Metathesis and Polymerization

Abstract

This article reviews olefin metathesis, its history, use of heterogeneous and well-defined molecular catalysts, mechanism related to organometallic chemistry and application of the reactions. Group VI and VIII transition metal catalysts are the most common in the olefin metathesis, although several other transition metal compounds also catalyze the reaction. The olefin metathesis is used in the ring-opening polymerization of the strained cyclic olefins, while acyclic unsaturated molecules can also be adopted as the monomer of the polymerization, and the substrate for the ring-closing metathesis or cross metathesis reactions. Application of the olefin metathesis is extended to synthesis of the new functionalized polymers, organometallic compounds, organic compounds from marine animals, and interlocked molecular systems.

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7.1 Introduction

Olefin metathesis reaction involves mutual exchange of the carbon-carbon double bonds catalyzed by transition metal complexes, as shown in Scheme 7.1. It causes cleavage of the two C=C double bonds and formation of new C=C double bonds under mild conditions.

Scheme 7.1

Olefin metathesis

Historical background of the olefin metathesis is quite exciting to the scientists of organometallic, macromolecular, organic, and catalytic chemistry. The olefin metathesis was discovered during the study of olefin polymerization using Ziegler-Natta type catalysts [1]. Eleuterio in DuPont Co. conducted the study on the Mo-based catalysts for propylene polymerization, and found the formation of the polymer containing ethylene units in the polymer chain. It was ascribed to the metathesis of propylene, giving ethylene and 2-butene, during the polymerization. Another productive olefin metathesis reaction was found also during the study of polymer synthesis. Cyclobutene undergoes vinyl polymerization in the presence of VCl₄–AlEt₃ catalyst, similar to many other cyclic olefins with ring strain [2, 3]. The product contains four-membered cyclic group in every repeating unit. Use of TiCl₄–AlEt₃ catalyst, however, afforded the polymer with the C=C double bonds and without a ring structure, as shown in Scheme 7.2 [4]. The polymer attracted attention because of its cis-rich polybutadiene structure and the rubbery properties.

Scheme 7.2

Polymerization of cyclobutene

Calderon summarized these apparently different reactions promoted by various transition metal catalysts and concluded that all the reactions proceed by exchange of the alkylidene groups (=CRR’) rather than transalkylation [5]. He also named them as olefin metathesis, although the other ones, such as olefin disproportionation, had been proposed by other research groups.

The mechanism of this novel reactions had been under discussion by several research groups, and the final mechanism was proposed by Hérisson and Chauvin in 1971, which involves organometallic intermediates [6]. Their proposed mechanism is summarized in Scheme 7.3. The intermediates having a carbene ligand are generated upon mixing the transition metal compounds and the alkylaluminum. Addition of a C=C double bond to the metal-carbene bond yields the metallacyclobutane having a four-membered ring, and elimination of the olefin product regenerates the new carbene-transition metal complexes. Structures of the products of the olefin metathesis and ring-opening metathesis polymerization are consistent with those based on the mechanism. The apparently reversible mechanism explains results of the olefin metathesis reactions. The multicomponent catalysts composed of transition metal salts, basically of Mo and W, and alkylaluminum, were employed in a number of the reactions.

Scheme 7.3

Mechanism of olefin metathesis

Study of the transition metal complexes with carbenoid or metallacyclobutane structures were directed toward the clarification of the reaction mechanism. Although the transition metal complexes with carbene ligands were isolated, many of them prepared in the initial period did not promote the olefin metathesis reactions, efficiently. Casey prepared the tungsten complex with a diphenylcarbene ligand, W(=CPh₂)(CO)₅, starting from a “Fischer type” complex, W(=CPh(OMe))(CO)₅, and found that the reaction of olefin with the complex yielded the products of the stoichiometric metathesis reaction [7, 8]. Katz employed the complex as the catalyst of metathesis of isotope-labelled 1-olefins and obtained all the products expected from the olefin metathesis reaction [9].

The olefin metathesis has advantages in a variety of the catalysts, which enabled choice of the best catalyst for each reaction, high atomic economy, and mild reaction conditions. Ring-opening polymerization of the olefins equipped with four- and five-membered rings and with strained multicyclic ring systems proceeds smoothly to yield the corresponding polymers owing to higher stability of the products. Strained structures of the monomers served to the smooth reaction, which is accompanied by release of the ring strain. Although the olefin metathesis reaction occurs reversibly, discovery of the highly active catalyst during these decades enabled the selective reactions of the less strained or unstrained substrates. Ring-closing metathesis of terminal dienes and cross-metathesis of two terminal olefins convert the substrates to the cyclic or acyclic products easily when the reaction system is designed to release gaseous ethylene product from the reaction mixture. Selectivity of the reactions, including E/Z selectivity and enantioselectivity of the products, has been improved by design of the new molecular catalysts.

