Metathesis, alkenes

Alkene metathesis, also called olefin metathesis, is a reaction that breaks the strongest bond in an alkene (the double bond) and then rejoins the fragments. When the fragments are joined, each new double bond is formed between two sp carbons that were not previously bonded. Metathesis is a Greek word that means transposition.  

There are two ways in which the fragments can be joined to form a double bond between two sp carbons that were not previously bonded. If the fragments are joined as shown above, then two new alkene products are obtained. If, however, the fragments are joined as shown next, then the starting material is re-formed. All is not lost, however, because the re-formed starting material can undergo another round of metathesis. 

An example of alkene metathesis is shown next. If E and Z isomers are possible for the product of metathesis, both will be formed. 

Metathesis can also be done using two different alkenes as the starting materials. 

If the reactant is a diene, ring-closing metathesis can occur. 

Heterogeneous catalysts were first reported by Eleuterio [3] and the reaction concerned metathesis of light olefins over M0O3 on alumina at high temperature, 160 °C. Heterogeneous applications involve the conversion of 

The Ziegler-like character of the initial catalyst systems prohibited the use of alkenes containing functional groups, even very simple ones as carboxylic esters, amides or ethers, as they will coordinate to the electrophilic metal, or 

In subsequent publications reactions were reported relevant to alkene metathesis, such as 2+2 additions with alkenes giving metallacyclobutanes 

A prerequisite for the a-elimination is the absence of (3-hydrogen atoms in the alkyl groups and this was successfully achieved by using the neopentyl substituents at the metal centre. The nature of the double bond between the metal and carbon was established by its bond length and the occurrence of stereoisomers [13], Typical feature of the Schrock carbenes is that they contain an electrophilic, high-valent metal atom and an electron rich carbene carbon atom. The reverse is true for the older, Fischer carbene compounds, such as the one mentioned, (OC)5W=CPh2. 

Involvement of a-elimination reactions for in situ prepared catalysts from WC16 and Me4Sn was demonstrated by the use of 13C in tetramethyltin. The norbomene polymers formed contained the 13CH2 alkene moiety as the end-group. Also unstable C14W=CH2 and Cl4W=13CH2 species were observed by H NMR spectroscopy [14], 

The reaction in which two alkenes exchange their alkylidene fragments is called alkene metathesis. The synthesis of libraries in liquid- and solid-phase employing this kind of C-C bond formation has been reported. There are three types of me- 

The combination of ring opening and ring closing metathesis is used for the synthesis of polycyclic structures by Lee et al. [265]. The metathesis on solid-phase includes not only the chemical transformation of resin bound intermediates but as well as the cleavage of final products from the support [181]. 

Many of the leading workers in this field participated in the Lyon symposium on the subject.The mechanism of alkene metathesis proceeds through a metallocyclobutane derivative formed by reaction of an alkene with a metal-carbene complex. Retro-carbene addition yields a product molecule and a new carbene 

In general Fischer-type carbene complexes are catalytically inactive but there are various means of converting them into active carbenes. Thus nucleophilic attack by CHsLi in 1 at the carbene carbon followed by removal of the 

Homogeneous Catalysis of Organic Reactions by Complexes of Metal Ions 

A series of alkylidenetantalum(V) complexes has provided considerable insight into another type of activation process in metathesis catalysis. Thus benzyl and neopentyl complexes undergo a abstraction, the more hindered neopentyl complex the more readily. Treatment with an excess of phosphine [L = P(CH3)3] gives a abstraction in a very hindered seven-coordinate species [TaL2(CH2C(CH3)3)2Cl3]. Nmr studies show a complicated series of dissociation and dimerization equilibria among carbene complexes of the type [TaL (CHC(CH3)3)Cl3] with n = and a full account of metathesis catalysis 

Some possible termination steps are easily identified in the slow reactions of tantalum complexes such as [Ta(C5H5)(CHC(CH3)3)Cl2] and [TaL2(CHC(CH3)3)Cl3] (7a) and (7b) (L = P(CH3)3). Addition of RCH=CH2 

In this transformation, the C=C bond of an alkene such as RCH=CHR is broken with the resulting RHC and R HC fragments being redistributed (Eq. 12.1). Originally developed in industry, metathesis could at first 

The Organometallic Chemistry of the Transition Metals, Sixth Edition. Robert H. Crabtree. 

To make catalysts more tolerant of functionality, a move to the right in the periodic table became necessary. The early titanium catalysts are least tolerant because they react preferentially with heteroatom functionalities in the order  

Rhodium is too far to the right and fails to give metathesis—the key carbene intermediate instead undergoes RE to give cyclopropanes. Grubbs Ru catalysts (12.1) have proved to be the easiest to handle, but some applications require Schrock s more reactive Mo catalysts (12.2). Both contain the critical metal carbene unit required for catalysis. 

