Ruthenium reactions with nucleophiles

The suggested catalytic cycle for the diamine catalysts indicates that the NH group of the diamine plays a direct role in the hydride transfer through a six-membered TS.53 A feature of this mechanism is the absence of direct contact between the ketone and the metal. Rather, the reaction is pictured as a nucleophilic delivery of hydride from ruthenium, concerted with a proton transfer from nitrogen. 

The synthesis introduced by Bruce et al. starts from butadiynyl lithium [14]. The addition of HBF4 to solutions of buta-l,3-diynyl ruthenium complex 3 was proposed to afford the butatrienylidene cation 4 by protonation of the terminal carbon atom of the butadiynyl ligand. Complex 4 could neither be isolated nor spectroscopically detected. It readily decomposed by reaction with even traces of water in the air by nucleophilic attack of H2O on the cationic center (Scheme 3.2). 

The CM of olefins bearing electron-withdrawing functionalities, such as a,/ -unsaturated aldehydes, ketones, amides, and esters, allows for the direct installment of olefin functionality, which can either be retained or utilized as a synthetic handle for further elaboration. The poor nucleophilicity of electron-deficient olefins makes them challenging substrates for olefin CM. As a result, these substrates must generally be paired with more electron-rich crosspartners to proceed. In one of the initial reports in this area, Crowe and Goldberg found that acrylonitrile could participate in CM reactions with various terminal olefins using catalyst 1 (Equation (2))." Acrylonitrile was found not to be active in secondary metathesis isomerization, and no homodimer formation was observed, making it a type III olefin. In addition, as mentioned in Section 11.06.3.2, this reaction represents one of the few examples of Z-selectivity in CM. Subsequent to this report, ruthenium complexes 6 and 7a were also observed to function as competent catalysts for acrylonitrile... 

Cyclic sulfites (68) also are opened by nucleophiles, although they are less reactive than cyclic sulfates and require higher reaction temperatures for the opening reaction. Cyclic sulfite 77, in which the hydroxamic ester is too labile to withstand ruthenium tetroxide oxidation of the sulfite, is opened to 78 in 76% yield by reaction with lithium azide in hot DMF [82], Cyclic sulfite 79 is opened with nucleophiles such as azide ion [83] or bromide ion [84], by using elevated temperatures in polar aprotic solvents. Structures such as 80 generally are not isolated but as in the case of 80 are carried on (when X = N3) to amino alcohols [83] or (when X = Br) to maleates [84] by reduction. Yields are good and for compounds unaffected by the harsher conditions needed to achieve the displacement reaction, use of the cyclic sulfite eliminates the added step of oxidation to the sulfate. 

The polarisation produced by co-ordination to the metal may be transmitted through a conjugated system. Michael addition reactions of nucleophiles to TV-bonded acrylonitrile are known, and provide a convenient method for the preparation of derivatives. A wide range of nucleophiles may be used in these conjugate additions. For example, the anion of nitromethane (generated in situ) reacts with the ruthenium(m) complex [Ru(NH3)5N=CCH=CH2)]3+, 4.6, to yield a complex of 4-nitrobutyronitrile (Fig. 4-18). 

Polymer-supported synthesis of 1,3-dienes by efficient ruthenium-catalyzed in-termolecular enyne metathesis has been reported by Schiirer and Blechert [99]. The polystyrene resin, containing a propargyl ester moiety, was reacted with functionalized alkene in the presence of Cl2(PCy3)2Ru(=CHPh). The dienes obtained were cleaved from the polymer support using a paladium-catalyzed reaction with different nucleophiles (Eq. 57). 

The vast majority of work exploring the reactivity of ruthenium viny-lidene complexes has focused on the attack of alcohols at the electrophilic a carbon of monosubstituted vinylidenes, resulting in the formation of ruthenium alkoxycarbene complexes. Bruce and co-workers have determined, for example, that the phenylvinylidene complex 80 is slowly transformed in refluxing MeOH to the methoxycarbene complex 82 in good yield (73,83). The mechanism for this reaction must involve initial attack of the alcohol at the electrophilic Ca to form a transient vinyl intermediate 81 which is rapidly protonated at the nucleophilic Cp, generating the product carbene 82 [Eq. (79)]. In contrast to monosubstituted vinylidene complexes, disubstituted vinylidene complexes are generally unreactive to nucleophiles even the relatively small dimethylvinylidene complex 83 shows no reaction with MeOH after 70 hours at reflux [Eq. (80)]. 

Benzene cyclopentadienyl ruthenium(II) complex 125 undergoes nucleophilic addition at the arene ligand via the addition of sodium borohy-dride or phenyllithium. Reaction with phenyllithium gives the exo-phenyl cyclohexadienyl derivative 249 in 89% yield (154) [Eq. (32)]. 

Since the Lewis acid-promoted reactions of the oxidized products with nucleophiles give the corresponding N-acyl-a-substituted amines efficiently, the present reactions provide a versatile method for selective C-H activation and C-C bond formation at the a-position of amides [138]. Typically, TiCl4-promoted reaction of a-t-butyldioxypyrrolidine 66, which can be obtained by the ruthenium-catalyzed oxidation of l-(methoxycarbonyl)pyrrolidine with f-BuOOH, with a silyl enol ether gave keto amide 67 (81%), while the similar reaction with less reactive 1,3-diene gave a-substituted amide 68 (Eq. 3.80). 

