Alkene metathesis intermolecular

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. 

Dienes are cyclized by intramolecular metathesis. In particular, cyclic alkenes 43 and ethylene are formed by the ring-closing metathesis of the a,co-diene 46. This is the reverse reaction of ethenolysis. Alkene metathesis is reversible, and usually an equilibrium mixture of alkenes is formed. However, the metathesis of a,co-dienes 46 generates ethylene as one product, which can be removed easily from reaction mixtures to afford cyclic compounds 43 nearly quantitatively. This is a most useful reaction, because from not only five to eight membered rings, but also macrocycles can be prepared by RCM under high-dilution conditions. However, it should be noted that RCM is an intramolecular reaction and competitive with acyclic diene metathesis polymerization (ADMET), which is intermolecular to form the polymer 47. In addition, the polymer 47 may be formed by ROMP of the cyclic compounds 43. 

Dienes can react intermolecularly or intramolecularly. Intramolecular reactions generate rings, usually alkenes or dienes. Alkene metathesis can be... 

Ri r3 In an alkene metathesis two alkenes react with an appropriate catalyst to form two new alkenes. There are different types of alkene pj2 r4 metathesis reactions The intermolecular reaction is called cross metathesis (CM), whereas intramolecular metathesis is divided into ring-closing metathesis (RCM) and ring-opening metathesis (ROM). Also two polymerization versions of alkene metathesis exist metathesis polymerization of acyclic dienes and ring-opening metathesis polymerization (ROMP). 

The total synthesis of the potent anticancer macrocyclic natural product lasiodiplodin was achieved in the laboratory of A. Furstner. The key macrocyclization step was carried out by the alkene metathesis of a styrene derivative, which was prepared in excellent yield via an intermolecular Heck reaction between an aryl triflate and high-pressure ethylene gas. 

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-... 

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). 

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. 

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-... 

Intermolecular olefin metathesis starts to compete with traditional C=C-bond forming reactions such as the Wittig reaction and its modifications, as illustrated by the increasing use of electron-deficient conjugated alkenes for the ( )-selective construction of enals and enoates. 

Blechert et al. succeeded in intermolecular CM of terminal alkyne and terminal alkene. A reaction carried out in CH2CI2 at RT in the presence of 5-7mol% Ic gives a mixture of ( )- and (Z)-isomers (Table 2). Because of the nonselective stereochemical course, a silyl-protected ally alcohol is employed and the resulting metathesis product is deprotected and oxidized to afford the desired diene having an -configuration (Equation (13)). 

Macrolactone synthesis 6,51, 71, 72, 94, 124,131,163,187,195 McMurry coupling 43 Medium ring synthesis 43,45,75, 77 Metathesis, Alkene (see Grubbs) Metathesis, Alkyne (see alkyne metathesis) Michael addition Intramolecular 166,166, 167,201 Intermolecular 57,84, 153, 166,204... 

Mechanistic studies of the rearrangement activity of the ring-opening metathesis polymerization catalyst [Ru(H20)6]2+ were reported for unfunctionalized alkenes (112). The mechanism was found to be intermolecular, the alkene isomerization proceeding through an addition-elimination mechanism with a metal hydride catalytic species. This interpretation was... 

Until recently, intermolecular enyne metathesis received scant attention. Competing CM homodimerisation of the alkene, alkyne metathesis and polymerisation were issues of concern which hampered the development of the enyne CM reaction. The first report of a selective ruthenium-catalysed enyne CM reaction came from our laboratories [106]. Reaction of various terminal alkynes 61 with terminal olefins 62 gave 1,3-substituted diene products 63 in good-to-excellent yields (Scheme 18). It is interesting that in these and all enyne CM reactions subsequently reported, terminal alkynes are more reactive than internal analogues, and 1,2-substituted diene products are never formed thus, in terms of reactivity and selectivity enyne CM is the antithesis of enyne RCM. The mechanism of enyne CM is not well understood. It would appear that initial attack is at the alkyne however, one report has demonstrated initial attack at the alkene (substrate-dependent) is also possible, see Ref. [107]. 

Intermolecular enyne (ene-yne) metathesis combines an alkene and an alkyne into a 1,3-diene (Eq. 54). 

The intermolecular enyne cross metathesis, and consecutive RCM, between a terminal alkyne and 1,5-hexadiene produces cyclohexadienes, by cascade CM-RCM reaction, and trienes, formed during the sole CM step. Studies of various parameters of the reaction conditions did not show any improvement of the ratio of desired cyclohexadiene product [25] (Scheme 12). The reaction with cyclopentene instead of hexadiene as the alkene leads to 2-substituted-l,3-cycloheptadienes [26]. After the first cyclopentene ROM, the enyne metathesis is favored rather than ROMP by an appropriate balance between cycloalkene ring strain and reactivity of the alkyne. 

Diynes are also used to perform intermolecular enyne metathesis. With the objective of producing functionalized hetero- and carbocycles, a cascade diyne-alkene cross metathesis leading to five-membered cyclic products has recently been proposed [27] (Scheme 13). 

Unsaturated polymers can be produced by means of ring-opening metathesis polymerization (ROMP) of cyclic alkenes. These unique polymers can also be produced via intermolecular Acyclic Diene Metathesis (ADMET). Dienes can also react intramolecularly via Ring Closing Metathesis (RCM) to afford cyclic products. RCM is often applied to synthesis of compounds for fine chemical and pharmaceutical application. Generic examples of these reactions are shown in Figure 2. 

Cyclobutadiene iron tricarbonyl complexes can be isolated and have been utilized in organic synthesis. Both intra- and intermolecular [2 + 2] cycloadditions of alkenes with cyclobutadiene complexes are observed upon decomplexation using CAN or TMANO (Schemes 164-165). The stereochemistry of the aUcene is retained in the product. Iron tricarbonyl diene complexes are compatible with metathesis reactions... 

It was recognized early that efficient olefin cross metathesis could provide new methods for the synthesis of complex molecules. However, neither (la) nor (2a) were very effective at intermolecular cross metathesis owing to poor reaction selectivity (cross vs. intramolecular metathesis) and low E. Z ratios see (E) (Z) Isomers) The advent of more active and functional group tolerant olefin metathesis catalysts recently made cross metathesis a viable route for constructing a large variety of fimctionalized acyclic alkenes. 

The metathesis of acyclic alkadienes and polyenes may follow an inter- or intramolecular pathway. The intramolecular metathesis of an a,tfi-diene yields ethylene and a cyclic alkene, while the intermolecular reaction results primarily in the formation of ethylene and a symmetric triene (eq. (2)). The loss of a small molecule like ethylene serves to drive the equilibrium to the product side. 

The most likely scenario for enyne metathesis is an intramolecular combination of the alkene and alkyne moieties to form a ring, which is really a variation of RCM. Examples of intermolecular enyne metathesis (CM) have been successful if they are run in an atmosphere of ethene, using it as the alkene component. Even for some intramolecular enyne metatheses, preequilibration of the catalyst with ethene caused vastly improved yields.74 Equations 11.2475 and 11.2576 show... 

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