Ruthenacycles

In aqueous media, the addition of unactivated alkynes to unactivated alkenes to form Alder-ene products has been realized by using a ruthenium catalyst (Eq. 3.44).180 A polar medium (DMF H20 = 1 1) favors the reaction and benefits the selectivity. The reaction was proposed to proceed via a ruthenacycle intermediate. 

A ruthenium dihydrogen complex G or a ruthenacycle D, which was proposed as a potential intermediate, catalyzed the insertion of ethylene into sp2-C-H bonds, with TONs reaching 19 after 48 h of reaction and under very mild conditions (room temperature as opposed to the usual 135 °C) (Equation (96)).91,91a91c... 

Cycloadditions on a ruthenium(n) complex between 2 equiv. of phenylacetylene and various types of isonitriles were described for the first time by Singleton.367 3673 These transformations were shown to proceed through coordinatively unsaturated ruthenacycle intermediates to furnish the corresponding imino-2,5-diphenylcyclopentadiene complexes. 

Based on this work, Itoh and co-workers developed ruthenium(n)-catalyzed [2 + 2 + 2]-cyclotrimerizations of 1,6-diynes 174 and electron-deficient nitriles (Equation (34)),368>368a These partially intramolecular cycloadditions proceed through ruthenacycle intermediates as well. The importance of using electronically activated nitriles is underlined by the fact that acetonitrile and benzonitrile gave only very low yields. 

Trost and others have extensively studied the ruthenium-catalyzed intermolecular Alder-ene reaction (see Section 10.12.3) however, conditions developed for the intermolecular coupling of alkenes and alkynes failed to lead to intramolecular cycloisomerization due the sensitivity of the [CpRu(cod)Cl] catalyst system to substitution patterns on the alkene.51 Trost and Toste instead found success using cationic [CpRu(MeCN)3]PF6 41. In contrast to the analogous palladium conditions, this catalyst gives exclusively 1,4-diene cycloisomerization products. The absence of 1,3-dienes supports the suggestion that the ruthenium-catalyzed cycloisomerization of enynes proceeds through a ruthenacycle intermediate (Scheme 11). 

PfefFer, de Vries and coworkers developed the use of ruthenacycles, based on chiral aromatic amines as enantioselective transfer hydrogenation catalysts. These authors were able to develop an automated protocol to produce these catalysts by reacting ligand and metal precursor in the presence of base, KPFS in CH3CN. After removal of the solvent, isopropanol was added followed by the substrate, acetophenone, and KOtBu. In this way, a library of eight chiral... 

Scheme 36.7 Parallel ruthenacycle preparation and screening in asymmetric transfer hydrogenation.

The Ru-catalyzed cyclocarbonylation of a-allenic sulfonamides proceeds in the presence of Et3N under a CO atmosphere (20 atm) to yield ,/funsaturated lactams (Scheme 16.32) [36], In order to gain an insight into the reaction mechanism, a deuterium-substituted a-allenic sulfonamide was subjected to the carbonylation. The deuterium was found to be totally transferred to the methyl group. Based on this observation, a mechanism has been proposed which involves a ruthenacycle derived from addition of the Ru-H to the terminal double bond of allene (Scheme 16.33). 

A related intramolecular coupling between a monodentate acetate ligand and a transient diphenylallenyhdene moiety was observed when the hydroxo-alkynyl derivative 78 was treated with HPFg, affording the ruthenacycle 79 (Scheme 27) [283],... 

Thus, the [Ru(phpy)(phen)2]+ ruthenacycle is a strikingly reactive electron donor for HRR High rate constants for other complexes are summarized in Table IX. Plant peroxidases from sources other than horseradish also show a high reactivity to cyclometalated ruthenium(II) complexes listed in Table IX (234). 

Dimcthyl 2-(but-2-ynyl)-2-(5-oxopent-3-enyl)malonates 96 undergo ruthenium-catalyzed intramolecular cycli-zations to yield cyclohexyl fused 4//-pyrans 97, most likely via formation of and reductive elimination from the ruthenacycle intermediate 98 (Scheme 32). Likewise, internal alkynes tethered to an a, 3-unsaturated ketone via a three-component chain undergo mthenium-catalyzed cyclizations furnishing 4//-pyrans that are fused to five-membered rings 99 (Equation 50) <2000JA5877>. 

Functional 1,5-dienes were also synthesized in good yields by ruthenium-catalyzed regioselective codimerization of enol esters with 2-substituted-l,3-bu-tadienes [20] (Eq. 16). A ruthenacycle intermediate formed by oxidative coupling was proposed followed by intracyclic /1-hydride elimination. The (Z)-selectivity is thought to result from the configurational inhibition for the /1-hydride elimination in the intermediate ruthenacyclopentane. 

A ruthenacyclopentane 48 has been proposed as an intermediate in this reaction, after coordination of the allene and enone. Exocyclic /1-hydride elimination led to the 1,3-dienes. This ruthenacycle possessed a o-bound ruthenium allyl, allowing nucleophilic additions by alcohols or amines. Alkylative cycloetherification [29] (Eq. 20) and synthesis of pyrrolidine and piperidine [30] were thus achieved. 

The presence of two different isomers can be viewed through the competitive ruthenacycle formation, depending on the orientation of the alkyne via oxidative coupling. A /3-hydride elimination, which is favored with H exocyclic with respect to intracyclic /3-hydride, produces the 1,4-dienes (Scheme 2). 

The coupling between alkenes and alkynes can also afford cyclization reactions and leads to strained carbocycles. Most of these reactions are performed via a ruthenacycle intermediate leading to [2+2] cycloaddition. 

