Ruthenium chemoselectivity

Scheme 94 Total synthesis of the natural compound dehydrohomoancepsenolide (473) through sequential application of chemoselective ruthenium-catalyzed RCM and tungsten-catalyzed alkyne homodimerization [191]...

The use of stoichiometric ruthenium-NHC complexes generated in situ from [Ruljd-COCKp-cymene)], an imidazohnm salt [4] or an imidizol(idin)ium-2-carboxylate [4] has been applied in the cyclopropanation of styrene 5 with ethyl diazoacetate (EDA) 6 (Scheme 5.2). No base was necessary when imidazolium-2 carboxylate were employed. The diastereoselectivity was low and the cis/trans ratio was around 50/50 (Table 5.1). Although the diastereoselectivity was moderate, the reaction was highly chemoselectivity as possible side reactions (homologation, dimerisation and metathesis) were totally or partially suppressed. 

High chemoselectivity is observed in this ruthenium-catalyzed isomerization of allylic alcohols. Simple primary and secondary alcohols and isolated double bonds are not affected by these catalysts. Furthermore, free hydroxy group is essential for this catalysis. The reaction of l-acetoxycyclododec-2-ene-4-ol furnished 4-acetoxycyclododecanone in high yield (Scheme 14).37... 

A ruthenium(n)-indenyl complex, which is an efficient catalyst for the isomerization of allylic alcohols, is also an effective catalyst for the isomerization of propargylic alcohols to both a,/3-enals and a,/ -enones (Scheme 57).96 In this reaction, the addition of 20—40 mol% InClj is highly effective. The reaction exhibits extraordinary chemoselectivity and a variety of functional groups are unaffected, which allows a highly efficient synthesis of dienals (R1 =Me2C = CH, R2 = H). 

Ruthenium catalysts have also been used in this context.200,201 In particular, the cationic ruthenium complex, CpRu(CH3CN)3PF6, in conjunction with carboxylic acid ligand 3, has been used to achieve the remarkably chemoselective allylation of a variety of alcohols via dehydrative condensation with allyl alcohol (Equation (50)).202 It is worth noting that this transformation proceeds with 0.05 mol% catalyst loading and does not require the use of excess allyl alcohol. 

The current research areas with ruthenium chemistry include the effective asymmetric hydrogenation of other substrates such as imines and epoxides, the synthesis of more chemoselective and enantioselective catalysts, COz hydrogenation and utilization, new methods for recovering and recycling homogeneous catalysts, new solvent systems, catalysis in two or three phases, and the replace-... 

It has been shown previously how water-soluble rhodium Rh-TPPTS catalysts allow for efficient aldehyde reduction, although chemoselectivity favors the olefmic bond in the case of unsaturated aldehydes [17]. The analogous ruthenium complex shows selectivity towards the unsaturated alcohol in the case of crotonaldehyde and cinnamaldehyde [31]. 

The ruthenium-phosphine-diamine catalysts exhibit high turnover numbers and frequencies, and near-perfect chemoselectivity for ketone/aldehyde over... 

As terminal alkynes and ethynyl alcohols are the convenient sources to generate ruthenium vinylidene and allenylidene intermediates, many carbocyclizations have been achieved via nucleophilic addition and other activations at the two intermediates. Most reported carbocyclizations appear to be synthetically useful, not only because of their chemoselectivities but also because of their tolerance toward organic functional groups. Additional examples of catalytic carbocyclization based on ruthenium vinylidenes are still growing, and on the basis of the concepts developed here one can expect to see many new applications in the near future. 

The remarkable chemoselectivity of ruthenium NHC catalysts to bind olefins in the presence of heteroatomic moieties makes them ideally suited for use in one-pot sequential reactions, as they are stable toward a variety of reaction conditions and reagents and, often, their presence does not impede subsequent transformations. The... 