The following sections describe the representative catalysts and reactions and recent application of the olefin metathesis.

7.2 Catalysts

7.2.1 Multicomponent Catalysts

The initial olefin metathesis catalysts were mostly the heterogeneous ones similar to the Ziegler-Natta type catalysts, as mentioned in the previous section. Norbornene, having a bicyclic structure, undergoes ring-opening metathesis polymerization in the presence of the two component catalysts, transition metal salts and alkylaluminum. TiCl₄–LiAlH₄ catalyst also promotes the reaction of norbornene derivatives [10]. Chlorides of many transition metals, such as Ti, Zr, V, Mo, and W, catalyze the ring-opening polymerization of cyclopentene and cycloheptene in the presence of AlEt₂X (X = Et, Cl) (Scheme 7.4i, ii) [11].

Scheme 7.4

Ring-opening metathesis polymerization by Mo and W catalysts

Norbornenes with fluorinated substituents undergo the smooth reaction catalyzed by a WCl₆–AlEt₂Cl mixture to produce the fluorinated polymers (Scheme 7.4iii, iv) [12, 13]. Feast designed the multicyclic monomers with ring strain and conducted the ring-opening polymerization to obtain the polymers having a fluorinated multicyclic group in every structural unit (Scheme 7.4v) [14, 15]. Each repeating unit undergoes thermally induced retro-Diels-Alder reactions to produce the polyacetylene accompanied by elimination of the fluorinated aromatic compound. Since the precursor polymer of polyacetylene are soluble, their molecular weight and the molecular weight of the resulted polyacetylene can be estimated. Physical properties of the polyacetylene obtained by this method were investigated by using spectroscopies and X-ray diffraction, and compared with that obtained from acetylene using Shirakawa’s method [16, 17].

The reactions using the heterogenous catalysts still have importance in industrial process. The reactions and catalysis in the industry are surveyed in the recent review articles [18, 19]. Two-component catalysts have been employed in the polymer synthesis in an industrial scale. In addition to the cocatalysts, organotin compounds or transition metal salts are also added as the third component of the catalysts. It is used in the ring-opening polymerization of norbornene and other cyclic olefins to form the tough and flexible polymer material in a molded shape. The heterogeneous catalysts for olefin polymerization are obtained by using the metal oxides as the support. Re(VII) oxide supported on alumina and Mo(VI) oxide supported on silica are the common heterogeneous catalysts for olefin metathesis.

7.2.2 Homogeneous Catalysts

The heterogeneous catalysts for olefin metathesis, composed of the transition metal salts and alkylating reagents, are highly active. Although the initial molecular catalysts showed much lower activity than the heterogeneous ones, the new molecular catalysts, alkylidene complexes of Mo and Ru, in particular, improved their performance and enabled the reactions which had not been realized by the conventional heterogeneous catalysts.

Several heterogeneous catalysts still show higher activity than those using most molecular catalysts. The ring-opening metathesis polymerization of cyclic olefins catalyzed by molecular transition metal complexes, however, has advantage in regulation of molecular weights of the products. Stereoselective polymerization of norbornene derivatives was also achieved. Introduction of chiral substituents on the ligand of the complexes induced chirality to the products, polymers and organic compounds.

A number of books and reviews on the olefin metathesis using molecular catalysts are available [20–29]. In this section, representative catalysts and their reactions are briefly mentioned, and recent application of the olefin metathesis is summarized in the next section.

7.2.2.1 Mo and W Catalysts

The proposal of the mechanism for the olefin metathesis prompted the studies on the synthesis of alkylidene (substituted carbene)-transition metal complexes as well as their reactions towards olefins. Schrock succeeded in synthesis of Ta and Nb complexes with neopentilydene ligands from α-hydrogen elimination reaction of the neopentyl complexes [30]. Tungsten complex with a neopentilydiene ligand, WCl₂(=O)(=CHCMe₃)(PEt₃)₂, was obtained by transmetalation of the alkylidene ligand of the Ta complex and catalyzed metathesis of inner olefins in the presence of AlCl₃ cocatalyst.

The well-defined molecular catalyst, W(OR)₂(=CHCMe₃)(=N(2,6-(iPr)₂C₆H₃)) (R = tBu, C(CF₃)₂Me), was obtained by the procedure shown in Scheme 7.5 [31, 32]. These complexes exhibit high catalytic activity for the ring-opening metathesis polymerization, the ring-closing metathesis, and cross-metathesis reactions without using a cocatalyst. Bulky arylimide and alkoxide ligands are introduced to the complex. Although the complex contains tetra-coordinate metal center, the sterically bulky ligands stabilize the metal center and prevent the molecule from undesired dimerization. The alkoxide ligands with electron-withdrawing CF₃ groups lower the LUMO level of the complex and make coordination of the olefin substrate easy.

