Ruthenium Lewis Acid-Catalyzed Reactions

Lewis acids play key roles in a large number of reactions, and their use in organic synthesis continues to see rapid development, particularly in the field of asymmetric catalysis [1], Late transition metal Lewis acid catalysts have emerged as a new class of compounds within this area. They offer neutral and mild conditions that are of interest for the needs of modern chemistry and its focus on economically and ecologically friendly methods. 

In comparison with classic Lewis acids derived from main group halides (e.g., B, Al, Sn), f-elements, and early transition metal halides, late transition metal Lewis acids often are more inert to ubiquitous impurities such as water, offer higher stability, tunable properties by ligand modification, and a well-defined structure and coordination chemistry, thus allowing detailed studies of reaction mechanisms, and a rational basis for catalyst optimization. Among this new class of late transition metal Lewis acids, ruthenium complexes - the subject of this chapter - display remarkable properties 

This review of Ru-based Lewis acids centers on in-situ procedures in which the metal activates a substrate by forming a n-bond to a Lewis basic atom of the reacting substrate. Particular attention will be paid to stereoselective and catalytic reactions. We exclude from this survey the vast area of chemistry of transition metal complexes of jt-bound unsaturated ligands, as details of these are described in other chapters of this book. 

Ethers, Acetals, Carboxylic Acid Derivatives, and Epoxides 

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Viton F, Bemardinelli G, Kiindig EP (2002) Iron and ruthenium Lewis acid catalyzed asymmetric 1,3-dipolar cycloaddition reactions between nitrones and enals. J Am Chem Soc 124 4968-4969... 

Mascarenas developed a synthetic method to 1,5-oxygen-bridged medium-sized carbocycles through a sequential ruthenium-catalyzed alkyne-alkene coupling and a Lewis-acid-catalyzed Prins-type reaction (Eq. 3.45). The ruthenium-catalyzed reaction can be carried out in aqueous media (DMF/H20 = 10 1).181... 

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 importance of fluorinated organic componnds both in medicinal chemistry and biochemistry has resulted in much recent attention towards efficient carbon fluorine bond formation [30]. The reactions developed include a very successful electrophilic asymmetric mono-fluormation of 1,3-dicarbonyl compounds [31]. A nucleophilic variant was also investigated. In this context, the groups of Togni and Mezzetti have established that ruthenium Lewis acids could efficiently catalyze fluorination reactions [32]. In the presence of [Ru(l,2-bis(diphenylphosphino)ethane)2Cl][PF6] (8) (10 mol%), fert-butyl iodide reacted at room temperature with TIF (1.1 equiv.) to yield fert-butyl fluoride (84% yield). This reaction was extended successfully to a range of organic halides (Entries 1-3, Scheme 10.19). The use of the chiral complex [Ru((lS,2S)-N,N bis[2-diphenylphos-phino)benzylidene]diaminocydohexane))Cl][PF6] (9) showed modest chiral induction at the outset of the reaction (Entry 4, Scheme 10.17). The near-racemic mixture obtained at completion points to an SNl-type process in this nucleophilic halide... 

While copper and iron Lewis acids are the most prominent late transition metal Diels-Alder catalysts, there are reports on the use of other chiral complexes derived from ruthenium [97,98],rhodium [99],andzinc [100] in enantioselective cycloaddition reactions, with variable levels of success. As a comparison study, the reactions of a zinc(II)-bis(oxazoline) catalyst 41 and zinc(II)-pyridylbis(ox-azoline) catalyst 42 were evaluated side-by-side with their copper(II) counterparts (Scheme 34) [101]. The study concluded that zinc(II) Lewis acids catalyzed a few cycloadditions selectively, but, in contrast to the [Cu(f-Bubox)](SbFg)2 complex 31b (Sect. 3.2.1), enantioselectivity was not maintained over a range of temperatures or substitution patterns on the dienophile. An X-ray crystal structure of [Zn(Ph-box)] (01)2 revealed a tetrahedral metal center the absolute stereochemistry of the adduct was consistent with the reaction from that geometry and opposite that obtained with Cu(II) complex 31. 

Studies of ruthenium-catalyzed reactions in carboxylic acid solvents have been reported by Knifton (171,172), but most of these experiments contain added salt promoters which greatly modify the catalytic behavior. These experiments will be considered in Section V, along with other Lewis base-promoted ruthenium systems. 

Solid-phase synthesis is of importance in combinatorial chemistry. As already mentioned RuH2(PPh3)4 catalyst can be used as an alternative to the conventional Lewis acid or base catalyst. When one uses polymer-supported cyanoacetate 37, which can be readily obtained from the commercially available polystyrene Wang resin and cyanoacetic acid, the ruthenium-catalyzed Knoevenagel and Michael reactions can be performed successively [27]. The effectiveness of this reaction is demonstrated by the sequential four-component reaction on solid phase as shown in Scheme 11 [27]. The ruthenium-catalyzed condensation of 37 with propanal and subsequent addition of diethyl malonate and methyl vinyl ketone in TH F at 50 °C gave the adduct 40 diastereoselectively in 40 % yield (de= 90 10). 