The reaction can be rationalized by assuming the mechanism which involves 0x0-ruthenium complex (Scheme 3.9). Hydrogen abstraction with oxo-ruthenium species gives phenoxyl radical 73, which undergoes fast electron transfer to the ruthenium to give a cationic intermediate 74. Nucleophilic reaction with the second molecule of t-BuOOH gives the product 72. 

The ambiphilic character of JT-allylmthenium complexes is in remarkable contrast to palladium chemistry [29]. A series of (jt-C3H5)RuX(CO)3 (X = Br, OAc or OTf) complexes prefer the attack of electrophiles such as aldehydes as well as the attack of nucleophiles such as NaCH(C02Me)2, while Jt-allylpalladium complexes react exclusively with nucleophiles. Thus, stoichiometric reactions of Jt-allylmthenium complex with benzaldehyde and the sodium salt of diethyl malonate afford the corresponding homoallyl alcohol and allylmalonate, respectively (Scheme 5.1). The carbonyl ligand plays a very important role, and ambiphilic reactivity is realized only in ruthenium complexes bearing a carbon monoxide ligand. 

Although few investigations have been made to determine the stereochemical course of the reaction of Jt-allylmthenium complexes with nucleophiles, Harman and coworkers recently reported that the reaction with soft nucleophiles exclusively proceeded via an anti mechanism [58]. The observations described here, together with information in the literature, suggest that the ruthenium-catalyzed allylic substitution reaction proceeds via a double inversion (i.e., a net retention) mechanism. 

Dixneuf suggested that this reaction proceeds via the nucleophilic attack of a carbamate anion to the ruthenium vinylidene intermediate generated by the reaction of ruthenium complexes with terminal acetylene. The details of this reaction are discussed in Chapter 8. 

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. 

The reactivity of hexachloride ruthenium (II) precursors in the reactions of nucleophilic substitution is somewhat lower than that of their analogs with an encapsulated iron(II) ion. The hexathiophenol... 

Beck and co-workers (84,8.5) utilized the anionic carbonylmetallates [M(C0)5] (M = Mn, Re) and [WCp(CO),] in nucleophilic addition reactions with cationic hexadienyl, cyclohexadienyl, cycloheptadienyl, and cyclooctadienyl complexes of iron and ruthenium to give heterobimetal lie complexes with rj iV-hydrocarbon bridges. The reaction of [Fe(i7 -... 

Besides Selegue s methodology, several synthetic alternatives of ruthenium allenylidene complexes have been reported. The most popular involves trapping of transient butatrienylidene or pentatetraenylidene intermediates with nucleophiles [26-29]. Although alcohols, amines, or thiols have been usually employed in these reactions leading to the corresponding heteroatom-substituted allenylidenes, in some cases the use of carbon-centred nucleophiles, such as pyrroles, has been described [185, 186]. Quite recently, a systematic route to prepare sequentially polyalkenyl-allenylidene complexes has also been discovered (Scheme 11) [187— 189]. The first step consists of the insertion of the ynamine MeC=CNEt2 into the... 

Star-shaped molecules containing cationic arene complexes of iron and ruthenium have been reported by Astruc and co-workers.298 Utilizing the activating nature of the cyclopentadienyliron moiety on the complexed arene, 260 was converted into 262 via bromobenzylation. The photolysis of 262 gave 263, which was subsequently reacted with 264 to give the hexametallic complex 265. Further nucleophilic aromatic substitution reactions with phenol 266 gave the allyl-substituted complex 267 (Scheme 2.70). 

Sharpless and Kim reported a one-pot synthesis of cyclic sulfates 96 from 1,2-diols via catalytic oxidation with ruthenium chloride51. The cyclic sulfates 96 thus formed on treatment with nucleophiles give /2-sulfates 97, which in turn are hydrolyzed to the / -hydroxy compounds 98 (equation 54). Hence the cyclic sulfates 96 are synthetically equivalent to epoxides. The results of ring opening of cyclic sulfates 96 are shown in Table 4. When the reaction of 99 with malonate anion is carried out in DME, the /2-sulfate moiety serves as a leaving group to give cyclopropane 100 (equation 55)51. 

Aryne complexes of late transition metals are very reactive towards both nucleophiles (amines, alcohols, water) and electrophiles (iodine). They also undergo insertion reactions with CO, alkenes and alkynes,but while the behaviour of ruthenium complexes is somewhat similar to that of titanium or zirconium complexes, the reactivity of nickel complexes is rather different [6,8]. Examples of these reactions that are particularly interesting for the purposes of this chapter are shown in Schemes 8 and 9. Ruthenium complex 33 undergoes insertion of a molecule of benzonitrile,benzaldehyde or di(p-tolyl)acetylene to yield met-allacycles 40,41 and 42, respectively (Scheme 8). Further insertion of a second unsaturated molecule into these metallacycles has not been observed [25,27]. 

Ruthenium complexes attract recent interest as new promising candidates for efficient, specific and environmentally benign allylation catalysts. It is noticeable that some J7 -allylruthenium(II) complexes have an ambiphilic property in catalysis involving the C-0 bond activation [52]. When allyl carboxylates or carbonates are treated with nucleophilic 1,3-dicarboxylates or electrophilic aldehyde in the presence of Ru complexes, catalytic allylations of nucleophiles or electrophiles take place [53]. In both reactions, J7 -allylruthenium complexes are assumed to be intermediates. Independent synthesis and reactions of the model compounds support this observation (Scheme 3.28). This ambiphilicity of the allylruthenium(II) may arise from the different reactivity of and rf forms in the allylic moiety [54]. 

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