RuCp complex

Zheng et al. treated potassium [l,2,4]diazaphospholides, obtained from the reaction of 3,5-disubstituted-[l,2,4]diazaphospholes with metallic potassium in THF, with [Cp RuCl]4 to afford [(T75-dp)RuCp ] type pseudoruthenocene complex (106) (Scheme 33). Sandwich structure with almost eclipsed orientation of two n-bonded ligands has been confirmed by X-ray crystal structure determination [110], Catalytic application of [(rf-dp)RuCp ] complexes in the Heck reaction has also been investigated [111]. 

The (arene)RuCp complexes share many characteristics with the analogous iron compounds such as their robustness, stability to air and mild oxidants, and the photo lytic cleavage of the arene metal bond. It has to be pointed out though that there are substantial differences in both the efficiency of the photolytic cleavage (Fe>Ru) and the stability of the resulting cationic CpM(solvate)3 complexes (Ru>Fe).As will be detailed below the latter will form the basis for the best synthetic routes to the title compounds. 

Photolytic cleavage of the benzene-Ru bond of 105 in acetonitrile gives a quantitative yield of the pale orange, crystalline complex [CpRu(CH3CN)3] [PFg] (106). The acetonitrile ligands in 106 are labile and the compound therefore serves as a convenient transfer agent for the CpRu" fragment. A selection of (arene)RuCp complexes made by this route is assembled in Scheme 11. 

Scheme 11 Synthesis of (arene)RuCp+ complexes from (arene)Ru(CH3CN)3+...

Addition/Oxidation with Cationic (Arene)RuCp Complexes. 64... 

Analogous chemistry with Ru complexes is much less developed. Hydride and phenyllithium add to (arene)RuCp complexes in good yields [128]. Inter- [127] and intramolecular [129] enolate additions are also successful. The resulting species can be rearomatized using DDQ in good yield demetallation was a competing process (15% yield of the free arene), Eq. (34) [127]. 

At the end of this chapter, a few cationic arene-RuCp complexes will be mentioned as well, because such complexes possess a unique potential for arylether formation and have thus found convincing application in total synthesis as well. 

In conclusion, q -arene transition metal complexes have demonstrated their unique potential for organic synthesis. In particular, planar-chiral q -arene-Cr(CO)3 complexes are valuable building blocks for the diastereo- and enanti-oselective synthesis of complex natural products and related bioactive compounds. Highly original and competitive overall syntheses of various classes of natural products have been developed. The expenditure spent for the introduction of the metal fragment pays off especially in those cases, where the various chemical and stereochemical effects of the metal unit can be exploited in several subsequent transformations. Besides arene-Cr(CO)3 complexes, cationic arene-RuCp complexes have also been applied in synthesis, especially as they allow for efficient arylether formation under mild conditions. 

Another type of structure which has been examined are [RuCp]" complexes of 5-chloroindoles <88OM660>. These complexes undergo nucleophilic substitution by amine, alkoxide, thiolate and malonate nucleophiles (Scheme 133). 

Fig. 18 Structures involved in the inner-sphere hydrogenation by the Shvo catalyst (a) franial-dehyde approach to the RuCp complex, (b) TS for the hydrogen transfer to the carbonyl, (c) alcohol interaction with the imsaturated Ru complex...

More recently, spirocyclizations utilizing (q -arene)RuCp+ complexes have been reported [102]. Treatment of Ru(II) complex 97 with NaH in the presence of an aldehyde initiates tandem stereoselective nucleophilic aromatic addition-Horner-Wadsworth-Emmons olefination to deliver stable cyclohexadienyl complex 98 (Scheme 15.33) [103]. Dearomatization was completed via formal oxidation of the cyclohexadienyl ligand accompanied by addition of an external nucleophile. The stereodirecting effects of the metal center and the preexisting stereocenter completely control diastereoselectivity, resulting in formation of optically pure 99 with recovery of the CpRu fragment. 

Studies carried out for some of our RuCp complexes by inductively coupled plasma mass spectrometry (ICP-MS) to quantify the amount of ruthenium ion in the several cell fragments, after incubation with different cancer cell lines, showed that ruthenium preferentially accumulates in the cell membrane. Nevertheless, a significant amount of this metal is also found in cytosol and nucleus. Comparison with results obtained for cisplatin reference, used in our studies in the same experimental conditions, reveals that Pt barely reaches these three compartments. 

Our most recent studies by ESI-MS of RuCp complexes with these proteins show significant interaction and importantly reveal that ruthenium compounds preserve their initial structure. 

The free amino group of 4-0-methyldopamine and 4-0-methyltyramine react as nucleophiles in a chemoselective manner with [RuCp] -complexed p-substituted chloro-arenes. As a consequence, it is not necessary to use protecting groups for the synthesis of peptides with alternating amide and diaryl ether bonds. 

The (arene)Cr(CO)3 complex is neutral and so is not a very powerful electrophile. In the styrene case, when an ester is placed at the other end of the alkene, Michael addition to the acrylate unit occurs in high yield. Even with a chlorine leaving group on the arene complex (see Section 14.3.5), no local addition was observed [201]. Comparable examples of cationic RuCp complexes with cyanide and thiophenol as the nucleophile give examples where the nucleophile has added to the face of the ligand that carries the metal, and it is proposed that this is the favored kinetic approach [202]. 

Typically, however, heteroatom nucleophiles have been employed in these metal-promoted S Ar reactions, as in the formation of an aryl ether derivative of tyrosine using the Mn(CO)3 complex of chlorobenzene [317]. This type of procedure has been used to great effect (Table 14.1 entries 26 and 27) in key cyclization steps in syntheses of the ACE inhibitor K-13 (100) [318], and a portion of ristocetin (102). Two different complexed haloarene amino acid derivatives were used in the ristocetin case [179,319]. These examples, which employ j/ RuCp complexes 101,... 

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