Metathesis intramolecular

Another interesting transformation is the intramolecular metathesis reaction of 1,6-enynes. Depending on the substrates and catalytic species, very different products are formed by the intramolecular enyne metathesis reaction of l,6-enynes[41]. The cyclic 1,3-diene 71 is formed from a linear 1,6-enyne. The bridged tricyclic compound 73 with a bridgehead alkene can be prepared by the enyne metathesis of the cyclic enyne 72. The first step of... 

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-... 

Catalysts with an unsymmetrical NHC ligand featuring a vinylic side chain have the unique ability to metathesise their own ligand to form a metaUacycle as shown in Scheme 3.7 [119], Ring opening metathesis will then incorporate the monomers, e.g. cyclooctene, into that cycle until a cyclic polymer is cleaved by another intramolecular metathesis step. The catalyst is recovered and can restart this endless route to cyclic polymers [121]. 

Scheme 3.7 REMP Intramolecular metathesis of pre-catalyst 75 to form catalyst 76 incorporation of monomers, release of a cyclic polymer and catalyst recovery...

Tungsten aryloxo complexes have been shown to catalyze the intramolecular metathesis reactions of di- and tri-substituted co-unsaturated glucose and glucosamine derivatives to yield bicyclic carbohydrate-based compounds containing 12- and 14-membered rings [108,214,215]. An example is shown in Eq. 37. The tolerance for amides and esters is noteworthy, as are the yields and the size of the rings that are formed. 

The key step in Fiirstner s elegant synthesis of racemic 153 furnishing a Z E=7 3 mixture, used an intramolecular metathesis reaction of the ester A [292]. Employing optically active 9-decene-2-ol will certainly produce the desired enantiomer (Fig. 7). 

Starting from substituted 2-azetidinones, a family of tribactams (II, Fig. 7) has been reported to be prepared by using two main steps an intramolecular metathesis reaction and a Diels-Alder cyclization [258],... 

A further confirmation of the metal carbene mechanism is provided by enyne intramolecular metathesis reactions such as that depicted in equation 61. The C=C bond in the substrate becomes the single bond attaching the alkenyl group to the phenanthrene ring system634,635. 

Enyne intramolecular metathesis reactions, of the type shown in equation 61, can be very useful in organic synthesis. A number of such reactions, catalysed by tungsten or chromium carbene complexes, have been reported634,635,737 - 740. The ruthenium carbene catalysts 18-20 (Table 2) are likely to be increasingly used for this purpose because of their stability, ease of handling and good yields, as in the synthesis of various 5-, 6- and 7-membered heterocycles, e.g. equation 67741. 

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. 

Intramolecular metathesis of the cyclic-acyclic diene 48 affords the rearranged products 50 by reconstruction of the ring via 49. 

Intramolecular metathesis of dienes leads to ring-closing metathesis (RCM), offering a useful synthetic route to cyclic compounds. The Ru and Mo catalysts are extremely useful for RCM of dienes as a synthetic method for cycloalkenes, cylic ethers and... 

The six-membered ring 85 is obtained from the allylamine 84 [31]. The sulfur-containing ring 87 was obtained from 86 using the Mo catalyst. The Ru catalyst is not active for this reaction [32]. The (S, f )-chromene derivative 89 was obtained in 97% yield by the Mo-catalysed intramolecular metathesis of (S,f )-cycloheptenyl styrenyl ether 88 under an atmosphere of ethylene. In the absence of ethylene, 89 and its dimer were obtained. The enantioselective total synthesis of (.S, / ,/ , / )-ncbivoIoI (90) has been carried out from 89 [33]. No cyclization of the cyclopentene 91 was observed, because the highly strained cyclobutane intermediate 92 is difficult to form. 

Preparation of macrocyclic compounds Development of efficient RCM, catalysed by Ru and Mo complexes, has revolutionized the synthesis of macrocyclic compounds. As an early example of RCM, intramolecular metathesis of oleyl oleate (104) using WC16 — Cp2TiMe2 afforded the 19-membered lactone 105, although yield was not satisfactory [20]. 

Reaction of the carbene complex 148 with alkyne affords vinylcarbene 150 via metallacyclobutene 149. In the intramolecular reaction of enyne 152, catalysed by carbene complex 151, the triple bond is converted to vinylcarbene 153 which then reacts with the double bond to give the conjugated diene 154. Generation of 154 is expected by the formation and cleavage of cyclobutene 155 as a hypothetical intermediate. Based on this reaction, Ru-catalysed intramolecular metathesis of enyne 156 gave the N-containing cyclic diene 157, from which (—)-stemoamide (158) was synthesiszed. The reaction can be understood by assuming the formation of the hypothetical cyclobutene 159 from 156 [52],... 

Cleavage via alkene metathesis is particularly useful because clean and selective scissoring of molecules is possible. Cleavage by metathesis can be performed either by cyclization during cleavage [95-101] (ring closing metathesis, RCM), inter-molecular metathesis [101] (cross metathesis), or intramolecular metathesis [95] (Scheme 6.1.23). 

In the ring-closing metathesis reaction, intramolecular metathesis closes a ring to form a small cyclic molecule with concurrent loss of a small molecule (ethylene). Conversely, in the case of the acyclic diene metathesis reaction, macromolecules are formed by successive intermolecular condensation of two olefinic molecules [1],... 

Basset s catalyst was also used for the intramolecular metathesis of diluted solutions of di- and tri-substituted w-unsaturated glucose and glucosamine derivatives, affording bicyclic carbohydrate-based structures in reasonable yields (Equations (119)—(122)).141... 

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. 

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 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. 

Reaction of bis(disilanyl)dithiane 32 with the corresponding palladium(O)-isonitrile complex affords a four-membered cyclic bis(silyl)palladium(II) complex 34 quantitatively together with the formation of a disilane (Eq. 15) [30]. The formal intramolecular metathesis of the two Si-Si bonds of 32 may proceed through initial formation of tetrakis(silyl)Pd(IV) complex, corresponding to the platinum complex 33. The double oxidative addition of the two Si-Si bonds may be followed by reductive elimination of the disilane with accompanying formation of four-membered bis(silyl)palladium complex 34, due to difficulty in reductive elimination leading to formation of a three-membered cyclic disilane. 

Without question, intramolecular metathesis reactions dominate synthetic applications and alkenes containing a =CH2 unit are commonly used so that one product is ethylene, which escapes from the reaction medium and drives the equilibrium toward the desired cyclized product. A representative example is taken from the Omura, Smith et al. synthesis of (-(-)-madindoline in which diene 427 was treated with 0.2... 

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