Ir/tppts catalysts exhibit almost the same selectivity as Ru/tppts in the hydrogenation of a,p-unsaturated aldehydes albeit with approximately 70 times lower rates.485 In sharp contrast to the ruthenium and iridium based tppts catalysts, RhJ tppts complexes catalyse the chemoselective hydrogenation of a,fl-unsaturated aldehydes to the corresponding saturated aldehydes (Figure 14, III).54-485... 

Mechanisms have been proposed for ruthenium(III)-catalysed oxidation of leucine by acid bromate133 and for the chemoselective oxidation of vicinal diols to a-hydroxy ketones with NaBrC>3/NaHS03 reagent.134... 

Treatment of l-(2,-iodoethynylphenyl)-2-propyloxirane with TpRuPPh3(CH3CN)2 PF6 catalyst produced l-iodo-2-naphthol exclusively in DMF, but 2-iodobenzo[d]oxepin in benzene (Scheme 83).125 The solvent-dependent chemoselectivity is considered consistent with a solution equilibrium between ruthenium-2-iodoalkyne and ruthenium-2-iodovinylidene intermediates. In this cyclization, the active species is a ruthenium-7r-iodoalkyne in benzene, but a ruthenium-2-iodovinylidene in DMF. 

A palladium-catalyzed intramolecular benzannulation of bis-enynes 1135 proceeds chemoselectively to afford dihydroisocoumarins 1136 (Equation 441) <2002JOC2653>. A reaction sequence involving ruthenium-catalyzed yne-ene cross-metathesis of a polystyrene supported undecynoic acid ester followed by a Diels-Alder cycloaddition reaction with DMAD provides the basis for a combinatorial approach to dihydroisocoumarins featuring a variety of side chains at C-6 and C-8 <1999SL1879>. 

The results under flow conditions showed a slight improvement in nearly all areas compared with the representative batch reaction - importantly, both the yield and chemoselectivity were significantly improved - but all reactions still produced a significant amount of the dimerized by-products (ethyl fumarate (57) and ethyl maleate (58)). The solventless system allowed larger quantities of material to be prepared, whereas the scC02 system provided products contaminated with only traces of ruthenium (less than 1 ppm). 

The previous examples have established ruthenium-catalyzed atom-transfer reactions as a valuable addition to the list of synthetic methods available in fine chemistry. The potential of these systems is obvious, but sometimes their applicability is limited by rather poor catalytic activity and/or selectivity, particularly when it comes to the chemoselectivity of the addition and the concurrent formation of telomers. Hence, the need to extend the range of possible substrates and to perform the reactions under milder conditions led to the search for new catalytic systems with improved performances. Yet, the application of ruthenium catalysis to radical reactions remains a relatively unexplored and new field. 

Alkenylsilanes, mainly vinyl silanes and allyl silanes or related compounds, being widely used intermediates for organic synthesis can be efficiently prepared by several reactions catalyzed by transition-metal complexes, such as dehy-drogenative silylation of alkenes, hydrosilylation of alkynes, alkene metathesis, silylative coupling of alkenes with vinylsilanes, and coupling of alkynes with vinylsilanes [1-7]. Ruthenium complexes have been used for chemoselective, regioselective and stereoselective syntheses of unsaturated products. 

The oxidation of N-methylamines provides various useful methods for organic synthesis. Selective demethylation of tertiary methylamines can be carried out by the ruthenium-catalyzed oxidation and subsequent hydrolysis (Eq. 3.71). This is the first synthetically practical method for the N-demethylation of tertiary amines. The methyl group is removed chemoselectively in the presence of various alkyl groups. 

Proton abstraction of the polar C-H bond with base is a well-established heteroly-tic C-H bond cleavage to obtain carbanion. Ruthenium complexes can act as a base in nonpolar media to provide highly selective catalyses, as in the Murahashi aldol and Michael reactions. These reactions are highly chemoselective under neutral and mild conditions, where cyanoesters preferentially react over 2,4-pentanedione with nucleophiles (Scheme 14.12) [26]. The mechanistic basis of this reaction is described in Section 14.2.2. 

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