Triple metathesis

The metathesis of linear alkynes has also been reported, e.g. the metathesis of propyne, 1-pentyne, 2-pentyne, and 2-hexyne (31-33). This reaction can be visualized as the cleavage and formation of carbon-carbon triple bonds ... 

An obvious drawback in RCM-based synthesis of unsaturated macrocyclic natural compounds is the lack of control over the newly formed double bond. The products formed are usually obtained as mixture of ( /Z)-isomers with the (E)-isomer dominating in most cases. The best solution for this problem might be a sequence of RCAM followed by (E)- or (Z)-selective partial reduction. Until now, alkyne metathesis has remained in the shadow of alkene-based metathesis reactions. One of the reasons maybe the lack of commercially available catalysts for this type of reaction. When alkyne metathesis as a new synthetic tool was reviewed in early 1999 [184], there existed only a single report disclosed by Fiirstner s laboratory [185] on the RCAM-based conversion of functionalized diynes to triple-bonded 12- to 28-membered macrocycles with the concomitant expulsion of 2-butyne (cf Fig. 3a). These reactions were catalyzed by Schrock s tungsten-carbyne complex G. Since then, Furstner and coworkers have achieved a series of natural product syntheses, which seem to establish RCAM followed by partial reduction to (Z)- or (E)-cycloalkenes as a useful macrocyclization alternative to RCM. As work up to early 2000, including the development of alternative alkyne metathesis catalysts, is competently covered in Fiirstner s excellent review [2a], we will concentrate here only on the most recent natural product syntheses, which were all achieved by Fiirstner s team. 

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... 

One problem in the combination of metathesis transformations using alkenes is the fact that they are equilibrium reactions. In contrast, metathesis reactions of ene-ynes are irreversible as they give 1,3-butadienes, which are usually inert under the reaction conditions. Thus, the combination of a RCM and a ROM of ene-ynes of type 6/3-48 in the presence of an alkene (e. g., ethylene) led to 6/3-49 in good yield (Scheme 6/3.13) [242]. In these transformations the terminal triple bond reacts first. The process is not suitable for the formation of six-ring heterocycles. 

Molybdenum imido alkylidene complexes have been prepared that contain bulky carboxylate ligands such as triphenylacetate [35]. Such species are isola-ble, perhaps in part because the carboxylate is bound to the metal in an r 2 fashion and the steric bulk prevents a carboxylate from bridging between metals. If carboxylates are counted as chelating three electron donors, and the linear imido ligand forms a pseudo triple bond to the metal, then bis(r 2-carboxylate) species are formally 18 electron complexes. They are poor catalysts for the metathesis of ordinary olefins, because the metal is electronically saturated unless one of the carboxylates slips to an ri1 coordination mode. However, they do react with terminal acetylenes of the propargylic type (see below). 

In the first structurally characterized complexes of type A the metal-phosphorus triple bonds are kinetically stabilized by bulky substituents at the amido ligands. Therefore, these compounds reveal exclusively end-on reactivity via the phosphorus lone pair. This reactivity pattern seems also valid for the solution stable alkoxide derivative [(C/0)3Mo=P], for which the reaction potential is under investigation [13]. In contrast, due to their lesser degree of kinetic stabilization by bulky substituents the short-lived alkoxide containing complexes [(R 0)3W=Pj (R =t-Bu (3c), Ph (3d)), generated by the metathesis reaction between the alkoxide-dimer and the phosphaalkyne (cf. Eq. 8), show additionally a high side-on reactivity towards the phos-phaalkynes of the reaction mixture. Thus, there occurs a formal cycloaddition reaction with the phosphaalkynes, and a subsequent 1,3-OR shift yields the formation of four-membered diphospha-metallo-cyclobutane derivatives 6(Eq. 8) [15,31, 37]. 

Metathesis of W2(OBu )e with one C=C triple bond of substituted 1,4-diethynylbenzenes has given carbyne complexes which can be converted into trans-WCl(=CC6H4C=CH)(dmpe)2. Functionalization via the W—Cl and =CH groups affords metalladiynes such as frans-W C=C(tol) (=CC6H4C=CSiPr 3)... 

