage, respectively, of a nine-membered heterocycle, both of which proceeded readily and gave the corresponding cyclic alkene and amine, respectively.     

Novel Photoresponsive Linear,Graft, and Comb‐Like Copolymers with Azobenzene Chromophores in the Main‐Chain and/or Side‐Chain: Facile One‐Pot Synthesis and Photoresponse Properties

Novel photoresponsive linear, graft, and comb‐like copolymers with azobenzene chromophores in the main‐chain and/or side‐chain are prepared via a sequential ring‐opening metathesis polymerization (ROMP) and head‐to‐tail acyclic diene metathesis (ADMET) polymerization in a one‐pot procedure using Grubbs ruthenium‐based catalysts. The diluted solutions of these as‐prepared copolymers containing azobenzene chromophores exhibit photochemical trans–cis isomerization under the irradiation of UV light, followed by their cis–trans back‐isomerization in visible light. The rates of photoisomerization are found to be slower than those of back‐isomerization, and the rate for the comb‐like copolymer is found to be from 3 to 7 times slower than that obtained for the linear or graft copolymer. This is ascribed to the differences in structure of the copolymers and the specific location of azobenzene chromophores in the copolymer, which favor a side‐chain graft structure.

     

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.     

Total Synthesis of the Isodon Diterpene Sculponeatin N

The total synthesis of sculponeatin N, a bioactive polycyclic diterpene isolated from Isodon sculponeatus, is reported. Key features of the synthesis include diastereoselective Nazarov and ring‐closing metathesis reactions, and a highly efficient formation of the bicyclo[3.2.1]octane ring system by a reductive radical cyclization.     

Alpha,alpha-disubstituted glycines bearing a large hydrocarbon ring: peptide self-assembly through hydrophobic recognition

A method was developed for synthesizing alpha,alpha-disubstituted glycine residues bearing a large (more than 15-membered) hydrophobic ring. The ring-closing metathesis reactions of the dialkenylated malonate precursors proceed efficiently, particularly when long methylene chains tether both terminal olefin groups. Surprisingly, the amino groups of these alpha,alpha-disubstituted glycines are inert to conventional protective reactions (e.g., N-tert-butoxycarbonyl (Boc) protection: Boc(2)O/4-dimethylaminopyridine (DMAP)/CH(2)Cl(2); N-benzyloxycarbonyl (Z) protection: Z-Cl/DMAP/CH(2)Cl(2)). Curtius rearrangement of the carboxylic acid functionality of the malonate derivative after ring-closing metathesis leads to formation of an amine functionality and can be catalyzed by diphenylphosphoryl azide. However, only the intermediate isocyanates can be isolated, even in the presence of alcohols such as benzyl alcohol. The isocyanates obtained by Curtius rearrangement in an aprotic solvent (benzene) were isolated in high yields and treated with 9-fluorenylmethanol in a high-boiling-point solvent (toluene) under reflux to give the N-9-fluorenylmethoxycarbonyl (Fmoc)-protected aminomalonate derivatives in high yield. These hydrophobic amino acids can be incorporated into a peptide by Fmoc solid-phase peptide synthesis and the acid fluoride activation method. The stability of the monomeric alpha-helical structure of a 17-amino-acid peptide was enhanced by replacement of two alanine residues with two hydrophobic amino acid residues bearing a cyclic 18-membered ring. The results of sedimentation equilibrium studies suggested that the peptide assembles into hexamers in the presence of 100 mM NaCl.     

Oxidation‐Triggered Ring‐Opening Metathesis Polymerization

Eight new N‐Hoveyda‐type complexes were synthesized in yields of 67–92 % through reaction of [RuCl₂(NHC)(Ind)(py)] (NHC=1,3‐bis(2,4,6‐trimethylphenylimidazolin)‐2‐ylidene (SIMes) or 1,3‐bis(2,6‐diisopropylphenylimidazolin)‐2‐ylidene (SIPr), Ind=3‐phenylindenylid‐1‐ene, py=pyridine) with various 1‐ or 1,2‐substituted ferrocene compounds with vinyl and amine or imine substituents. The redox potentials of the respective complexes were determined; in all complexes an iron‐centered oxidation reaction occurs at potentials close to E=+0.5 V. The crystal structures of the reduced and of the respective oxidized Hoveyda‐type complexes were determined and show that the oxidation of the ferrocene unit has little effect on the ruthenium environment. Two of the eight new complexes were found to be switchable catalysts, in that the reduced form is inactive in the ring‐opening metathesis polymerization of cis‐cyclooctene (COE), whereas the oxidized complexes produce polyCOE. The other complexes are not switchable catalysts and are either inactive or active in both reduced and oxidized states.     

