Intermolecular metathesis

Acyclic diene molecules are capable of undergoing intramolecular and intermolec-ular reactions in the presence of certain transition metal catalysts molybdenum alkylidene and ruthenium carbene complexes, for example [50, 51]. The intramolecular reaction, called ring-closing olefin metathesis (RCM), affords cyclic compounds, while the intermolecular reaction, called acyclic diene metathesis (ADMET) polymerization, provides oligomers and polymers. Alteration of the dilution of the reaction mixture can to some extent control the intrinsic competition between RCM and ADMET. 

The metathesis of acyclic alkadienes and higher polyenes may involve both inter- and intramolecular processes. An example of an intermolecular reaction is the conversion of 1,5-hexadiene into 1,5,9-decatriene and ethene ... 

It has been suggested that these polymers are mainly linear, which may be a consequence of intermolecular metathesis reactions with traces of acyclic alkenes, or of other consecutive reactions 19-22). 

Non-heteroatom-stabilised Fischer carbene complexes also react with alkenes to give mixtures of olefin metathesis products and cyclopropane derivatives which are frequently the minor reaction products [19]. Furthermore, non-heteroatom-stabilised vinylcarbene complexes, generated in situ by reaction of an alkoxy- or aminocarbene complex with an alkyne, are able to react with different types of alkenes in an intramolecular or intermolecular process to produce bicyclic compounds containing a cyclopropane ring [20]. 

As stated above, olefin metathesis is in principle reversible, because all steps of the catalytic cycle are reversible. In preparatively useful transformations, the equilibrium is shifted to one side. This is most commonly achieved by removal of a volatile alkene, mostly ethene, from the reaction mixture. An obvious and well-established way to classify olefin metathesis reactions is depicted in Scheme 2. Depending on the structure of the olefin, metathesis may occur either inter- or intramolecularly. Intermolecular metathesis of two alkenes is called cross metathesis (CM) (if the two alkenes are identical, as in the case of the Phillips triolefin process, the term self metathesis is sometimes used). The intermolecular metathesis of an a,co-diene leads to polymeric structures and ethene this mode of metathesis is called acyclic diene metathesis (ADMET). Intramolecular metathesis of these substrates gives cycloalkenes and ethene (ring-closing metathesis, RCM) the reverse reaction is the cleavage of a cyclo-... 

Dienes can react intermolecularly or intramolecularly. Intermolecular reactions generate rings, usually alkenes or dienes. Alkenes methasis can be used to form very large rings, including 21-membered lactone rings. Metathesis with vinyl-cyclo-... 

The olefin cross metathesis (CM) can be described as the intermolecular metathesis of alkylidene fragments between two different olefins [133]. It can be farther divided into three main subtypes cross metathesis, ring opening cross metathesis (ROCM) and enyne cross metathesis (ECM) (Scheme 3.9). 

Intermolecular metathesis Ring-closing metathesis Ring-opening metathesis... 

Olefin metathesis can also be used in intermolecular reactions.299 For example, a variety of functionally substituted side chains were introduced by exchange with the terminal double bond in 5.300 These reactions gave E Z mixtures. 

The effectiveness of these intermolecular reactions depends on the relative reactivity of the two components, since self-metathesis leading to dimeric products will occur if one compound is more reactive than the other. 

Triple bonds can also participate in the metathesis reaction. Intramolecular reactions give vinylcycloalkenes, whereas intermolecular reactions provide conjugated dienes.301 The mechanism is similar to that for a, to-diene metathesis, but in contrast Reactions involving to diene cyclization, no carbon atoms are lost.302... 

Another intramolecular ene-yne metathesis followed by an intermolecular metathesis with an alkene to give a butadiene which is intercepted by a Diels-Alder reaction was used for the synthesis of condensed tricyclic compounds, as described by Lee and coworkers [266]. However, as mentioned above, the dienophile had to be added after the domino metathesis reaction was completed otherwise, the main product was the cycloadduct from the primarily formed diene. Keeping this in mind, the three-component one-pot reaction of ene-yne 6/3-94, alkene 6/3-95 and N-phenylmaleimide 6/3-96 in the presence of the Grubbs II catalyst 6/3-15 gave the tricyclic products 6/3-97 in high yield (Scheme 6/3.28). 

Murakami and coworkers [267] described a combination of an intermolecular ene-yne metathesis followed by a disrotatory 6ir-electrocyclic reaction to give six-membered cyclic dienes. Thus, reaction of 6/3-98 and of styrene (6/3-99) in the presence of a ruthenium catalyst at 100 °C led to the condensed cyclohexadienes 6/3-100, in good yield (Scheme 6/3.29). 

