Ruthenium-Catalyzed Cyclizations

Carbon nucleophiles can also add to in situ generated vinylidene species. Thus, ruthenium-catalyzed cyclizations of dienylalkynes produced arene derivatives [55] (Eq. 41). 

Schmidt B. Ruthenium-catalyzed cyclizations more than just olefin metathesis Angew. Chem. Int. Ed. 2003 42 4996-4999. Vemall AJ, Abell AD. Cross metathesis of nitrogen-containing systems. Aldrichim. Acta 2003 36 93-105. 

Recently, Nagashima and associates developed a new route to y-lactams by the ruthenium-catalyzed cyclization of /V-allyltrichloroacetamides [24], Also, Stork and Mah reported the radical cyclization of /V-protected haloacetamides to yield /V-protected lactams. The protecting groups can then be easily removed under a range of different conditions [25]. This efficient radical cyclization route to d.s-fused pyrrolidones and piperidones is interesting because of the widespread occurrence of related systems in natural products [26]. 

Nagashima, H., Wakamatsu, H., Ozaki, N., Ishii, T., Watanabe, M., Tajima, T., Itoh, K. Transition metal catalyzed radical cyclization new preparative route to y-lactams from allylic alcohols via the [3.3]-sigmatropic rearrangement of allylic trichloroacetimidates and the subsequent ruthenium-catalyzed cyclization of N-allyltrichloroacetamides. J. Org. Chem. 1992, 57, 1682-1689. 

The ruthenium-catalyzed cyclization of epoxy iodoalkynes shows a very intriguing solvent dependence <05OL1745>. The authors rationalize this solvent dependence as a result of two different ruthenium intermediates. In a polar solvent such as DMF an iodovinylidene species is formed followed by attack of the epoxide oxygen to eventually lead to naphthalene 91 in 88% yield. A nonpolar solvent such as benzene favors the formation of a p-iodoalkyne ruthenium species. Attack of this species by the epoxide oxygen leads to formation of oxepin derivative 92 in 78% yield. 

Introduction of the second nitrogen substituent is accomplished by mesylation of the secondary alcohol and subsequent displacement (with inversion) by sodium azide. Hydrolysis of the carbamate, hydrogenolysis of the N-benzyl group with concomitant reduction of the azide group, protection of the newly formed amino group with a Cbz, and ruthenium-catalyzed cyclization gives the hemiacetal 493, which is then carried on to the target molecule 494. 

Moreover, in 2008, a novel ruthenium-catalyzed cyclization based on a combination of isocyanates, alkynes, and CO was developed by the group of Rondo et al. [17]. Polysubstituted maleitnides could be obtained in excellent yields under CO at atmospheric pressure with low catalyst loading (Scheme 1.6). 

In addition to cobalt catalysts, ruthenium catalysts were applied in [2 + 2 + 2] cycloaddition reactions as well. In 2001, Itoh and coworkers reported a ruthenium-catalyzed cyclization of 1,6-diynes with dicyanides to produce the desired bicyclic pyridines in good yields [28]. By applying Cp Ru(cod)Cl (Cp = pentamethylcyclopentadienyl) as the catalyst, good yields of the products can be achieved (Scheme 3.12). Meanwhile, they explored the catalyst system in cyclization of 1,6-diynes with electron deficient nitriles as well. The desired bicyclic pyridines can be isolated in moderate to high yields [29]. Later on, in 2005, Yamamoto and coworkers performed systematic studies on this... 

Scheme 49 Ruthenium-catalyzed cyclization of 2-allcyl-l-ethynylbenzene carrying a silyl ether group...

Similarly, acetalic C-H bond could be exploited as hydride donor as well, and via ruthenium-catalyzed cyclization of linear alkynyl acetals 181, spirobicycles 182 could be furnished in fairly good yield (Scheme 69) [76], along with the formation of linear hydroxyester 183, which was generated by hydrolysis of intermediate I. Notably, rigid cyclic acetal afforded a higher yield of spiro compound in comparison to the linear acetals [96]. 

Scheme 81 Ruthenium-catalyzed cyclization of 2-alkyl-1-ethynyl-benzenes...

A series of (Z)-3-methyleneisoindolin-l-ones were generated using a ruthenium-catalyzed cyclization (Scheme 3.89) [92]. Benzonitriles and activated alkenes such as acrylates served as the substrates in these reactions, and moderate to good yields were obtained. 

Scheme 7.7 Proposed mechanism for ruthenium-catalyzed cyclization of amines with alkynes.

Table 2.18 Ruthenium-catalyzed cyclization via a twofold benzannulation.

Merlic, C.A. and Pauly, M.E. (1996) Ruthenium-catalyzed cyclizations of dieny-lalkynes via vinylidene intermediates. Journal of the American Chemical Society, 118(45), 11319-11320. 

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