Metatheses naturally divide into types, depending on the substrates and products. Beyond simple metathesis (Eq. 12.1) involving a single alkene as reactant, comes cross metathesis (CM, Eq. 12.2), where two different alkenes react. In a common variant of CM, one product is removed, such as volatile C2H4 in Eq. 12.2, to drive the reaction to the 

Herve Clavier and Steven P. Nolan, now at St. Andrew s University, found (Adv. Synth. Cat. 2008, 550, 2959) that the indenylidene Ru complex 1 was an excellent pre-catalyst for alkene metathesis. A combination of 1 and the ligand 2 effected cross metathesis of 3 and 4 in just 15 minutes under microwave heating. Robert H. Grubbs of Caltech designed Organic Lett. 2008, i 0, 2693) the Ru catalyst 6 for the preparation of tri- and tetrasubsti-tuted alkenes, as illustrated by the conversion of 7 to 8. The catalyst 6 also worked well for cross metathesis and ring opening metathesis pol nnerization (ROMP). 

For some biological applications, it would be desirable to run alkene cross metathesis under aqueous conditions. Benjamin G. Davis of the University of Oxford observed (/. Am. Chem. Soc. 2008,130, 9642) that aUyl sulfides such as 9 were unusually reactive in cross metathesis. Indeed, aqueous cross methathesis with such an aUyl sulfide incorporated in a protein woiked well, although added MgClj was required. The protein, a serine protease, maintained its activity after cross metathesis. 

Although alkene metathesis is often run in CH Cl, benzene or toluene, these are not necessarily the optimal solvents. Siegfiied Blechert of the TU Berlin established Tetrahedron Lett. 2008, 49, 5968) that for the difficult cyclization of 16 to 17, hexafluo-robenzene worked particularly well. 

Su Seong Lee and Jackie Y. Yingofthe Institute of Bioengineering andNanotechnology, 

Singapore, constructed (Chem. Commun. 2008, 4312) the metathesis catalyst 22, covalently bound to siliceous mesocellular foam. At 5% catalyst loading, the tenth cycle for the cyclization of 23 to 24 gave the same yield as the first cycle, 97%. Ru residues in solution 

The Organometallic Chemtttry of Ae Transition Meteds, Fourth Edition, by Robert H. Crabtree Copyright 2005 John Wil Sons, Inc. 

The final products are statistical unless the reaction can be driven in some way such as by continuous removal of a volatile product like C2H4 (Eq. 12.2). 

Metathesis can usefully be divided into a number of types, depending on the nature of the substrates and products in the catalytic reaction. A reaction such as Eq. 12.1 is a sinq te metathesis. With two substrates we have the reverse version, a cross metathesis (Eq. 12.3). With some choices of R and R the cross product can be favored kinetically. This happens in Eq. 12.4 wh e one alkene, r-BuCH=CH2, present in excess, is too bulky to metathesize with itself, and the cross product is formed in 93% yield.  

With a conjugated diene, ring-closing metathesis (RCM) is often possible, particularly where the product ring is unstrained (Eq. 12.5). The reverse of 

4 is a ring-opening metathesis (ROM), favored by the presence of a large excess of C2H4. 

The formation of a Schiff base through condensation of a primary amine with an aldehyde or ketone has recently found application in the construction of 

Because of the many possible reactions of aldols, it is generally recommended to use a freshly distilled product for further synthetic steps. 

Besides the aldol reaction in the true sense, there are several other analogous reactions, where some enolate species adds to a carbonyl compound. Such reactions are often called aldol-type reactions the term aldol reaction is reserved for the reaction of aldehydes and ketones. 

Wittig, H. Reiff, Angew. Chem. 1968, 80, 8-15 Angew. Chem. Int. Ed. Engl. 

Heathcock in Modern Synthetic Methods 1992 (Ed. R. Scheffold), VHCA, Basel, 1992, p. 1-102. 

Exchange of alkylidene groups of alkenes—metathesis of olefins 

Surface organometallic and related molecular species Propene Ethyl oleate Reference 

Ivtol of substrate (mol of catalyst) s , after 5 min in batch reactions at 25 °C. 

OSiHs) [82] found that the unsymmetrical catalysts (X Y) are systematically more efficient for all systems (W, Mo and Re). Overall, Mo and W catalysts are more efficient due to the presence of the imido ligand, because it favors distortion of the initial complexes, except when X Y-in this case, all systems are equally efficient [81], 

Recent developments have been reported for imido-molybdenum systems. When X = 2,5-dimethylpyrrolyl, more stable surface species can be obtained (although a second minor species, formed by the addition of a surface hydroxyl group to the alkylidene ligand, is also present). Moreover, by tuning the imido ligand, the catalytic activity has been improved dramatically (Table 11.3, bottom rows) [20]. 

