Tungsten catalysts alkyne metathesis

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. 

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. 

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... 

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. 

Although the real species of this solution for alkyne metathesis is not clear, this complex is an excellent tool from a preparative point of view. It is very active for the formation of cycloalkynes of different ring sizes from diynes. In contrast to tungsten alkylidyne complex 1, catalyst I4O/CH2CI2 is sensitive toward acidic protons such as amide proton and exhibited remarkable tolerance toward many polar functional groups (Table 6). ... 

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. 

In the early 1980s, Schrock prepared a series of tungsten- and molybdenum-based carbyne complexes, and demonstrated that they are viable catalysts for performing stoichiometric and catalytic alkyne metathesis [7]. With the defined carbyne complexes, he laid the foundation for the mechanistic understanding of alkyne metathesis, and was the first to demonstrate that vinyl-substituted carbyne complexes are stable [8] and that alkyne metathesis could be performed in the presence of C=C double bonds. 

It is important to note that this reaction works only with W2(OCMe3)6 and not with any other M2(OR)6 molecule and that while it appears to be general for aliphatic R it does not proceed for R = QH5. It goes under very mild conditions and is virtually quantitative. Since the (Me3CO)3W=CR compounds are alkyne metathesis catalysts, still other tungsten alkylidyne compounds, not obtainable in the above reaction, can be obtained by the following reaction ... 

Ring-closing metathesis is not limited to olefins. Catalysts promoting ring closure of alkynes [20] have also been developed (Scheme 9). Alkyne 56 can easily be converted into cyclic alkyne 57 with a yield of 73 %. For this purpose, a tungsten catalyst has been used. 

Metallacyclobutadienes are known to be intermediates in alkyne metathesis (Scheme Preferred metathesis catalysts are tungsten com-... 

The general equation and mechanism for alkyne metathesis is depicted in Scheme 31. Alkyne metathesis is considerably less well developed in comparison to alkene metathesis. Garbyne complexes or carbyne complex precursors are among the most effective alkyne metathesis catalysts representative catalysts are depicted in Scheme 32. Tungsten carbyne complex 276 is one of the earliest alkyne metathesis catalysts, and has frequently been employed to initiate... 

Alkyne metathesis, using either preformed carbyne complexes, or carbyne complexes generated in situ, has started to find use in recent years, particularly as more reactive catalysts have been developed. The introduction of stable carbyne complexes, such as tungsten complex 8.483, as more-active catalysts started to make the reaction practicable for organic synthesis. ... 

Alkynes can also undergo metathesis. The preferred catalysts for alkyne metathesis are Schrock catalysts—catalysts that contain molybdenum or tungsten as the transition metal. 

Synthesis of Schrock s W tungsten-carbyne complex, the prototype of active alkyne metathesis catalysts... 

Cruentaren A 3 has two Z alkenes, so the authors chose a bis-alkyne strategy, with a partial hydrogenation of both alkynes at the end of the synthesis. To this end, alkyne metathesis was accomplished with the Schrock tungsten carbine catalyst 13. Homologation to 15 followed by deprotection and hydrogenation then gave enantiomerically pure cruentaren A3. 

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