Cyclization reactions metathesis

Cycloisomerization of dienes and enynes into cyclic molecules with Grubbs second-generation catalysts modified by reaction with DMF has been reported to give a species able to catalyse the cyclization reaction.Metathesis of a bicyclic diene in the presence of ethane has been reported to give di-fused[3.0.3]carbocycles via a ring-rearrangement metathesis transformation (Scheme 95). " ... 

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]. 

Enyne metathesis is unique and interesting in synthetic organic chemistry. Since it is difficult to control intermolecular enyne metathesis, this reaction is used as intramolecular enyne metathesis. There are two types of enyne metathesis one is caused by [2+2] cycloaddition of a multiple bond and transition metal carbene complex, and the other is an oxidative cyclization reaction caused by low-valent transition metals. In these cases, the alkyli-dene part migrates from alkene to alkyne carbon. Thus, this reaction is called an alkylidene migration reaction or a skeletal reorganization reaction. Many cyclized products having a diene moiety were obtained using intramolecular enyne metathesis. Very recently, intermolecular enyne metathesis has been developed between alkyne and ethylene as novel diene synthesis. 

In addition to reactions characteristic of carbonyl compounds, Fischer-type carbene complexes undergo a series of transformations which are unique to this class of compounds. These include olefin metathesis [206,265-267] (for the use as metathesis catalysts, see Section 3.2.5.3), alkyne insertion, benzannulation and other types of cyclization reaction. Generally, in most of these reactions electron-rich substrates (e.g. ynamines, enol ethers) react more readily than electron-poor compounds. Because many preparations with this type of complex take place under mild conditions, Fischer-type carbene complexes are being increasingly used for the synthesis [268-272] and modification [103,140,148,273] of sensitive natural products. 

With the ready availability of 2-fluoro-allylic halides and a-fluoroacrylic acid derivatives, incorporation of a pendant fluorovinyl unit is easier than ever. The utility of these products is markedly enhanced by the reactivity of the fluorovinyl unit in olefin metathesis reactions. Some success has been found in cyclization reactions as shown below [83] (Scheme 36). 

A novel approach to enantiopure spirocyclic (3-lactams has been developed by Alcaide et al. [106] using different intramolecular metal catalyzed cyclization reactions with monocyclic unsaturated alcohols 142 (Scheme 35). Ring-closing metathesis is one of the most powerful and reliable methods to construct a ring system. Transformation of alcohols in diolefin precursors followed by ring-closing... 

Olefin metathesis does not generate stereogenic centers, however, the reaction may be employed in the desymmetrization of prochiral (poly)olefins of the kinetic resolution of racemates. In the example depicted in Scheme 17, a trialkene is desymmetrized, and the preference for the cyclization reaction with one of the two symmetry-equivalent C = C double bonds leads to the enantioselective formation of the reaction product, a chiral dihydrofuran. The following principal conclusions can be drawn from this study ... 

Asymmetric syntheses of natural products cyclization reactions using molybdenum and tungsten imido alkylidene complexes as efficient olefin-metathesis catalysts 03AG(E)4592. 

The polymerization of ether and thioether monomers was also studied, and it was found that the rate of polymerization was a great deal slower with the functionalized monomers. The number of methylene units between the olefin and the heteroatom greatly affected the rates observed, giving credence to the chelation effect shown in Fig. 6.1. In addition, catalyst 2 polymerizes 1,5-hexadiene, whereas catalyst 6 mainly cyclizes the metathesis dimer to cyclo-l,5-octadiene. At this point there is no clear explanation for this result, and, furthermore, the reason that the COD generated did not undergo ROMP in these reactions is unclear. The data from these experiments clearly shows that Lewis basic functionality retards the rate of metathesis with complex 6 more than with complex 2, although 6 is clearly the more functional group-tolerant complex overall [35]. 

Cossy et al. demonstrated that, in the presence of the ruthenium catalyst 10 and Pt02, the tandem cross-metathesis—hydrogenation—cyclization reactions of the alkenol 19 with acrylic acid 20 or acrolein 21 under H2 atmosphere gave the lactone 22 or lactol 23, respectively (Scheme 8).89 The ruthenium catalyst 10 and Pt02 are compatible under the reaction conditions. 

In some palladium-catalyzed cyclizations of enynes a [2 + 2] cycloaddition with subsequent metathesis-like rearrangement leads to other cyclic products50,51. The transition metal catalyzed Alder ene type cyclization reactions can also be applied to diynes52 and to enal-lenes53-55. The latter reaction is best performed using a polystyrene-supported nickel(II)/ chromium(II) catalyst. With the appropriate choice of substituents complete stereoselectivity can be achieved using this method55. 

Only two syntheses of the complete ring structure system present in 1 have been achieved. In 1996 Pandit s group reported the total synthesis of the ABCDE core with the correct stereochemistry at the chiral carbon-centers. Key steps in the synthetic route were the formation of both the eight- and the 13-membered rings by the aforementioned metathesis cyclization reaction [94] (see Scheme 31). 

To complete this short treatment on solid-phase synthesis, let us be mention the efforts made by several groups to obtain methods that allow a cyclorelease (also called cyclative cleavage) of the macrocycle, in other words, the cyclization reaction and the release from the polymer support occur simultaneously. The methods developed so far involve the metathesis reaction (Fig. 15a) the Stille coupling (Fig. ISb) and sulfur ylides (Fig. 16a). 

This was utilized to form several novel homopolymers with l,2-bis(3-thienyl)cyclopentene derivatives using ring-opening metathesis polymerization techniques. The color forming cyclization reaction in the polymers can be illustrated as follow ... 

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