Ruthenium alkylidene complexes, synthesis

Scheme 6. Synthesis of ruthenium-alkylidene complexes starting at the azolium salt without isolating the NHCs.

In situ deprotonation combined with a substitution of a phosphine ligand was reported as a convenient way for the synthesis of ruthenium-alkylidene complexes (Scheme For imidazolidin-2-ylidenes, this is the only way... 

Olefin isomerization catalyzed by ruthenium alkylidene complexes can be applied to the deprotection of allyl ethers, allyl amines, and synthesis of cyclic enol ethers by the sequential reaction of RCM and olefin isomerization. Treatment of 70 with allyl ether affords corresponding vinyl ether, which is subsequently converted into alcohol with an aqueous HCl solution (Eq. 12.37) [44]. In contrast, the allylic chain was substituted at the Cl position, and allyl ether 94 was converted to the corresponding homoallylic 95 (Eq. 12.38). The corresponding enamines were formed by the reaction of 70 with allylamines [44, 45]. Selective deprotection of the allylamines in the presence of allyl ethers by 69 has been observed (Eq. 12.39), which is comparable with the Jt-allyl palladium deallylation methodology. This selectivity was attributed to the ability of the lone pair of the nitrogen atom to conjugate with a new double bond of the enamine intermediate. 

The lessons learned from these complexes were eventually applied to the synthesis of well-defined ruthenium alkylidenes 8 and 9. Although they were insoluble in water, these alkylidenes could be used to initiate the living ROMP of functionalized norbornenes and 7-oxanorbomenes in aqueous emulsions. Substitution of the phosphine ligands in 9 for bulky, electron-rich, water-soluble phosphines produced water-soluble alkylidenes 10 and 11, which served as excellent initiators for the ROMP of water-soluble monomers in aqueous solution. These new ruthenium alkylidene complexes are powerful tools in the synthesis of highly functionalized polymers and organic molecules in both organic and aqueous environments. 

Fig. 4.36. Synthesis of mixed NHC-phosphine ruthenium alkylidene complexes.

Scheme I. Synthesis of homobimetallic ruthenium-alkylidene complexes bearing phosphine ligands.

Scheme 10.13 Direct synthesis of NHCP ruthenium alkylidene complexes. The clashed line in complex 58a does not indicate an agostic interaction but implies the steric shielding of the free coordination site as a consequence of the distinct topology of the NHC group.

Scheme 10.14 Synthesis of NHCP ruthenium alkylidene complexes by introducing the alkylidene ligand with diazo compounds.

Initial reports of cross-metathesis reactions using well-defined catalysts were limited to simple isolated examples the metathesis of ethyl or methyl oleate with dec-5-ene catalysed by tungsten alkylidenes [13,14] and the cross-metathesis of unsaturated ethers catalysed by a chromium carbene complex [15]. With the discovery of the well-defined molybdenum and ruthenium alkylidene catalysts 3 and 4,by Schrock [16] and Grubbs [17],respectively, the development of alkene metathesis as a tool for organic synthesis began in earnest. 

Metathesis polymerization has become an important tool for polymer synthesis and has even attracted a Nobel Prize [46-49]. Acyclic diene molecules are capable of undergoing intramolecular and intermolecular reactions in the presence of appropriate transition metal catalysts, for example, molybdenum alkylidene and ruthenium carbene complexes. The intramolecular reaction, called ring-closing olefin metathesis (RCM), leads to cyclic compounds and the intermolecular reaction, called acyclic diene metathesis (ADMET) polymerization, leads to oligomers and polymers. Altering the dilution of the reaction mixture can to some extent control the intrinsic competition between RCM and ADMET. 

More recentiy, Ruiz et al. have developed the synthesis of the ruthenium(II) complex 28 [154]. This makes use of an appropriate combination of previous strategies. The ruthenium atom is stereogenic and this leads to a mixture of dia-stereoisomers, which are eight times more active than cisplatin on T47D breast cancer cell line. This approach can be extended to include complexes of rhodium and iridium [155], and other variants of the method have been used with ruthenium [156]. Alkylidyne and alkylidene derivatives of osmium, exemplified by molecule 29, have been reported [157], but as yet they have not been evaluated biologically. 

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