Alkyne metathesis examples

The second example involves the synthesis of ortho-dipropynylated arenes (Scheme 4.12b), which serve as precursors to tribenzocyclyne by way of an alkyne metathesis reaction (see also Scheme 6.31). Here, a Sonogashira reaction was carried out in a pre-pressurized (propyne at ca. 2.5 bar) sealed microwave vessel in a standard single-mode microwave reactor. Double-Sonogashira coupling of the dibromodiiodo-benzene was completed within 20 min at 110 °C [30]. 

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. 

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. 

RCM of dienes to cycloalkenes provides a useful method for the syntheses of carbo- and heterocycles and thus has been proved to be extremely effective in total synthesis of various natural products. Usually, however, mixtures of (E)- and (Z)-olefms result. In contrast, ring-closing alkyne metathesis provides a reliable route for synthesis of both (E)- and (Z)-macrocycloalkenes in a stereoslective manner taking advantage of stereoselective partial reduction of resulting cycloalkynes. A Lindlar reduction gives (Z)-cycloalkenes, whereas a hydroboration/ protonation sequence afford ( )-cycloalkenes (Equation (23)). Recently, Trost reported an alternative procedure for the synthesis of (E)-olefins from alkynes through hydrosilylation by a ruthenium catalyst. This procedure converts cycloalkyne 130, for example, to vinylsilane 131 and then to (E)-cycloalkene 132 in a stereoselective manner (Scheme 46)7 ... 

Mark Overhand of Leiden University recently reported (Tetrahedron Lett. 2004,45,4379) an example of alkyne-alkyne metathesis, the cyclization of 17 to 19. For this reaction, a tungsten catalyst was used. 

A particularly interesting example is the synthesis of alkyne-bridged oligomers and polymers, which are attractive materials for optical and electronic applications. Bunz and coworkers were able to modify the Mortreux catalyst system [Mo(CO)6 and a suitable phenol]11 and reaction conditions to perform acyclic alkyne metathesis of 1,4-dipropynylated benzenes to produce high-molecular-weight poly(p-... 

Scheme 3. Simple examples of natural products synthesis by alkyne metathesis with the Mortreux catalyst.

The most recent method developed for the nA —> An approach relies on dynamic covalent bond formation using a metathesis reaction. In this case, reactions are typically under thermodynamic control, providing the potential for increased selectivity in product formation. The initial examples using alkyne metathesis toward the formation of SPMs were reported by Adams, Bunz, and coworkers using the precatalyst [Mo(CO)6] [27,28], but rather low yields of the desired products (4) limited general applicability (Scheme 6.2). Recent efforts by Moore and coworkers using a Mo(VI)-alkylidyne catalyst, however, have refined this process such that precipitation-driven reactions now provide moderate to excellent results (see Scheme 6.24) [29]. 

Alkynes enter into many cycloaddition reactions and by analogy so do some alkylidyne complexes. Selected examples are shown in Figure 5.43 however, those involving alkynes are reserved for discussion in the following section (alkyne metathesis). 

It is perhaps premature to attempt to delineate the factors that determine whether symmetrical or distorted metallacyclobutadiene or t 3-cycopropenyl coordination is observed, given the comparitive sparsity of directly comparable examples, and the observation that tautomerism appears to operate between coordination modes in some cases. A similar situation arises for cyclobutadiene coordination vs. metallacyclopentadi-ene formation (Figures 6.38, 6.39, 7.19). In both cases the metallacycles are important intermediates in catalytic manifolds (alkyne metathesis and oligomerization, respectively) and in both cases the polyhapto variant represents a tangent to the productive catalytic cycle, formation of which may be reversible or in some cases may lead to termination. 

Like their metal acycloalkane analogs, the chemical behavior of the unsaturated species is quite different from the corresponding heterocycles without a metal atom. Metallacycloalkenes appear also as reactive intermediates, e.g., in alkyne trimerization or cotrimerization with heterosystems or in alkyne metathesis. Some important examples are given in the following sections. 

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]. 

Alkyne metathesis is generally restricted to internal alkynes, and is driven to completion by the evolution of gaseous 2-butyne. Representative examples of alkyne cross-metathesis are depicted in Scheme 33, and include (i) dimerization of alkynylbenzoic acid derivative 287, (ii) alkyne cross-metathesis of 289 and bis(trimethylsilyl)acetylene, (iii) cross-metathesis of enyne 291 and various alkynes and metathesis dimerization of 291, and (iv) formation of high molecular weight alkyne-containing polymers through acyclic diyne metathesis (ADIMET) polymerization of acyclic diynes (e.g., 293) " using the molybdenum hexacarbonyl/2-chlorophe-nol system. 

In Section 24.12, we introduced alkene (olefin) metathesis, i.e. metal-catalysed reactions in which C=C bonds are redistributed. The importance of alkene and alkyne metathesis was recognized by the award of the 2005 Nobel Prize in Chemistry to Yves Chauvin, Robert H. Grubbs and Richard R. Schrock for the development of the metathesis method in organic synthesis . Examples of alkene metathesis are shown in Figure 27.3. The Chauvin mechanism for metal-catalysed alkene metathesis involves a metal alkyli-dene species and a series of [2 + 2]-cycloadditions and cycloreversions (Figure 27.4). Scheme 27.6 shows the mechanism for alkyne metathesis which involves a high oxidation state metal alkylidyne complex, L M=CR. 

Naturally, the question arises What accounts for the dramatic difference in yields between these processes Macrocyclization under kinetic control, as shown by the Staab example, is clearly not a favorable situation, as evidenced by the low yield of 14a. In contrast, it has been shown that when alkyne metathesis macrocyclization is under thermodynamic control, [n]cycles are the lowest-energy product [64]. ADIMAC of monomer 15a under the conditions shown in Scheme 6.8 generate [6]cycle 16 as the major product, and [5]cycle 17 as a minor product. Gel permeation chromatography (GPC) analysis confirmed that the oligomeric products (both linear and cyclic) that are initially formed in the reaction are consumed over time, and the [5-6]cycles are the major product upon completion. More dramatically, when polymer 15b was subjected to the same conditions, the major products... 

More extensive use of alkyne metathesis in materials synthesis has exploited addition metathesis processes. Several examples of addition metathesis reactions are shown in Equations 21.33-21.36. In Equations 21.33-21.35, dimethylacetylenes undergo alkyne metathesis in the presence of Schrock s alkylidyne catalyst to generate butyne and the polymeric... 

The use of alkyne cross metathesis for the synthesis of unsymmetrical alkynes has potential utility in synthesis, although it has been studied less intensively than alkene cross metathesis. Mori published some of the first examples of alkyne cross metathesis to generate unsymmetrical alkynes. One example of this reaction conducted with the Montreux-type catalyst is shown in Equation 21.37. The selectivity for the cross-metathesis product was achieved by the use of an excess of the diphenylacetylene. A second example was conducted with the catalyst generated from Cummins trisamido complex. As shown in Equation 21.38, this cross metathesis was conducted in acceptable yields... 

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. 

This chapter is arranged by the well-recognized types of olefin metathesis reactions, that is, ring-opening metathesis polymerization (ROMP), acyclic diene metathesis (ADMET) polymerization, ring-closing metathesis (RCM), and crossmetathesis (CM) (Fig. 12.1). Examples of alkyne metathesis are also included. 

---