Scheme 7.5

Synthesis of W-alkylidene complex

The Mo analogues are obtained in a similar manner, and exhibit higher catalytic activity than the W catalyst. One of the striking features of the Mo catalyst is living ring-opening polymerization of the cyclic olefins, as shown in Scheme 7.6 [33–35]. The reaction is initiated by addition of the C=C bond of norbornene to the Mo=C bond and cleavage of the resulted four-membered metallacycle. The yielded cyclopentylmethylidene-Mo compound undergoes repeated reactions with norbornene to cause polymer growth. Quenching of the growing polymer end with aromatic aldehydes results in the polymers having terminal CMe₂Ph group, derived from the initiator, and the aromatic end group (Scheme 7.6i). The terminal structure of the polymer indicates that the growing polymer end has the alkylidene =Mo bond, which undergoes Wittig-type coupling with the aldehydes. Molecular weight and polydispersity of the polymer are consistent with the living polymerization with quantitative efficiency of the Mo-containing initiator. Synthesis of AB type block copolymer from the two norbornene derivatives with different substituents was also noted (Scheme 7.6ii). Thus, the polymerization system has advantages in productivity, control of molecular weights, block copolymer formation, and functionalization of the terminal groups. High sensitivity of the catalyst to oxygen and water, however, makes purification of the substrates and the solvent, and handling the catalyst under air- and moisture-free conditions required.

Scheme 7.6

Ring-opening metathesis polymerization catalyzed by Mo-alkylidene complexes

The catalyst in Scheme 7.5 has a symmetrical structure owing to the almost linear M–O–C and M–O–N bonds. Thus, syn and anti structures around the alkylidene=Mo bond (Scheme 7.7) influence the stereochemistry of the reaction with the olefin substrates. Addition of exo,exo-disubstituted norbornene to the stable syn-alkylidene-Mo complex results in the linkage of cis-vinylene group between the five-membered rings (Scheme 7.7i).

Scheme 7.7

Stereoselective ring-opening metathesis polymerization of norbornene

The polymer structures are regulated strictly by using recent Mo catalysts. The exo,exo-norbornene derivatives are converted to the polymer having a cis,syndiotactic structure as shown in Scheme 7.8 [36–38]. Exo,end-norbornene monomer produces the polymer having trans,isotactic structures along the polymer chain.

Scheme 7.8

Cis- and trans-polymers of norbornene

7.2.2.2 Ru Catalysts

RuCl₃ was known to catalyze the ring-opening polymerization of norbornene in polar solvents such as BuOH, which was applied to the polymer synthesis in an industrial scale [18]. Ru(II)-phosphine complexes, such as RuCl₂(PPh₃)₃, catalyze metathesis of silyl ethenes [39–41]. Addition of organosilanes having an Si–H bond or reducting agents such as NaBH₄ to the reaction mixture is required to make the reaction smooth.

[Ru(H₂O)₆](Tos)₂ was found to catalyze the ring opening polymerization of the functionalized norbornene without addition of a cocatalyst [42]. The catalyst is easy to prepare and works efficiently even in aqueous media. The first well-defined molecular Ru catalysts that do not require cocatalyst were discovered in the line of this study; the Ru complex with a vinylmethylidene ligand (Scheme 7.9i) was obtained from the reaction of dimethylcyclopropene with RuCl₃ and the resulted complex catalyzes the olefin metathesis. Further studies led to discovery of the well-refined metathesis catalysts, RuCl₂(=CHPh)(PR₃)₂ (R = Ph, Cy) (Scheme 7.9ii) [43, 44]. Replacement of a phosphine of the above complexes with an NHC (N-heterocyclic carbene) ligand provides the molecular catalyst with a higher activity (Scheme 7.9iii) [45]. These two complexes are known as the first- and second-generation Grubbs catalysts, respectively. The benzylidene ligand of the complexes reacts with the olefin substrate at the initial stage of the reaction, while the alkylidene-Ru species formed by the olefin metathesis has a similar coordination structure and resumes the metathesis reaction. High activity of the NHC-containing catalyst is attributed to facile dissociation of the phosphine ligand at the trans position of the NHC, as shown in (iv) [46–48]. Highly electron-donating NHC ligand activates the Ru–P bond, but does not influence the Ru-olefin bond. Thus, olefin coordination to the Ru center is facilitated by the NHC ligand, which results in high catalytic activity for the reaction. The first-generation Grubbs catalyst, after the reaction, can be removed from the organic product by addition of P(CH₂OH)₃ to the reaction mixture and extraction of the Ru catalyst residue bonded with the water-soluble phosphine ligands [49].