For all these well-defined catalysts, the initiation step corresponds to the crossmetathesis of the olefin and the neopentylidene ligand. When the olefin is propene. 

When a mixture of alkenes 1 and 2 or an unsymmetrically substimted alkene 3 is treated with an appropriate transition-metal catalyst, a mixmre of products (including E/Z-isomers) from apparent interchange of alkylidene moieties is obtained by a process called alkene metathesis.With the development of new catalysts in recent years, alkene metathesis has become a useful synthetic method. Special synthetic applications are, for example, ring-closing metathesis (RCM) and ring-opening metathesis polymerization (ROM) (see below). 

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Ethers, esters, amides and imidazolidines containing an epithio group are said to be effective in enhancing the antiwear and extreme pressure peiformance of lubricants. Other uses of thiiranes are as follows fuel gas odorant (2-methylthiirane), improvement of antistatic and wetting properties of fibers and films [poly(ethyleneglycol) ethers of 2-hydroxymethyl thiirane], inhibition of alkene metathesis (2-methylthiirane), stabilizers for poly(thiirane) (halogen adducts of thiiranes), enhancement of respiration of tobacco leaves (thiirane), tobacco additives to reduce nicotine and to reduce phenol levels in smoke [2-(methoxymethyl)thiirane], stabilizers for trichloroethylene and 1,1,1-trichloroethane (2-methylthiirane, 2-hydroxymethylthiirane) and stabilizers for organic compounds (0,0-dialkyldithiophosphate esters of 2-mercaptomethylthiirane). The product of the reaction of aniline with thiirane is reported to be useful in the flotation of zinc sulfide. 

Alkanes, dipurin-8-yl-synthesis, 5, 574 Alkanes, poly-N-pyrazoIyl-synthesis, 5, 320 Alkanoic acids, tetrazolyl-anti-inflammatory activity, 5, 835 Alkanoic acids, 4-thienyi-cyclization, 4, 905-906 Alkene metathesis mechanism, 1, 668 Alkenes activated... 

M(C 0)s and other Mo and W compounds catalyse alkene metathesis hy the formation of... 

Alkene metathesis for the synthesis of carbo- and heterocyclic compounds 97YGK1101. 

The synthetic utility of the alkene metathesis reaction may in some cases be limited because of the formation of a mixture of products. The steps of the catalytic cycle are equilibrium processes, with the yields being determined by the thermodynamic equilibrium. The metathesis process generally tends to give complex mixtures of products. For example, pent-2-ene 8 disproportionates to give, at equilibrium, a statistical mixture of but-2-enes, pent-2-enes and hex-3-enes ... 

By analogy to the alkene metathesis, this reaction sequence is called 1,3-dipol metathesis. 

Acyclic alkadienes, metathesis of, 134 Acyclic alkenes, metathesis reaction of, 133, 134... 

These carbene (or alkylidene) complexes are used for various transformations. Known reactions of these complexes are (a) alkene metathesis, (b) alkene cyclopropanation, (c) carbonyl alkenation, (d) insertion into C-H, N-H and O-H bonds, (e) ylide formation and (f) dimerization. The reactivity of these complexes can be tuned by varying the metal, oxidation state or ligands. Nowadays carbene complexes with cumulated double bonds have also been synthesized and investigated [45-49] as well as carbene cluster compounds, which will not be discussed here [50]. 

Fiirstner A (1998) Alkene metathesis in organic synthesis (Topics in organometallic chemistry I). Springer, Berlin Heidelberg New York... 

Fig. la—d Typical alkene metathesis reactions ring-closing (RCM) and ring-opening (ROM) metathesis (a), diene cross metathesis (CM, b), ROM-RCM (c), and ROM-double RCM (d) sequences (ring-rearrangement reactions, RRM)... 

Treatment of the 1,2-oxazines 52 with carbon monoxide at 1000 psi in the presence of cobalt carbonyl brings about insertion of carbon monoxide to form the 1,3-oxazepines S3 <96TL2713>. A convenient route to P-lactams fused to oxepines is made available by alkene metathesis. Thus reaction of 4-acetoxyazetidin-2-one with ally alcohol in the presence of zinc acetate, followed by iV-allylation of the nitrogen affords the derivative 54 which cyclises by RCM to form the oxazepinone 55 <96CC2231>. The same communication describes a similar synthesis of 1,3-dioxepines. 

Two RCM reactions were employed in a new and efficient route to a key chiral intermediate, isoquinuclidine 150, in the synthesis of alkaloid (-F)-catharanthine <06AG(I)5334>. The first RCM makes use of chiral enone 151, derived from L-serine, to generate a chiral dihydropyridinone 152. Intramolecular alkene metathesis of dialkenyl piperidine 153 generates 150, which represents the first example of the use of RCM in the generation of an azabicyclo[2.2.2]alkene system. 

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