Cationic versus neutral Ru(II)--N-heterocyclic carbene complexes as latent precatalysts for the UV-induced ring-opening metathesis polymerization

A series of cationic and neutral Ru^II complexes of the general formula [Ru(L)(X) (tBuCN)₄]⁺X^? and [Ru(L)(X)₂(tBuCN)₃)], that is, [Ru(CF₃SO₃){NCC(CH₃)₃}₄(IMesH₂)]⁺[CF₃SO₃]^? ( 1 ), [Ru(CF₃SO₃){NCC(CH₃)₃}₄(IMes)]⁺[CF₃SO₃]^? ( 2 ), [RuCl{NCC(CH₃)₃}₄(IMes)]⁺Cl^? ( 3 ), [RuCl{NCC(CH₃)₃}₄(IMesH₂)⁺Cl^?]/[RuCl₂{NCC(CH₃)₃}₃(IMesH₂)] ( 4 ), and [Ru(NCO)₂{NCC(CH₃)₃}₃(IMesH₂)] ( 5 ) (IMes=1,3‐dimesitylimidazol‐2‐ylidene, IMesH₂=1,3‐dimesityl‐imidazolin‐2‐ylidene) have been synthesized and used as UV‐triggered precatalysts for the ring‐opening metathesis polymerization (ROMP) of different norborn‐2‐ene‐ and cis‐cyclooctene‐based monomers. The absorption maxima of complexes 1 – 5 were in the range of 245–255 nm and thus perfectly fit the emission band of the 254 nm UV source that was used for activation. Only the cationic Ru^II‐complexes based on ligands capable of forming μ²‐complexes such as 1 and 2 were found to be truly photolatent in ROMP. In contrast, complexes 3 – 5 could be activated by UV light; however, they also showed a low but significant ROMP activity in the absence of UV light. As evidenced by ¹H and ¹³C NMR spectroscopy, the structure of the polymers obtained with either 1 or 2 are similar to those found in the corresponding polymers prepared by the action of [Ru(CF₃SO₃)₂(IMesH₂)(CH‐2‐(2‐PrO)‐C₆H₄)], which strongly suggest the formation of Ru‐based Grubbs‐type initiators in the course of the UV‐based activation process. Precatalysts that have the IMesH₂ ligand showed significantly enhanced reactivity as compared with those based on the IMes ligand, which is in accordance with reports on the superior reactivity of IMesH₂‐based Grubbs‐type catalysts compared with IMes‐based systems.     

A Precision Ethylene‐Styrene Copolymer with High Styrene Content from Ring‐Opening Metathesis Polymerization of 4‐Phenylcyclopentene

Ring‐opening metathesis polymerization of 4‐phenylcyclopentene is investigated for the first time under various conditions. Thermodynamic analysis reveals a polymerization enthalpy and entropy sufficient for high molar mass and conversions at lower temperatures. In one example, neat polymerization using Hoveyda–Grubbs second generation catalyst at −15 °C yields 81% conversion to poly(4‐phenylcyclopentene) (P4PCP) with a number average molar mass of 151 kg mol⁻¹ and dispersity of 1.77. Quantitative homogeneous hydrogenation of P4PCP results in a precision ethylene‐styrene copolymer (H₂‐P4PCP) with a phenyl branch at every fifth carbon along the backbone. This equates to a perfectly alternating trimethylene‐styrene sequence with 71.2% w/w styrene content that is inaccessible through molecular catalyst copolymerization strategies. Differential scanning calorimetry confirms P4PCP and H₂‐P4PCP are amorphous materials with similar glass transition temperatures (T_g) of 17 ± 2 °C. Both materials present well‐defined styrenic analogs for application in specialty materials or composites where lower softening temperatures may be desired.

     

Development of hydrogenated ring‐opening metathesis polymers

New hydrogenated ring‐opening metathesis polymers with excellent thermal and optical properties were developed. These polymers were prepared by the ring‐opening metathesis polymerization of ester‐substituted tetracyclododecene monomers followed by the hydrogenation of the main‐chain double bond. The degree of hydrogenation was an important factor for the thermal stability of the polymers, and as complete hydrogenation as possible was necessary to obtain a thermally stable polymer. The completely hydrogenated ring‐opening polymer derived from 8‐methyl‐8‐methoxycarbonyl‐substituted monomer has a glass‐transition temperature of 171 °C and a 5% weight‐loss temperature of 446 °C. This polymer has excellent thermal and optical properties because of its bulky and unsymmetrical polycyclic structure in the main chain and is an alternative to glass or other transparent polymers such as poly(methyl methacrylate) and polycarbonate resin. This polymer has also been used in a wide variety of applications, such as optical lenses, optical disks, optical films, and optical fiber. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4661–4668, 2000     

One‐Step Ring Opening Metathesis Block‐Like Copolymers and their Compositional Analysis by a Novel Retardation Technique

Using a one‐step synthetic route for block copolymers avoids the repeated addition of monomers to the polymerization mixture, which can easily lead to contamination and, therefore, to the unwanted termination of chain growth. For this purpose, monomers ( M1 – M5 ) with different steric hindrances and different propagation rates are explored. Copolymerization of M1 (propagating rapidly) with M2 (propagating slowly), M1 with M3 (propagating extremely slowly) and M4 (propagating rapidly) with M5 (propagating slowly) yielded diblock‐like copolymers using Grubbs’ first ( G1 ) or third generation catalyst ( G3 ). The monomer consumption was followed by ¹H NMR spectroscopy, which revealed vastly different reactivity ratios for M1 and M2 . In the case of M1 and M3 , we observed the highest difference in reactivity ratios (r₁=324 and r₂=0.003) ever reported for a copolymerization method. A triblock‐like copolymer was also synthesized using G3 by first allowing the consumption of the mixture of M1 and M2 and then adding M1 again. In addition, in order to measure the fast reaction rates of the G3 catalyst with M1 , we report a novel retardation technique based on an unusual reversible G3 Fischer‐carbene to G3 benzylidene/alkylidene transformation.