Intermolecular cross-cyclotrimerization

Transition-metal-catalyzed intermolecular [2+2+2] cyclotrimerization of alkynes to benzenes has been extensively studied with several catalyst systems involving palladium, cobalt, nickel, rhodium, and other transition metals. This methodology can be applied to the preparation of polysubstituted benzenes. The major challenge of this transformation is control of regioselectivity of unsymmetrical alkynes, particularly in the cross-cyclotrimerization of two or three alkynes. 

In 1996, Garcia et al. reported cyclotrimerization of (trifluoromethyl)acetylene 390a using a bimetallic rhodium complex at room temperature to afford l,3,5-/ra (trifluoromethyl) benzene 391 in high yield (Scheme 2-33). Recently, Tanaka et al. reported a chemoselective and regioselective intermolecular cross-cyclotrimerization of two different alkynes using a cationic Rh complex as catalyst (Scheme 2-34). ° ... 

Typical procedure for the intermolecular cross-cyclotrimerization of dialkyl acetylene-dicarboxylates and terminal monoynei ... 

Axially chiral biaryls are an important class of molecules primarily because of their biological activity, as well as their use as chiral ligands. Although enantioselective cyclotrimerization of 1,6-diynes with alkynes or nitriles catalyzed by transition metals has been developed, it was difficult to realize the intermolecular cross-cyclotrimerization process with three alkynes. However, a cationic Rh-complex with (5)-H8-BINAP was found to catalyze effectively the regioselective and enantioselective intermolecular cross-cyclotrimerization of two alkynes 392 and 394 to give chiral biaryls 395 with 89-96% ee in good yields (Scheme 2-35). ... 

Recently, Tanaka and co-workers reported a chemo- and regioselective intermolecular cross-cyclotrimerization of alkynes 67 and 68 using cationic Rh complexes (Scheme 38) (77). 

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... 

The regiochemical product distribution of the co-cyclization of two or three different alkynes occurs statistically. In some cases carefully controlled reaction conditions allow isolation of a main product from mixed cyclotrimerizations. For example, l,2,3,4-tetraphenyl-5,6-diethylbenzene can be obtained from cobalt-catalyzed reaction of tolane and 3-hexyne in good yield [62]. The first example of an intermolecular, regiospecific cross-benzannulation reaction catalyzed by Pd(PPh3)4 was reported by Yamamoto [63]. The reaction of 2-alky 1-but-l-ene-3-yne with disubstituted diynes leads exclusively in high yields to... 

Use of (PCy3)2Cl2Ru=CHPh (1) in Other Synthetie Transformations. As well as finding widespread use in metathesis, (1) has found applications as a catalyst for other important reactions. These include hydrosilylation of alk3Ties dehydrogenative condensation of alcohols and hydrosilylation of carbonyls intermolecular cyclotrimerization of terminal alkynes conversion of triynes to benzene derivatives Kharasch additions (Z)-selective cross-dimerization of ary-lacetylenes with silylacetylenes and hydrogenation of natural rubber. ... 

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