Partially Intramolecular Cyclotrimerizations

Partially intramolecular reactions have the advantage of using readily accessible diynes and monoalkynes as substrates. However, problems with chemo- and regios-electivity remain. Facile dimerization of the diynes is a serious obstacle that must be overcome by using a large excess of the monoalkyne component. In 20(X), Yamamoto 

Young et al. developed solid-supported [2 - - 2 - - 2] cycloadditions in pursuit of a library synthesis using immobilized diyne substrate 55 with monoalkynes in the presence of catalyst 6 (Table 3.10) [42], This method avoids competitive selfcycloaddition of the expensive diyne substrate. In addition, immobilization facilitates the separation of the cross-cycloadducts from the catalyst, unreacted reagents, and 

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Axially chiral biaryls are an important class of molecules for both biologically active compounds and chiral ligands (78-80). The most common approach to obtain biaryls is by aryl coupling followed by resolution of the racemic product to afford enantiopure biaryls. Even though enantioselective partial intramolecular cyclotrimerization of diyne with alkynes (81,82) or nitriles (83) were developed with various transitional metals, it was difficult to carry out complete intermolecular reaction. Using a cationic chiral rhodium complex as catalyst, a regioselective intermolecular cross-cyclotrimerization of alkynes 72 and 73 for... 

Based on this work, Itoh and co-workers developed ruthenium(n)-catalyzed [2 + 2 + 2]-cyclotrimerizations of 1,6-diynes 174 and electron-deficient nitriles (Equation (34)),368>368a These partially intramolecular cycloadditions proceed through ruthenacycle intermediates as well. The importance of using electronically activated nitriles is underlined by the fact that acetonitrile and benzonitrile gave only very low yields. 

It is possible to carry out the [2+2+2] cyclotrimerization reaction in a regioselective manner by using a partially or completely intramolecular approach. Rhodium-catalyzed intramolecular cyclotrimerization of 1,6,11-triynes, which construct fused 5-6-5 ring-systems, has been studied extensively [33-36]. Cyclization of 1,6,11-triyne 47 catalyzed by RhCl(PPh3)3, gives the tricyclic benzene 48 in good yield (Eq. 14) [33a]. 

The reactions that yield benzene rings can be categorized further into the following types according to the substrates involved (1) intermolecular cycloaddition of three alkynes (cyclotrimerization), (2) partially intramolecular cycloaddition ofdiynes with alkynes, and (3) fully intramolecular cyclotrimerization of triynes. In the next section, the synthetic routes to benzene derivatives using ruthenium-catalyzed cycloaddition are surveyed according to these classifications. Classic examples of [2 + 2 + 2] alkyne cycloadditions using stoichiometric ruthenium mediators are included since they provide useful information on the further development of ruthenium catalysis. 

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