It was recently shown by Zhang and coworkers that Ru(PPh3)3Cl2 is a suitable catalyst for the alkylative coupling of tertiary alcohols 186 to primary alcohols 185 leading to branched alcohols 187 in 32-98% yield (Fig. 46) [258]. The reaction required the presence of a Lewis acid, such as BF3 OEt2. It mediates the dehydration of the tertiary alcohol to a 1,1-disubstituted alkene, which coordinates the ruthenium catalyst. The further course is likely to be similar to the corresponding iron- or rhodium-catalyzed reactions (see Sects. 2.8 and 6). 

The moderate Lewis acidity of ruthenium complexes was used to promote catalytic Diels-Alder reaction of dienes and acrolein derivatives [21-23]. The enantioselective Diels-Alder reaction of methacrolein with dienes was catalyzed with cationic ruthenium complexes containing an arene or cyclo-pentadienyl (Cp) ligand and a chiral ligand such as phosphinooxazoline, pyridyl-oxazoline, monoxidized 2,2 -bis(diphenylphosphino)-1, T-binaphthyl (BINPO)or l,2-bis[bis(pentafluorophenyl)phosphanyloxy]-l,2-diphenylethane (BIPHOP-F). The reaction gave the cycloadduct in high yields with excellent... 

Copper(I) triflate was used as a co-catalyst in a palladium-catalyzed carbonylation reaction (Sch. 27). The copper Lewis acid was required for the transformation of homoallylic alcohol 118 to lactone 119. It was suggested that the CuOTf removes chloride from the organopalladium intermediate to effect olefin complexation and subsequent migratory insertion [60]. Copper(I) and copper(II) chlorides activate ruthenium alkylidene complexes for olefin metathesis by facilitating decomplexation of phosphines from the transition metal [61]. 

The ruthenium-cobalt bimetallic complex system catalyzes the homologation of methanol with carbon dioxide and hydrogen in the presence of iodide salts. A synergistic effect is found between these two metals. The yield of ethanol is also affected by the Lewis acidity of the iodide salt, lithium iodide being most effective. The reaction profile shows that methanol is homologated with CO formed by the hydrogenation of CO2. 

An even better nucleophile is nitrogen. The incompatibility of basic amines for almost every one of these reactions catalyzed by these coordinatively unsaturated Ru complexes led us to examine sulfonamides and carboxamides. However, no productive results ensued. A basic amino group was also examined to verify its incompatibility. In contrast to that expectation, cyclization proceeded without problems as summarized in Equation 1.70 [61]. A Lewis acid was required as a cocatalyst. For formation of pyrrolidines, titanium tetrachloride proved most efficacious whereas for formation of piperidines, methylaluminum dichloride proved best. In principle, any nucleophile, such as carbon, that satisfactorily reacts in ruthenium-catalyzed allylic alkylations should function here also. 

The system is quite similar to the Pd-Py-Lewis acid catalysts above described. However while palladium in the presence o f a large excess o f pyridine alone is totally inactive in this reaction, palladium in the presence of 3,4,7,8-tetramethylphenantroline is able to catalyze the carbonylation of PhN02 to PhNHC02Et at 180 C and 40 atm (42.5 conversion and 51.5 < selectivity) when 2,4,6-trimethylbenzoic acid was also added to the catalytic system in a 8 to 1 ratio with palladium, the conversion reached lOOX, with more than 95X sel ect i v i ty [252]. Metals such as ruthenium, rhodium and platinum were much less active and selective under the same experimental conditions. 

Besides various iron and ruthenium complexes [43, 44], nickel-based catalysts have recently been shown to be highly reactive in this respect as well [45]. Thus, a nickel catalyst prepared in situ from equimolar amounts of NiCl2(dppe) (dppe, l,2-bis(diphenylphosphino)ethane) and LiBHEtj (5 mol% each), which presumably resulted in the formation of NiHCl(dppe) as the active catalyst, efficiently catalyzed the isomerization/aldol event of allyl alcohols 82 and aldehydes 83 in combination with the Lewis acid MgBr2 (5 mol%) to furnish aldol products 84 in typically excellent yields and variable isomeric ratios (Table 8.11). Allyl alcohols with a terminal alkene reacted much faster than those with an internal olefin, and the aldol reaction occurred exclusively on the side of the former allyl alcohol. 

Group 8 Iron and Ruthenium. Iron is the second most abundant metal in the earth crust (4.7%) and iron compoimds are relatively nontoxic and very cheap and efficient Lewis acid catalysts that recently has been attracted much attention in a great deal of useful organic transformations. Since 1979 (39), iron-catalyzed aldol reactions have been studied extensively (40). Iron porphyrin (41), (bda)Fe(CO)3 and (COT)Fe(CO)3 (42), and FeCla (43,44) were fovmd to be... 

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