Scheme 7.9

Ru catalysts for olefin metathesis (i–iii) and their activation process (iv)

The above Ru complexes catalyze ring-opening polymerization of not only norbornene derivatives but also less-strained cyclic olefins such as cyclooctene [50–52]. The product of the ring-opening polymerization of cyclooctene is the hydrocarbon polymer composed of the eight carbon repeating units having a C=C bond, while the reaction of cyclooctatetraene derivatives produces the substituted polyacetylenes. Grubbs designed the Ru catalyst with the NHC ligand whose nitrogen atom is connected to the coordinating carbene carbon through an oligomethylene spacer (Scheme 7.10). Ring-opening polymerization of cyclooctene catalyzed by the complex afforded the species having a ruthenacycle with a large ring structure [53–55]. The ring-opening polymerization was applied to the other monomers, and substituted norbornene is converted to the macrocyclic polymer with high molecular weight, and a single molecule of the polymer was analyzed by AFM technique [56].

Scheme 7.10

Synthesis of cyclic poly(cyclooctene)

This catalysis provides synthesis of the macrocyclic polymer with regulated molecular weights, which is of interest because of the expected physical properties of the cyclic polymer different from the corresponding linear polymers. Only a few reports have appeared on the macrocyclic polymer with regulated molecular weights until very recently [57–59].

The olefin metathesis reactions which are quite important in their application are ring-closing metathesis of terminal dienes. The catalysts are active for various substrates, and form the complexes from five-membered rings to macrocyclic compounds. The catalysts are not influenced by functional groups in the molecules of the starting compounds. 1,6-Hexadiene with COOEt groups, for example, undergoes smooth ring-closing metathesis reaction to produce the cyclopentene having the functional groups (Scheme 7.11). The reaction is closely related to the application of the olefin metathesis which is mentioned in Sect. 7.3.

Scheme 7.11

Ring-closing olefin metathesis

7.2.2.3 Molecular Catalysts Using Other Transition Metals

Rhenium is among the central metals used in the heterogeneous catalysts for the olefin metathesis reactions [60], similar to Mo, W, and Ru. Penta-coordinated alkylidene Re complexes with the bulky auxiliary arylimide ligand catalyze the reaction in the presence of Lewis-acid cocatalysts such as AlCl₃ and GaCl₃ [61]. A bulky alkylidyne ligand forms the tetrahedral complex (Scheme 7.12i) which is isoelectronic to the highly catalytically active imido(alkylidene)molybdenum complex (ii) [62–64]. The complex with two OC(CF₃)₂Me ligands catalyzes the metathesis of inner olefins.

Scheme 7.12

Ru- and Mo-alkylidene catalysts for olefin polymerization

The complex with alkyl, alkylidene, and alkylidyne ligands on the Re center also catalyzes metathesis of inner olefins, although the catalytic activity is not stable at high temperature or after a long reaction period [65]. Rhenium complex having an oxo (=O) ligand shows a moderate catalytic activity in the presence of GaBr₃ cocatalyst [66]. Fixation of the Re catalyst on the silica surface provided the olefin metathesis catalyst with high activity [67].

Although Ti is one of the first transition metals used as the catalyst in the presence of alkylaluminum cocatalysts, the activity of the isolated complex with a Ti=C bond was not high [68]. The adduct of AlMe₂Cl to the methylene-titanium complex, Tebbe reagent [69], was converted to titanacyclobutane upon the reaction with norbornene in the presence of pyridine or dimethylaminopyridine [70]. The resulted complex initiates the living ring-opening polymerization of norbornene derivatives without addition of a cocatalyst (Scheme 7.13). The polymer has regulated molecular weights having the titanocyclobutane end group. The rate-determining step resides in the cleavage reaction of the four-membered ring. Addition of aldehyde to the living polymer yields the polymer having the functionalized terminal group due to the addition of the C=O bond to the Ti=C bond [71, 72].

Scheme 7.13

Ring-opening metathesis polymerization via titanacyclobutane

Vanadium (V) complexes which catalyze the ring-opening metathesis polymerization were reported more recently than those using the Mo, W, Ru, and Ti catalysts. Dichlorovanadium complexes with arylimide and bulky aryloxide complexes (Scheme 7.14i, X = Cl) catalyzes ethylene polymerization in the presence of the cocatalyst [73]. The complex having 2,6-di(isopropyl)phenoxy ligand ((i), X = Cl, R = iPr) catalyzes the ring-opening metathesis polymerization of norbornene in the presence of AlMe₃ cocatalyst, while the catalyst with Et₂AlCl cocatalyst promotes ethylene polymerization [74].

