Applications of Alkyne Metathesis

This short review focuses on the application of alkyne metathesis in the field of natural product synthesis, which is central for the evaluation and ranking of synthetic methods. Natural products are often complex, with the simultaneous presence of different functional groups and novel molecular architecture. If a method works for chemicals bought from the... 

With the discovery by Grubbs of ruthenium carbene complexes such as Cl2(PCy3)2Ru=CHR, which mediate olefin metathesis under mild reaction conditions and which are compatible with a broad range of functional groups [111], the application of olefin metathesis to solid-phase synthesis became a realistic approach for the preparation of alkenes. Both ring-closing metathesis and cross-metathesis of alkenes and alkynes bound to insoluble supports have been realized (Figure 5.12). 

The use of alkyne metathesis in organic synthesis is not as extensive as alkene metathesis. Nevertheless, there are some interesting applications that have been reported over the past decade. We will briefly consider a couple of these here. 

Although alkyne metathesis has been used in polymerization reactions, these applications are not nearly as well advanced as those involving ROMP or ADMET polymerization of alkenes. Further discussion of alkyne metathesis polymerizations is beyond the scope of this text. 

The most recent application of olefin metathesis to the synthesis of polyenes has been described by Tao and Wagener [105,117], They use a molybdenum alkylidene catalyst to carry out acyclic diene metathesis (ADMET) (Fig. 10-20) on either 2,4-hexadiene or 2,4,6-octatriene. The Wagener group had earlier demonstrated that, for a number of nonconjugated dienes [118-120], these polymerizations can be driven to high polymer by removal of the volatile product (e. g., 2-butene). To date, insolubility limits the extent of polymerization of unsaturated monomers to polyenes containing 10 to 20 double bonds. However, this route has some potential for the synthesis of new substituted polyacetylenes. Since most of the monomer unit is preformed before polymerization, it is possible that substitution patterns which cannot be incorporated into an alkyne or a cyclic olefin can be built into an ADMET monomer. 

Technology for a number of applications of olefin metathesis has been developed (, fO At Phillips, potential processes for producing isoamylenes for polyisoprene synthesis and long-chain linear olefins from propylene have been through pilot plant development. In the area of specialty petrochemicals, potential industrial applications include the preparation of numerous olefins and diolefins. High selectivities can be achieved by selection of catalyst and process conditions. The development of new classes of catalysts allows the metathesis of certain functional olefins (, 14). The metathesis of alkynes is also feasible (15) ... 

Metallacyclobutanes or other four-membered metallacycles can serve as precursors of certain types of carbene complex. [2 + 2] Cycloreversion can be induced thermally, chemically, or photochemically [49,591-595]. The most important application of this process is carbene-complex-catalyzed olefin metathesis. This reaction consists in reversible [2 + 2] cycloadditions of an alkene or an alkyne to a carbene complex, forming an intermediate metallacyclobutane. This process is discussed more thoroughly in Section 3.2.5. 

The heterocyclic PAEs are useful for low-bandgap applications, as n-type semiconductors, and in sensory applications. Again, as long as the alkynylated or iodinated monomers are available, the synthesis of the corresponding PAE is not a problem, and either the Pd-catalyzed couplings or alkyne metathesis can be utilized toward that end. 

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. 

Metathesis of alkynes is a much less general reaction and has not yet found the attention that alkene metathesis has received.158-160 Nonetheless, a few observations have shown that it has the potential of useful applications emerging as a new synthetic tool.214-216... 

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-... 

In yet another successful application of the traditional Noyori three-component reaction, Ftirstner and co-workers took advantage of their remarkable alkyne metathesis reaction [21] to synthesize therapeutically promising cyclic analogues of prostaglandins [22] such as PGE2-l-15-lactone 34 (Figure 12.1) [23]. 

The application of alkene [1] - and, more recently, enyne [2] and alkyne - metathesis to the synthesis of natural products has been triggered by the development of powerful catalysts that allow metathesis reactions to be carried out under mild conditions. Scheme 1 outlines two important cases of alkene and alkyne metathesis of particular interest to the synthesis of natural products (together with the general scheme of enyne metathesis, not discussed in this review). The metathesis products can be obtained in high yields, since ethene/2-butyne are formed as volatile products. After the alkene/alkyne metathesis, the substituents (R) of the alkenes/alkynes are located on the same multiple bond. Enyne metathesis can be considered as the more general case of alkene metathesis, because two new double bonds are again formed, albeit now connected by a single bond. 

Scheme 5. Combined application of alkene and alkyne metathesis, affording the open-chain natural product 24.

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]. 

Metathesis is a versatile reaction applicable to almost any olefinic substrate internal, terminal or cyclic alkenes, as well as dienes or polyenes. (Alkyne metathesis is a growing area, but will not be dealt with here.) The reaction is also known as olefin disproportionation or olefin transmutation, and involves the exchange of fragments between two double bonds. Cross metathesis (CM, Figure 1) is defined as the reaction of two discrete alkene molecules to form two new alkenes. Where the two starting alkene molecules are the same it is called self-metathesis. Ethenolysis is a specific type of cross metathesis where ethylene... 

Schrock RR, Czekelius C. Recent advances in the syntheses 136. and applications of molybdenum and tungsten alkylidene and alkylidyne catalysts for the metathesis of alkenes and alkynes. 

Among the polymers containing aromatic rings and unsaturated hydrocarbon groups in the backbone are poly(phenylene-ethynylenes) (PPE). This type of polymer has been synthesized by alkyne metathesis of 1,4-dipropynylated benzenes [11] and has applications in optical and electronic industry. A comprehensive study on thermal decomposition of several poly(substituted p-phenylene-ethynylenes) is available [12], The general formula for this group of polymers is the following ... 

Furstner, A., Guth, O., Rumbo, A., Seidel, G. Ring Closing Alkyne Metathesis. Comparative Investigation of Two Different Catalyst Systems and Application to the Stereoselective Synthesis of Olfactory Lactones, Azamacrolides, and the Macrocyclic Perimeter of the Marine Alkaloid Nakadomarin A. J. Am. Chem. Soc. 1999,121,11108-11113. 

Furstner, A., Grela, K. Ring-closing alkyne metathesis application to the stereoselective total synthesis of prostaglandin E2-1,15-lactone. Angew. Chem., Int. Ed. Engl. 2000, 39, 1234-1236. 

Furstner, A., Radkowski, K., Grabowski, J., Wirtz, C., Mynott, R. Ring-Closing Alkyne Metathesis. Application to the Total Synthesis of Sophorolipid Lactone. J. Org. Chem. 2000, 65, 8758-8762. 

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