Some of these intermediates are analogous to those proposed by Chauvin in olefin metathesis ( Chauvin s mechanism ) [36]. They can be transformed into new olefins and new carbene-hydrides. The subsequent step of the catalytic cycle is then hydride reinsertion into the carbene as well as olefin hydrogenation. The final alkane liberation proceeds via a cleavage of the Ta-alkyl compounds by hydrogen, a process already observed in the hydrogenolysis [10] or possibly via a displacement by the entering alkane by o-bond metathesis [11]. Notably, the catalyst has a triple functionality (i) C-H bond activation to produce a metallo-carbene and an olefin, (ii) olefin metathesis and (iii) hydrogenolysis of the metal-alkyl. 

Ring-closing metathesis of an enyne, which has double and triple bonds in the molecule, is a remarkable reaction which is useful in synthetic organic chemistry. In enyne metathesis, the double bond is cleaved and carbon-carbon bond formation occurs between the double and triple bonds. The cleaved alkylidene part is moved to the alkyne carbon. Thus, the cyclized compound formed in this reaction has a diene moiety [Eq. (6.77)]. The reaction is also called skeletal rearrangement and is induced by Pt, Pd, Ga, and Ru catalysts ... 

In alkyne metathesis, the triple bond of an alkyne is cleaved and triple-bond con-... 

The polymerization of the alkyne triple bond (Secs. 5-7d and 8-6c) and ring-opening metathesis polymerization of a cycloalkene (Secs. 7-8 and 8-6a) yield polymers containing double bonds in the polymer chain. Cis-trans isomerism is possible analogous to the 1,4-polymer-ization of 1,3-dienes. 

New applications continue to demonstrate the enormous versatility of RCM for organic synthesis. Examples include triple ring closing (Eq. 48) and alkyne metathesis, an example being that of cross-metathesis that provides an efficient synthetic strategy for prostaglandin E2 (Eq. 49). Amines and alcohols deactivate metathesis catalysts, but their protection as ethers, esters, and amides allows them to be incorporated into the designated transformation. 

Alkyne metathesis is a curious reaction in view of the fact that two alkyne triple bonds are cleaved and reconstructed simultaneously leading to different triple bonds. The first reported effective catalyst is a heterogeneous mixture of tungsten oxide and silica. Then Mortreux found that a catalytic system that consisted of Mo(CO)6 and resorcinol was effective for alkyne metathesis. As reported, the added alkynes come into equilibrium with different product... 

A novel complex, Mo[N( Bu) (Ar)]3 140, was prepared and shown to activate the triple bond in molecular nitrogen in a stoichiometric fashion. However, the complex, when used for alkyne metathesis, does not affect the expected transformation, but undergoes a vigorous endothermic process in a CH2CI2 solution. The resultant solution... 

Experimental observations with the Ti(0- -Bu)4 + Et3Al catalyst support the insertion mechanism versus metathesis polymerization.412 Propagation occurs via the cis opening of the triple bond of the coordinated monomer, leading to addition to the Ti—C bond between the growing polymer chain and the catalyst center ... 

The chemistry of CR fragments ligating metal centers has been a topic of considerable interest since the discovery of the first alkylidyne-metal complexes in E.O. Fischer s Laboratory in 1973 (1). These ligands have been implicated in Fischer-Tropsch reactions (2) and in alkyne metathesis (5). Moreover, the isolation of stable compounds containing carbon-metal triple bonds completed the matrix of bond types represented here ... 

SCHEME 1. Types of alkene and alkyne metathesis reactions. DBC, double bond cleavage TBC, triple bond cleavage ADMET, acyclic diene metathesis RCM ring-closing metathesis ROMP ring-opening metathesis polymerization... 

The metathesis polymerization of diynes having four single bonds between the triple bonds (dipropargyl compounds) yields cyclopolymers. The structural units may contain a cyclohexene ring (equation 63) or a cyclopentene ring (equation 64) with the possibility... 

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],... 

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