Scheme 7.14

Vanadium catalysts for olefin metathesis

The dibenzyl complexes ((i) X = CH₂Ph, R = i-Pr) catalyze the ring-opening metathesis polymerization in the absence of a cocatalyst at room temperature. The dichloro complex having a bulky imine ligand ((ii), X = Cl) catalyzes the reaction in the presence of MeMgBr and PMe₃ [75]. Dibenzyl complex ((iii), X = CH₂Ph) is converted to an alkylidene complex ((iv), X = CH₂Ph) upon addition of PMe₃, and the produced complex catalyzes the ring-opening metathesis polymerization of norbornenes [76, 77]. The catalytic activity at room temperature is lower than Mo(CHCMe₂Ph)(N-(2,6-i-Pr)₂C₆H₃)(O-t-Bu)₂, but the vanadium complex shows increased activity even at high temperature (80 °C). Synthesis and properties of the complexes are summarized in a recent review article [78].

7.3 Application of Olefin Metathesis

This section includes development of the olefin metathesis reactions to synthesis of the new target molecules. The Mo and Ru complexes are commonly used as the molecular catalyst. Scheme 7.15 summarizes the catalyst used in this section. Most of the complexes do not require addition of cocatalysts.

Scheme 7.15

Highly reactive catalysts for olefin metathesis

7.3.1 Synthesis of the Polymers with New Structures and Functionality

Ring-opening polymerization of norbornene derivatives is utilized to synthesis of the polymer having unique molecular structures and conformations [79]. The monomer equipped with a pyrolidine pendant that is connected to the Zn-porphyrin undergoes polymerization in the presence of Ru catalysts A and B (Scheme 7.15). The zinc porphyrin groups in the structural units are aligned coherently along the polymer chain [80, 81]. Significant fluorescence quenching is observed, and is attributed to the effective π–π stacking of the porphyrin groups [80] (Scheme 7.16). The monomer with a chiral carbon in the spacer between the porphyrin and norbornene groups is converted to the polymer with a helical conformation [81].

Scheme 7.16

Porphyrin-containing poly(norbornene)

Bifunctional monomer in Scheme 7.17 has two norbornene terminal groups and undergoes the ring-opening polymerization of both groups in a parallel fashion. The obtained polymer has a ladder structure [82–85]. The cis isotactic structure of the norbornene polymer as well as the rigid spacer structure between the two norbornene groups of the monomer molecules enabled the efficient formation of the ladder polymer. The aligned ladder structure of the polymer and its helical structure can be observed directly by using STM image techniques.

Scheme 7.17

Synthesis and degradation of the ladder-type poly(norbornene)

The strained conformation of the polymer in Scheme 7.17 enhances the interaction of the ferrocenyl groups at close positions. Electrochemical oxidation of the ferrocenylene groups in the polymer to ferrocenium makes the polymer antiferromagnetic owing to the interaction of the neighboring Fe centers. The ladder-type polymer having ester groups between the two polymer strands is converted to the polymer composed of a single chain by hydrolysis of the ester groups. The polynorbornene template formed by the ring-opening polymerization is used in the polycondensation of alkynyl(halo)arene with a similar molecular weights to the starting polymer [86].

7.3.2 Synthesis and Reactions of the Ligand of Transition Metal Complexes

Most of the transition metal complexes are composed of the metal center which is reactive towards many chemical reagents and the chemically inert ligands. Thus, selective transformation of a ligand of the complexes is not common. Recent successful application of the olefin metathesis reaction to synthesis and modification of the organometallic complexes is mentioned below.

Metallocene derivatives whose two cyclopentadienyl ligands have a vinyl pendant undergo the ring-closing metathesis reaction in the presence of the Ru and Mo catalysts. The ferrocene derivative, and zirconoccene dichloride derivative with the allylic substituents are converted to the metallocenophanes owing to the intramolecular olefin metathesis reactions ((i), (ii) in Scheme 7.18) [87]. Unsymmetrically substituted metallocenes have planar chirality depending on the position of the substituents on the cyclopentadienyl ligands. The ring-closing metathesis of the acyclic metallocene derivatives catalyzed by optically active Mo complexes induces kinetic resolution [88–90]. Ferrocene derivatives having an allyl group and two tert-butyl groups on the cyclopentadienyl ligand undergo the ring-closing metathesis reaction in the presence of the Mo catalyst having a chiral binaphtholato ligand (iii).

Scheme 7.18

Synthesis of metallocenophanes

The racemic mixture of the chiral ferrocene derivatives undergo the kinetic resolution during the ring-closing metathesis reaction, which forms the (R)-ferrocenophane product and leaves the starting material with (S)-configuration. The phosphaferrocene with two equivalent allylic groups in the phosphacyclopentadienyl ligand undergoes the enantiotopos differentiating ring-closing metathesis in the presence of the optically active Mo catalysts and produces one of the chiral ferrocenophanes selectively (iv) [91]. Arene-chromium complex ((v) in Scheme 7.18) also undergoes the ring-closing metathesis with kinetic resolution to form the optically active complex having the arene ligand with the phosphine-containing pendant [92]. The two vinyl groups of a cyclopentadienyl ligand of the ferrocene derivatives produce the ligand with new cyclic groups (vi) [93, 94].

