Carbenes ring-closing metathesis

Keywords Ruthenium-carbenes, Ruthenium-allenylidenes, Ring closing metathesis, Natural product synthesis, Fine chemicals. 

Closely related to the ring-closing metathesis of enynes (Section 3.2.5.6), catalyzed by non-heteroatom-substituted carbene complexes, is the reaction of stoichiometric amounts of Fischer-type carbene complexes with enynes [266,308 -315] (for catalytic reactions, see [316]). In this reaction [2 + 2] cycloaddition of the carbene complex and the alkyne followed by [2 -t- 2] cycloreversion leads to the intermediate formation of a non-heteroatom-substituted, electrophilic carbene complex. This intermediate, unlike the corresponding nucleophilic carbene... 

Synthetic Applications of Non-Heteroatom-Substituted Carbene Complexes Table 3.18. Formation of cycloalkenes by ring-closing metathesis. 

Homogeneous Catalysis through Heterogeneous Ru Carbenes 471 Tab. 11.1 Ring-closing metathesis of acyclic dienes by Ru complex (10). ... 

Triene 257 was transformed into the racemic cyclopentenone 258 by a ring closing metathesis using Grubbs iST-heterocyclic carbene catalyst (102) [55]. 

The Tins group used Grubbs AT-heterocyclic carbene catalyst (102) for the ring closing metathesis of the triene 262 (Eq. 4) [55, 133] ... 

Murakami et al. reported a ring-closing metathesis reaction of allenynes using Schrock s molybdenum alkylidene complex [37]. Treatment of allenynes ISl with a catalytic amount of the complex 15 2 in toluene at rt gave cyclopentene derivatives 1 S3 in good yield. Two possible reaction mechanisms were proposed, one through a vinylidene complex 154 and the other through a carbene complex, but based on several mechanistic studies, they favored the vinylidene complex pathway, which is shown here (Scheme 5.42). 

Catalytic processes using diazo chemistry and stoichiometric methods with Fischer carbenes are complimentary for the introduction of a substituted carbene into a molecule. For methylene addition, however, there is no viable alternative to the modified Simmons-Smith reaction. Ring-closing metathesis, and its ROMP counterpart, have matured so fast that even now they rank among the most useful synthetic methodologies in organic chemistry. 

Several examples of ring-closing metathesis indicate the highly selective nature of this reaction.161,162,224-226 The application of various Mo and Ru carbene catalysts allow formation of five-, six-, and seven-membered mono- and bicyclic rings. Formation of substituted cyclopentenes, for example, was shown... 

For the cleavage of alkenes from a support by metathesis, several strategies can be envisaged. In most of the examples reported to date, ring-closing metathesis of resin-bound dienes has been used to release either a cycloalkene or an acyclic alkene into solution (Figure 3.38, Table 3.44). Further metathesis of the products in solution occurs only to a small extent when the initially released products are internal alkenes, because these normally react more slowly with the catalytically active carbene complex than terminal alkenes. If, however, terminal alkenes are to be prepared, selfmetathesis of the product (to yield ethene and a symmetrically disubstituted ethene) is likely to become a serious side reaction. This side reaction can be suppressed by conducting the metathesis reaction in the presence of ethene [782,783]. 

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). 

Dihydropyrroles have recently become readily available by ring-closing metathesis. For this purpose, N-acylated or N-sulfonylated bis(allyl)amines are treated with catalytic amounts of a ruthenium carbene complex, whereupon cyclization to the dihydropyrrole occurs (Entries 6 and 7, Table 15.3 [30,31]). Catalysis by carbene complexes is most efficient in aprotic, non-nucleophilic solvents, and can also be conducted on hydrophobic supports such as cross-linked polystyrene. Free amines or other soft nucleophiles might, however, compete with the alkene for electrophilic attack by the catalyst, and should therefore be avoided. 

Ring-closing metathesis is well suited for the preparation of five- or six-membered heterocycles, and has also been successfully used to prepare tetrahydropyridines on insoluble supports (Entries 1 and 2, Table 15.23). Because metathesis catalysts (ruthenium or molybdenum carbene complexes) are electrophilic, reactions should be conducted with acylated amines to avoid poisoning of the catalyst. 

Treatment of enynes 35 and 36 with first generation Grubbs carbene under the above diene ring-closing metathesis conditions did not furnish the desired spiro-cycles. Next, trials of cyclization were attempted by using its imidazolidinylidene... 

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