Metathesis, Alkyne

Ring-Closing Alkyne Metathesis (RCAM) and Alkyne... 

Fig. 3a,b Typical diyne metathesis reactions ring-closing alkyne metathesis (RCAM, a) diyne cross metathesis (ACM, b)... 

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. 

Thus far, chemists have been able to influence the stereoselectivity of macro-cyclic RCM through steric and electronic substrate features or by the choice of a catalyst with appropriate activity, but there still exists a lack of prediction over the stereochemistry of macrocyclic RCM. One of the most important extensions of the original metathesis reaction for the synthesis of stereochemi-cally defined (cyclo)alkenes is alkyne metathesis, followed by selective partial hydrogenation. 

Lindel T (2003) Alkyne metathesis in natural product synthesis. In Schmalz HG, Wirth T (eds) Organic synthesis highlights, vol V. Wiley-VCH, Weinheim, p 27... 

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]. 

An interesting series of ring-closing alkyne metathesis reactions (RCAM) has recently been reported by Fiirstner and coworkers (Scheme 6.72) [152], Treatment of biaryl-derived diynes with 10 mol% of a catalyst prepared in situ from molybdenum hexacarbonyl and 4-(trifluoromethyl)phenol at 150 °C for 5 min led to a ca. 70% iso-... 

Scheme 6.72 Ring-closing alkyne metathesis reactions.

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... 

Intermolecular-enyne metathesis, if it is possible, is very unique because the double bond of the alkene is cleaved and each alkylidene part is then introduced onto each alkyne carbon, respectively, as shown in Scheme 9. If metathesis is carried out between alkene and alkyne, many olefins, dienes and polymers would be produced, because intermolecular enyne metathesis includes alkene metathesis, alkyne metathesis and enyne metathesis. The reaction course for intermolecular enyne metathesis between a symmetrical alkyne and an unsym-metrical alkene is shown in Scheme 9. The reaction course is very complicated, and it seems impossible to develop this reaction in synthetic organic chemistry. 

G. Brizius, N.G. Pschirer, W. Steffen, K. Stitzer, H.-C. zur Loye, and U.H.F. Bunz, Alkyne metathesis with simple catalyst systems efficient synthesis of conjugated polymers containing vinyl groups in main side chain, J. Am. Chem. Soc., 122 12435-12440, 2000. 

N.G. Pschirer and U.H.F. Bunz, Poly(fluorenylene ethynylene)s by alkyne metathesis optical properties and aggregation behavior, Macromolecules, 33 3961-3963, 2000. 

Ethylene-alkyne metathesis, 26 955-956 Ethylene-a-olefin copolymers,... 

The chemistry of alkylidene and alkylidyne complexes of early transition metals was developed by Schrock and co-workers and these complexes turned out to be of crucial importance to alkene and alkyne metathesis. Initially their research focused on tantalum complexes of the type CpTaCEIE, which after a-elimination (Figure 16.6) led to alkylidene complexes Cp(R)Cl2Ta=CHR [11]. 

This review deals with the synthesis of PAEs. Described are the developments this field has undergone in the last 4 years. A comprehensive review on PAEs appeared in 2000 (Table 1, entry 1) [Ij. Several other noteworthy PAE reviews are those of Yamamoto (Table 1, entries 7,8) that cover mostly heterocyclic representatives and Pinto and Schanze s review (Table 1, entry 6) about water-soluble conjugated polymers. The specific area of dialkyl PPEs and their synthesis by alkyne metathesis has been reviewed recently (Table 1, entries 2-4)... 

Bunz UHF (2001) Acc. Chem. Res. 34 998-1010 Poly(p-phenyleneethynylene)s by alkyne metathesis... 

In Table 8 all-hydrocarbon PAE backbones are shown, while in Table 9 PAEs with heterocyclic backbones are fisted. Alkyne metathesis is a powerful tool to make poly(fluorenyleneethynylene)s (PFEs, Table 8, entries 1-7). The... 

Regardless of whether the Pd-catalyzed coupling or alkyne metathesis is utilized to make PAEs, the critical step is the synthesis of the diiodoarene monomers. In this section some of the more interesting syntheses are showcased. The synthesis of dipropynyldi-tert-butylnaphthalene is shown in Scheme 5. Starting from naphthalene, Friedel-Crafts alkylation with 2-chloro-2-methylbutane gives a mixture of two di-tert-butylnaphthalenes that are separated by crystallization. Iodination of the correct isomer is followed by a Pd-catalyzed coupling of propyne to the diiodide to give the desired l,5-dipropynyl-3,8-di-tert-butyl-naphthalene [56] ready for ADIMET. 

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