Cyclotrimerization intramolecular

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]. 

This rhodium-catalyzed intramolecular cyclotrimerization method has been utilized as the key step for the synthesis of the marine illudalane sesquiterpenoid, alcyopterosin E, 51, which has a fused 5-6-5 ring system as illustrated in Scheme 7.15 [37]. 

Intermolecular cyclotrimerization of alkynes using Wilkinson s catalyst has also afforded substituted carbazole derivatives. This reaction was extended to an intramolecular version by offering the possibility for a six-membered ring annotation that cannot be achieved easily in the corresponding intermolecular version. Intramolecular cyclotrimerization is completely regioselective due to an additional tether. 

Triynes 261 in which the alkyne linkages are properly spaced can undergo intramolecular cyclotrimerization to aromatics 262 and 263 in the presence of Ziegler-type catalysts-"h... 

An intramolecular cyclotrimerization has been reported by condensation of a diyne with an alkyne in the presence of a palladium, molybdenum, nickel, rhodium, iridium, or ruthenium catalyst. Triynes have been... 

The ifaodium-catalyzed intramolecular cyclotrimerization of 1,6,11-triyne 419, forming 5-6-5 fiised-ring system 420, has been extensively studied (Scheme 2-41, eq. i).[220b,276] reaction has also been used as the key step in the synthesis of a marine illudalane sesquiterpenoid, alcyopterosin E (423) (Scheme 2-41, eq. 2)P as well as in die asymmetric synthesis of chiral diphosphine ligands 425 (Scheme 2-41, eq. 3). ... 

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 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. 

Fully intramolecular [2 + 2 + 2] cyclization of triynes affords tricyclic products with complete chemo- and regioselectivity. Despite this advantage, this method is underdeveloped, which is probably due to the diminished accessibility of the triyne substrates. Peters and Blechert reported the first ruthenium-catalyzed fully intramolecular cyclotrimerization using the metathesis cascade strategy with Grubbs catalyst [23]. Later, Yamamoto et al. demonstrated that complex 6 efficiently catalyzes the cyclization of various triynes [14]. Examples of 1,6,11-triyne cyclization are summarized in Table 3.11. As an example, diether 58 (X = = O, R = H) underwent [2 + 2 + 2]... 

The alcyopterosins represent an interesting set of illudalanes that were isolated from deep-sea soft corals and whose members represent the first nitrate esters to be found in any natural product [10]. The rhodium-catalyzed intramolecular cyclotrimerization method has been utilized here to gain access to the 5-6-5 and 6-6-5, as well as the bicyclic ring systems of this set of marine illudalanes (Schemes 7.5 to 7.7). The synthesis of enantiopure triyne 21, as needed for alcyopterosin E (22), was straightforward, starting from readily available L-ascorbic acid (17) and isophorone (20), to provide the alkyne building blocks 18 and 19 in seven and six steps, respectively (Scheme 7.5) [11]. 

As little as 3 to 5 mol % of RhCl(PPh3) induced the intramolecular cyclotrimerization reaction of triyne 43 to provide the tricyclic benzocylobutane 44. After attachment... 

Scheme 2.29 Intramolecular cyclotrimerization triynes 2.84 catalyzed by N-heterocyclic carbene-CoCli/Zn or -FeCb/Zn.

Saino, N., Kogure, D. and Okamoto, S. (2005) Intramolecular cyclotrimerization of triynes catalyzed by N-heterocyclic carbene-CoCli/Zn or -FeCb/Zn. Organic Letters, 7(14), 3065-3067. 

Sakurai, H., Nakadaira, Y., Hosomi, A., Eriyama, Y., Hirama, K. and Kabuto, C. (1984) Intramolecular cyclotrimerization of macrocyclic and acyclic triynes with Group 6 metal carbonyls. The formation of fulvene and benzene. Journal of the American Chemical Society, 106(26), 8315-8316. 

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