One of the first examples of ruthenium-catalyzed C-C bond formation afforded the synthesis of cyclobutenes, from norbornene derivatives with dimethyl acetylenedicarboxylate, and was reported by Mitsudo and coworkers [45, 46] by using various catalysts such as RuH2(CO)[P(p-C6H4F)3]3 or RuH2(PPh3)4. More recently, the complex Cp RuCl(COD) has shown to be an excellent catalyst for the [2+2] cycloaddition of norbornenes with various internal alkynes [45] (Eq. 33) and with a variety of substituted norbornenes and norbornadienes [47]. The ruthenacycle intermediate, formed by oxidative coupling, cannot undergo /1-hydride elimination and leads to cyclobutene via a reductive elimination. 

In both cases, a ruthenacycle intermediate cannot be ruled out. Furthermore, an intramolecular version from yne-enones was carried out and the formation of the products seemed to involve a ruthenacycle intermediate (see Eq. 56). 

Besides enyne metathesis [66] (see also the chapter Recent Advances in Alkenes Metathesis in this volume), which generally produces 1-vinylcyclo-alkenes, ruthenium-catalyzed enyne cycloisomerization can proceed by two major pathways via hydrometallation or a ruthenacycle intermediate. The RuClH(CO)(PPh3)3 complex catalyzed the cyclization of 1,5- and 1,6-enynes with an electron-withdrawing group on the alkene to give cyclized 1,3-dienes, dialkylidenecyclopentanes (for n=2), or alkylidenecyclopentenes (for n= 1) [69,70] (Eq. 51). Hydroruthenation of the alkyne can give two vinylruthenium complexes which can undergo intramolecular alkene insertion into the Ru-C bond. 

When the double bond of the enyne possesses a cyclopropyl substituent, an intramolecular [5+2] cycloaddition of alkyne and vinylcyclopropane takes place [75, 76]. The ruthenacycle does not undergo /l-hydride elimination but a rearrangement of the cyclopropane to produce a ruthenacyclooctadiene. Thus, a variety of bicyclic and tricyclic cycloheptadienes were obtained in good yields [75] (Eq. 55). 

The precatalyst Cp RuCl(COD) allowed the head-to-head oxidative dimerization of terminal alkynes and the concomitant 1,4-addition of carboxylic acid to stereoselectively afford 1-acyloxy-l,3-dienes in one step under mild conditions [89] (Eqs. 67,68). The first step of the reaction consists in the oxidative head-to-head alkyne coupling via the formation of a ruthenacycle intermediate that behaves as a mixed Fischer-Schrock-type biscarbene ruthenium complex, allowing protonation and nucleophilic addition of the carboxylate. 

Very recently, a new strategy for the hydroesterification and hydroamidation of olefins was reported by Chang and coworkers [83]. They used a chelation-assisted protocol for the hydroesterification of olefins. The reaction of 2-pyridylmethyl formate with 1-hexene in the presence of a Ru3(CO)12 catalyst gave the hydroesterification product in 98% yield as a mixture of linear and branched isomers (Eq. 54). The chain length of the methylene tether is important for a successful reaction. Thus, the reaction of 2-pyridyl formate (n=0) afforded 2-hydroxypyridine, a decarbonylation product, and the reaction of 2-pyridiylethyl formate (n=2) resulted in a low conversion (7% conversion) of the starting formate. From these results, the formation of a six-membered ruthenacycle intermediate is crucial for this chelation-assisted hydroesterification. 

Interestingly, however, in the case of the reaction of formamide, N-(2-pyridyl)formamide showed a high reactivity [84]. This result indicates that the reaction proceeds through a five-membered ruthenacycle intermediate. The olefins having a bulky substituent, such as ferf-butyl and trimethylsilyl groups, exhibited a high regioselectivity. 

The four main types of complex obtained from 325 and alkynes are illustrated in Scheme 63.540-542 Rather than insertion into the =C-H bond, coupling of the C2 ligand with 1-alkynes gives 358 which contains a ruthenacycle which has an rj4-interaction with a second Ru atom, as found in the dimerization of alkynes on Ru3 clusters. The Ru5 cluster becomes flattened, as found in 352. Under CO, extrusion of an Ru(CO)w group... 

Carbon-Carbon Bond Formations via Ruthenacycle Intermediates... 

The above mthenium(II)-catalyzed intramolecular alkyne cyclotrimerizations probably proceeded via a ruthenacycle intermediate similar to the aforementioned ruthenacyclopentatriene complex 18 reported by Dinjus (see Scheme 4.5) [24]. This was confirmed by the isolation of a bicyclic ruthenacyde intermediate and its reaction with acetylene (Scheme 4.11) [25]. The stoichiometric reaction of 17 with the internal diyne 31 possessing phenyl terminal groups in CDCI3 at ambient temperature afforded the expected mthenacycle complex 32 in 51% yield as single crystals. X-ray analysis of 32 disdosed that its Ru-Ca bond distances of 1.995(3) and... 

In addition to isolation and characterization of the ruthenacycle complexes 18 or 32, the detailed reaction mechanism of the [2 + 2 + 2] cyclotrimerization of acetylene was analyzed by means of density functional calculations with the Becke s three-parameter hybrid density functional method (B3LYP) [25, 33]. As shown in Scheme 4.12, the acetylene cyclotrimerization is expected to proceed with formal insertion/reductive elimination mechanism. The acetylene insertion starts with the formal [2 + 2] cycloaddition of the ruthenacycle 35 and acetylene via 36 with almost no activation barrier, leading to the bicydic intermediate 37. The subsequent ring-... 

The formation of 44 is reminiscent of that of 37 from the ruthenacycle 35 and acetylene (Scheme 4.12). With the above acetylene cydotrimerization mechanism in mind, the cleavage of the central Ru-C bond in 44 is expected to give rise to the intermediate 46. This possibility was also examined by means of density functional calculations [25]. 

---