Intermolecular olefin metathesis of the transition metal complexes having the ligand with the terminal alkenyl groups forms the dinuclear complexes having a vinylene linker. Further hydrogenation of the C=C double bond produces the complexes whose metal centers are connected by oligomethylene chains. The dimerization of dichlorotitanocene having the allyl substituent on a cyclopentadienyl ligand affords the dinuclear complex [95]. Use of Ru catalyst A (Scheme 7.15) causes formation of the complex having a cis-vinylene group, while the reaction catalyzed by B yields the complex with a trans vinylene group (Scheme 7.19i). Dimerization of ansa-zirconocene and cyclopentadienyl(fluorenyl)zirconium dichloride [95, 96] was also reported ((ii) and (iii)). These dinuclear complexes are employed as the catalyst for polymerization of ethylene and/or propylene in the presence of MAO catalyst.

Scheme 7.19

Dinuclear complexes of Ti and Zr

The cross-metathesis reaction, which converts the two terminal olefins into an internal olefin and ethylene, was studied by using the transition metal complexes as the catalyst (Scheme 7.20) [97]. The selective cross-metathesis of α-olefin with acrylic esters was achieved by using the Ru catalyst with an NHC ligand (catalyst B in Scheme 7.15). The reaction is used in the coupling of the two metal complexes having alkenyl pendant groups, and it gave the Zr–Ni complex having vinylene acrylic ester linkage ((iv) in Scheme 7.19) [98]. The complex catalyzes ethylene polymerization to produce the polymer having long (>C10) branches along the polymer chain. The reaction probably involves oligomerization of ethylene on the Ni site and copolymerization of the resulted 1-olefin and ethylene on the Zr center.

Scheme 7.20

Cross-metathesis reaction

Stable rhenocene complex with 7-octenyl substituent on the cyclopentadienyl ligand undergoes the dimerization in the presence of the Ru catalyst, and produces the dinuclear complexes with a long polymethylene spacer (Scheme 7.21i) [99]. The complex with a ligand having two vinyl groups undergoes the ring-closing metathesis reaction. The S– and P– ligand with two ω-alkenyl substituents are cyclized via the intramolecular ring-closing olefin metathesis reactions. Scheme 7.21ii, iii show the formation of 2,5-dihydrothiophene ligand and the phosphine ligand having a fifteen-membered ring.

Scheme 7.21

Inter- and intra-molecular olefin metathesis of Re complexes

The Pt(II) complexes having two (7-octenyl)diphenylphosphine ligands at the cis positions in the square-planar structure are converted to the complex having a diphosphine ligand with a long spacer, but the dinuclear product is also formed by the intermolecular olefin metathesis (Scheme 7.22i) [100]. The ratio of the mononuclear and dinuclear products is 9:91, and they are equilibrated via reversible ring-opening and closing metathesis reactions. The square-planar Rh(I) complex having two alkenyl phosphine ligands at the trans positions causes the intramolecular reaction selectively to afford the macrocyclic complex (Scheme 7.22ii).

Scheme 7.22

Olefin metathesis of vinyl groups of the ligand

The Fe(0) complex having two tris(7-octenyl)phosphine ligands at the apical positions of the trigonal bipyramidal structure undergoes triple intramolecular olefin metathesis of the vinyl groups to form the complex having three polymethylene spacers between the two phosphorus atoms ((i) in Scheme 7.23) [101]. X-ray crystallographic results demonstrated that the three CO ligands and three oligomethylene chain are orientated to a staggered directions. Oxidation of the complex with NOBF₄ produced the cationic complex with an NO ligand. The Pt analogue was also reported, and the complex is demetalated by KCN to leave the multicyclic bisphosphine (ii) [102].

Scheme 7.23

Molecular gyroscope

1,4-Bissilylphenylene derivative having three 7-octenyl substituents on an Si atom is converted to the tricyclic compound with three oligomethylene spacers between the two Si atoms (iii) [103]. The central phenylene plane is rotated on the ²H NMR time scale even in the crystalline state within the cage made of the three oligomethylene chains. The crystalline phase transition occurs around 310 K, which is attributed to change of the velocity of the rotation of the phenylene group. Accompanying change of the birefringence of the crystals is observed [104, 105].

7.3.3 Synthesis of Natural Products

Many natural products contain a macrocylic ring system in the molecule, and its chemical synthesis requires efficient ring-forming reactions. The reaction should be chemo-, regio-, and stereo-selective and should be conducted under the conditions which are not disturbed by the functional groups of the materials and products.