Intermolecular metathesis of linseed and soybean oils, which are triglycerides of linoleic and linolenic acids, offers an alternative method of upgrading these drying oils into stand oils by a net increase of their molecular weights. 

Three novel stereo- and regioselective schemes for the total synthesis of (+ )-brefeldin A 440 have been accomplished. Each of them exploit intermolec-ular nitrile oxide cycloaddition for constructing the open chain and introducing substituents, but differ in subsequent stages. The first (480) and the second (481) use intramolecular cycloaddition for the macrocycle closure. However, in the second scheme INOC is followed by C=C bond cis-trans-isomerization. In the third scheme (481) intermolecular cycloaddition is followed by ring closing metathesis as the key step. 

In addition to transition metals, recent work has demonstrated that strong Lewis acids will catalyze the addition of silanes to alkynes in both an intra- and an intermolecular fashion.14,14a-14c The formation of vinylsilanes from alkynes is possible by other means as well, such as the synthetically important and useful silylcupration15,15a of alkynes followed by cuprate protonation to afford vinylsilanes. These reactions provide products which can be complementary in nature to direct hydrometallation. Alternatively, modern metathesis catalysts have made possible direct vinylsilane synthesis from terminal olefins.16,16a... 

Grubbs has reported a similar tandem olefin metathesis-carbonyl olelination process for the preparation of cyclic olefins [31]. In this case, treatment of a keto-olefin with the molybdenum alkylidene 1 at 20°C generates an intermediate alkylidene complex. Under these conditions, competing intermolecular olelination does not occur. However, intramolecular carbonyl olelination of the initially formed alkylidene complex can occur and this results in the formation of a cyclic olefin. This tandem sequence is illustrated by the transformation of keto-olefins... 

Intermolecular Carbonyl Olefination and Subsequent Ring-Closing Metathesis... 

Enyne metathesis is unique and interesting in synthetic organic chemistry. Since it is difficult to control intermolecular enyne metathesis, this reaction is used as intramolecular enyne metathesis. There are two types of enyne metathesis one is caused by [2+2] cycloaddition of a multiple bond and transition metal carbene complex, and the other is an oxidative cyclization reaction caused by low-valent transition metals. In these cases, the alkyli-dene part migrates from alkene to alkyne carbon. Thus, this reaction is called an alkylidene migration reaction or a skeletal reorganization reaction. Many cyclized products having a diene moiety were obtained using intramolecular enyne metathesis. Very recently, intermolecular enyne metathesis has been developed between alkyne and ethylene as novel diene synthesis. 

The metathesis reaction is a powerful strategy in synthetic organic chemistry [1], and it is generally accepted that this reaction is catalyzed by highly efficient transition metal alkylidenes [2, 3]. Intermolecular diene metathesis produces... 

Intermolecular-enyne metathesis, if it is possible, is very unique because the double bond of the alkene is cleaved and each alkylidene part is then introduced onto each alkyne carbon, respectively, as shown in Scheme 9. If metathesis is carried out between alkene and alkyne, many olefins, dienes and polymers would be produced, because intermolecular enyne metathesis includes alkene metathesis, alkyne metathesis and enyne metathesis. The reaction course for intermolecular enyne metathesis between a symmetrical alkyne and an unsym-metrical alkene is shown in Scheme 9. The reaction course is very complicated, and it seems impossible to develop this reaction in synthetic organic chemistry. 

Intermolecular enyne metathesis has recently been developed using ethylene gas as the alkene [20]. The plan is shown in Scheme 10. In this reaction,benzyli-dene carbene complex 52b, which is commercially available [16b], reacts with ethylene to give ruthenacyclobutane 73. This then converts into methylene ruthenium complex 57, which is the real catalyst in this reaction. It reacts with the alkyne intermolecularly to produce ruthenacyclobutene 74, which is converted into vinyl ruthenium carbene complex 75. It must react with ethylene, not with the alkyne, to produce ruthenacyclobutane 76 via [2+2] cycloaddition. Then it gives diene 72, and methylene ruthenium complex 57 would be regenerated. If the methylene ruthenium complex 57 reacts with ethylene, ruthenacyclobutane 77 would be formed. However, this process is a so-called non-productive process, and it returns to ethylene and 57. The reaction was carried out in CH2Cl2 un-... 

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