Alkyne metathesis reaction complexes

This mechanism was later confirmed experimentally in 1981 by Schrock and others, who reported the first example of alkyne metathesis by tungsten(vi)-alkylidyne complex. They have prepared tungsten alkylidyne complex 120 (Equation (21)) and found that it reacts with diphenylacetylende to give tungsten alkylidyne complex 121 and another alkyne 122 (lequiv.) (Equation (22)). Furthermore, complex 121 works as a catalyst for the alkyne metathesis reaction. 

The organic reactivity of the alkylidyne complexes has been extensively studied especially with regard to alkene and alkyne metathesis reactions.353,356... 

Storm, C., and Madsen, R. 2003. Enyne metathesis catalyzed by ruthenium carbene complexes (review of alkyne metathesis reactions). Synthesis 1—19. 

Addition of pyridine and acetylene results in generation and trapping of the complex shown in equation (87), which has a reduced bond order. In this complex, the acetylene bridges the two metals. This type of chemistry was initially developed by Schrock and coworkers for alkyne metathesis (see Alkyne Metathesis) reactions but has been subsequently developed by a number of other researchers. 

Perhaps the most remarkable illustration of the ability of metals to activate alkynes comes from reactions in which complete scission of the carbon-carbon triple bond occurs. On the stoichiometric level these include examples in which carbyne complexes are produced from alkyne completes as in the melt-thermolysis of CpCo(PPh3)(RCsCR) [112] or from reactions of alkynes with unsaturated metal species (Scheme 4-34) [113]. The remarkable alkyne metathesis reaction (Scheme 4-35), which involves overall cleavage and regeneration of two o-and four rt-bonds, is conceptually related. A variety of functionalized alkynes can be tolerated as metathesis substrates [114] and especially effective catalysts for these reactions are Mo(VI)-and W(VI)-carbyne complexes. Metallacyclobutadienes 64, formed by the reaction of the alkyne with a metal-carbyne complex, appear to be central intermediates in these reactions and the equilibrium between metallacycle and alkyne/metal-carbyne is observable in some cases [115]. 

A number of authors have reported successful alkyne metathesis reactions catalysed by either tungsten " molybdenum" complexes. 

Olefin metathesis reactions cleave carbon-carbon double bonds and reassemble tiiem to generate products containing new carbon-carbon double bonds. This process requires a catalyst and is largely controlled by thermodynamics (Equation 21.1). Alkyne metathesis reactions cleave carbon-carbon triple bonds and reassemble them to form products containing new carbon-carbon triple bonds (Equation 21.2). The observation of complete cleavage of strong carbon-carbon multiple bonds by a catalytic process was remarkable when first discovered, but many transition metal complexes are now known that catalyze these reactions with fast rates. One might expect that the equilibrium control of this reaction would limit its use, but olefin metathesis has become one of the most useful reactions catalyzed by transition metal complexes. 

Metallabenzenes have been invoked as possible intermediates in several other reaction types. Schrock, " for example, proposed tungstenabenzenes as possible intermediates in certain alkyne metathesis reactions that proceed by associative mechanisms. Shown in Scheme 32 is a proposed sequence for the metathesis of 3-heptyne to 3-hejQTie and 4-octyne using a tungstenacyclobutadiene complex as catalyst. The postulated metallabenzenes are formed by alkyne insertion into the metal carbon bonds of the metallacyclobutadienes. Of course, it is also possible to envisage a catalytic cycle based on Dewar metallabenzene intermediates. 

Katz and coworkers [73] proposed the currently accepted mechanism for the alkyne metathesis reaction (Scheme 6.18b). In their proposal, the incoming alkyne reacts with a metal alkylidyne complex (56), generating a metallacyclobutadiene intermediate (57) that generates the expected products and a new alkylidyne species (58) through cycloreversion. The reaction of a second alkyne with the... 

Computational studies on the alkyne metathesis reaction have focused mainly on well-defined d°-alkylidyne complexes as the catalyst precursors [77, 78, 85, 87-89]. The early work on the non-catalytically active W(=CfBu)Cl3 complex... 

Metathesis reactions are very powerful tools to create C—C bonds and provide synthetic chemists with synthetic design based on an unprecedented retrosynthetic analysis of complex compounds in very elegant and efficient ways. As the impact of metathesis in modern synthetic chemistry of drug and natural product is evidenced by a number of publications and reviews, in this chapter, we describe the most illustrative strategies of metathesis and their applications to drug and natural product syntheses in line with types of olefin, enyne, and alkyne metathesis reactions. 

Hexacarbonyldicobalt complexes of alkynes have served as substrates in a variety of olefin metathesis reactions. There are several reasons for complex-ing an alkyne functionality prior to the metathesis step [ 125] (a) the alkyne may chelate the ruthenium center, leading to inhibition of the catalytically active species [125d] (b) the alkyne may participate in the metathesis reaction, giving undesired enyne metathesis products [125f] (c) the linear structure of the alkyne may prevent cyclization reactions due to steric reasons [125a-d] and (d) the hexacarbonylcobalt moiety can be used for further transformations [125c,f]. 

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. 

Aside from the Ziegler-Natta polymerization, alkene and alkyne metathesis, and other reactions of Ti-methylene complexes, carbometallation reactions induced by alkyltitanium compounds have been dominated by those involving... 

Although the transformation of a primary alkyne into a vinylidene complex, 2, in presence of a number of transition metal systems is well reported [2, 3], only rare examples are known for the transformation of an alkene into a carbene complex [4, 5]. Given the increased role played by vinylidene and carbene complexes as key partners in metathesis reactions and related catalytic processes [6, 7], opening up new efficient and easy synthetic routes to such complexes is an important challenge. 

At the same time, Filrstner used tungsten alkyUdene complex 150 developed by Schrock for ring-closing alkyne metathesis. He compared the reactivities of tungsten alkylidyne complex 150 and Mo(CO)6-p-ClC6H40H (Table 6.4) and showed that both catalysts work well, although a higher reaction temperature is required in the case of Mo(CO)6-p-chlorophenol. 

Another focus of this chapter is the alkynol cycloisomerization mediated by Group 6 metal complexes. Experimental and theoretical studies showed that both exo- and endo- cycloisomerization are feasible. The cycloisomerization involves not only alkyne-to-vinylidene tautomerization but alo proton transfer steps. Therefore, the theoretical studies demonstrated that the solvent effect played a crucial role in determining the regioselectivity of cycloisomerization products. [2 + 2] cycloaddition of the metal vinylidene C=C bond in a ruthenium complex with the C=C bond of a vinyl group, together with the implication in metathesis reactions, was discussed. In addition, [2 + 2] cycloaddition of titanocene vinylidene with different unsaturated molecules was also briefly discussed. 

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