Ring-closing metathesis reaction was used in the total synthesis of marine sponge metabolites, cacospongionolide B (Scheme 7.24) [106]. The intermediate having a 2-alkyl-4-(3-furyl)-3-oxa-1,7-octadiene group undergoes the ring-closing metathesis to form a new six-membered ring in the presence of the Ru catalyst at room temperature. The product is obtained in high yield (81 %) and selectivity, and is further converted to the target compound after four additional reaction steps.

Scheme 7.24

Synthesis of Cacospongionolide B

The total synthesis of epothilone 490 achieved by Danishefsky involved the ring-closing metathesis reaction to form a macrocycle (Scheme 7.25) [107]. The product is obtained in 40 %, and derived to the target compound by removal of the protecting groups. The other possible product with a smaller ring size due to the metathesis of the internal olefin was not formed in the model reactions.

Scheme 7.25

Synthesis of Epothilone 490

The ring-closing metathesis reaction was also employed in the total synthesis of spongidepsin (Scheme 7.26) [108]. The reaction using the Ru catalyst at 110 °C produced the macrocyclic product in 80 %. Hydrogenation of the resulted vinylene group afforded the saturated macrocycle, and one stereoisomer of the products has the same stereochemistry as that of the natural compound.

Scheme 7.26

Synthesis of Spongidepsin

Coleophomones A-D are the functionalized cyclic molecules, and each of them is of interest from the view of pharmacological activity. Nicolaou used the ring-closing metathesis reaction in their total synthesis study [109]. The intermediate with an allyl group at the α-position of the cyclic 1,3-dione (R=H in Scheme 7.27) is converted to the cyclized product having a 11-membered ring (i). The yield is 30 % in spite of the complicated dynamic stereochemistry of the molecule. (E)-Vinylene stereochemistry of the product agrees with the natural product. The starting material remained after the reaction (35 %) was recovered from the reaction mixture. The substrate with two allyl groups at the same carbon forms the compound with a five-membered ring in 85 % yield after 1 h (ii).

Scheme 7.27

Synthesis of Coleophomones

Total synthesis of ciguatoxin CTX3C was achieved by Hirama in 2001 [110–113]. He employed the ring-closing olefin metathesis reaction at almost the final step to form the central nine-membered ring from the diene precursor. The first-generation Grubbs catalyst promoted selective ring-closing reaction at 40 °C without ring-opening of the already existing cyclic olefin groups (Scheme 7.28). The yield of the cyclization, in conjunction with the two preceding reaction steps, attained to 60 %, and deprotection of the product afforded the target molecule.

Scheme 7.28

Ciguatoxin CTX3C

Cross-metathesis reaction is also used in the synthesis of natural organic compounds. The Mo catalyst with a binaphtolate ligand, designed by Schrock, was found to catalyze the cross-metathesis of two 1-olefins to afford the compounds with a cis-vinylene group. The reaction was applied to synthesis of potent immunostimulant KRN7000 (Scheme 7.29) [114]. Cross-metathesis of 1-olefin with the protected allylamine with a sugar substituent (i) yields the product having a cis-vinylene group (ii). cis-Dihydroxylation using OsO₄ forms compound (iii) which is converted to KRN7000 (iv).

Scheme 7.29

Synthesis of KRN7000

Ring-closing metathesis and olefin metathesis reactions are used in synthesis of many other natural products [115–118].

7.3.4 Interlocked Molecules

Interlocked molecules such as catenane (ring and ring) and rotaxane (axle and ring) are expected to behave in a different way from a single molecular compound in the solution, and attract recent research attention. Ring-closing olefin metathesis reaction to yield a large cyclic compound is employed to their formation. Attractive intermolecular interaction between the molecules such as multiple hydrogen bonds and strong π–π interaction etc. stabilizes the intermediate for the formation of the interlocked molecules by enthalpy factors. The reversible nature of the olefin metathesis often enhances the formation of the interlocked molecular systems. Ring closing metathesis reaction of the polyethylene oxide derivative having two terminal vinyl groups in the presence of bis{(3,5-dimethoxy)phenylmethyl}ammonium forms the rotaxane which is stabilized by the O–H···N hydrogen bonding (Scheme 7.30i) [119]. Once-formed rotaxane does not cause detachment of the cyclic and acyclic components owing to too small cavity size of the cyclic component to allow slippage of the bulky 3,5-dimethoxyphenyl group.

Scheme 7.30

Clipping synthesis of rotaxane

Reaction of the crown ether having a C=C bond with bis(benzyl)ammonium forms [2]rotaxane in the presence of catalyst B (Scheme 7.30ii). Repetition of opening of the cyclic compound and its reclosing yields the rotaxane which is stabilized by hydrogen bonding between the ammonium group and oligoethylene oxide groups.

Such macrocycle formation is utilized also to the synthesis of catenane containing the macrocyclic polyethylene oxide having a vinylene group and the macrocyclic dialkylammonium (Scheme 7.31) [120]. Formation of a similar crown ether and its use as the component of pseudo-rotaxane was also reported [121].

Scheme 7.31

Synthesis of catenane

The other strategy for synthesis of the rotaxane is to apply the reversible olefin metathesis reaction to the axle molecule that has a C=C double bond [122]. The molecule is composed of the bulky terminal groups, and functional groups to accommodate the macrocyclic compound and the vinylene group at the center of the oligoethylene chain which binds the terminal groups (Scheme 7.32). Addition of the Ru catalyst to a mixture of the axle and macrocyclic component molecules forms the two fragments of the axle, I and II, which are in equilibrium with the axle molecule by reversible olefin metathesis reactions. The –CH=CH-Ph terminal group of II is able to pass through the cavity of the macrocyclic molecule, and forms a pseudorotaxane. The olefin metathesis of the pseudorotaxane with the fragment I or self-metathesis of II results in the formation of [1]- and [2]-rotaxanes, respectively.

Scheme 7.32

Synthesis of [3]rotaxane via Ru-alkylidene intermediate

Synthesis of the rotaxane using this strategy becomes useful by using the cross-metathesis reactions which binds the two different fragments selectively. Cross-metathesis of terminal alkene with acrylic ester is promoted by the Ru catalyst [96], and the reaction of the pseudorotaxane having an alkenyl terminal group with the bulky acrylic ester forms the rotaxane in high selectivity (Scheme 7.33) [123–128].

Scheme 7.33

End-capping synthesis of rotaxane

Combination of the ring-closing metathesis with the metal template aggregation of the molecules provides an efficient oligoethylene oxide method for the catenane formation (Scheme 7.34) [129, 130]. The macrocycle oligoethylene oxide having 1,10-phenanthroline group and the acyclic compound having the same functional groups and terminal vinyl groups form the tetrahedral Cu(I) complex ((i) in Scheme 7.34). The intramolecular ring-closing metathesis reaction of the two vinyl groups results in the interlocked molecule with the coordination of the Cu(I) center to the two phenanthroline ligand (ii). Further addition of CN⁻ to the solution causes removal of the metal center from the molecular system. The resultant organic part is composed of two macrocyclic molecules interlocked with each other (iii). This strategy is applied to the molecular system which contains the helical stereochemistry within the catenane, a molecular knot [131]. The compound (iv) in Scheme 7.34 is converted to the organic molecular knot by hydrogenation of the vinylene groups and demetalation.

Scheme 7.34

Template synthesis of rotaxane and molecular knots

Preparation of catenane from the two macrocyclic molecules having a vinylene group was also reported [132]. Addition of the Ru catalyst to the solution of the macrocyclic compound in Scheme 7.35 causes formation of the catenane made of the two molecules. The motivation for formation of the entropically unfavorable catenane is in the multiple hydrogen bonds between the functional groups of the cyclic molecules. An amide group of the macrocyclic molecule accepts two O–H···N hydrogen bonds from the amide groups of the other molecule and two N–H···O hydrogen bonds from the ester groups. The equilibrium is shifted to formation of the catenane in a concentrated solution (>95 % in 0.2 M) and to dissociation in a diluted solution (<5 % in 0.0002 M).

Scheme 7.35

Synthesis of catenane from macrocycles

Selective dimer formation of the acyclic diene using the rotaxane template was reported (Scheme 7.36) [133]. The molecules having an aromatic core equipped with two vinyl group-containing substituents and a crown-ether group at 1,3,5-positions form the dimer selectively by intermolecular metathesis reaction of one of the vinyl groups of each molecule.

Scheme 7.36

Dimerization of diene using a rotaxane template

Formation of [3] pseudorotaxane template enhances the dimer formation efficiently.

Addition of a three-armed aromatic compound to three equivalent crown ether molecule having an aromatic pendant with two alkenyl groups in the presence of the Ru catalyst caused cyclotrimerization of the latter molecules via intermolecular olefin metathesis with the aid of the template formation (Scheme 7.37) [134]. Yield of the trimer attains to 55 % when catalyst G is employed.

Scheme 7.37

Cyclotrimerization of diene using a rotaxane template

The dialkylammonium molecule equipped with the oligoethylene oxide acts as the precursor of the daisy-chain type supramolecules [135].

7.4 Conclusion

The olefin metathesis reactions started as the unknown chemical processes, and during the half century, has become indispensable means for synthesis of the polymers, organic and inorganic molecules, and complicated aggregated molecules. It enabled a number of synthetic organic reactions which had been difficult to be achieved. The highly active transition metal catalysts have already reported, and their revision are still continuing. Further progress of this field may enable the novel olefin metathesis catalysis which will change the molecules having olefin groups under the particular kinds of reaction conditions such as in the organs of the living objects.