Alkyne ruthenium-catalyzed reactions

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... 

Much less information is available about [2 + 2]-cycloadditions. These allow the formation of cyclobutane derivatives in the reaction between two alkenes, or that of cyclobutenes from alkenes and alkynes. The reaction can be achieved thermally via biradical intermediates,543 by photoreaction,544 and there are also examples for transition-metal-catalyzed transformations. An excellent example is a ruthenium-catalyzed reaction between norbomenes and alkynes to form cyclobutenes with exo structure ... 

Considerable effort has been devoted to achieving the intermolecular catalytic Pauson-Khand reaction. The mthenium complex-catalyzed reaction of an alkyne with an alkene such as ethylene or 2-norbornene under CO gave hydroquinone derivatives [79], with CO (2 mol) being introduced into the products (Eq. 11.36). This reaction is the first example of the preparation of hydroquinone derivatives by the reaction of alkynes and alkenes with CO, while hydroquinone is synthesized by the ruthenium-catalyzed reaction of 2 mol acetylene with 2 mol CO (Eq. 11.37) [80]. 

The significance of ruthenium-catalyzed reactions is also emphasized by a publication by Mitsudo et al., [16] who achieved [2+2]cycloadditions of norbomene 29 and norbomadiene 32 with a range of alkynes 30. These reactions are catalyzed by chloroC " -cyclooctadiene)(77 -pentamethylcyclopenta-dienyl)ruthenium(II) [Cp Ru(COD)Cl] (35) and give 31 and 33, respectively, in good yields (Scheme 10). 

The ruthenium-catalyzed reaction of unsymmetrically substituted internal alkynes affords mixtures of the stereoisomers 29 and 30 °. 

In addition to ruthenium-catalyzed reactions, a range of other transition metal catalysts have shown activity toward the addition reaction. A series of air-stable gold compounds promoted the addition of carboxylic acids to alkynes (Scheme 2.93) [138]. A variety of gold and silver compounds were screened as catalysts for the reaction, and the most effective pair under the mildest conditions was (Ph3P)AuCl and AgPF. Under the reactions conditions, the reaction was highly selective for the formation of the Markovnikov addition product, and minimal or none of the anti-Markovnikov products were observed. 

Functionahzed indoles were prepared in high yield through a ruthenium-catalyzed reaction between aryl azides and terminal alkynes (Scheme 3.63) [69]. The results of this reaction were in stark contrast to the normal reactivity of organoazides with alkynes that generated triazoles. The change in the direction of the reaction was proposed to be due to the presence of powerful electron-withdrawing groups on the aryl azide. 

Cycloaromatization of enediynes by diradical pathways in the thermal-and metal-catalyzed routes allows nonfunctionalized benzene derivatives to be prepared. The aromatization of enediynes by the action of nucleophiles produces aromatic compounds retaining the respective nucleophilic residue [333, 334]. The ruthenium-catalyzed reaction gives rise to the synthesis of various functionalized benzene derivatives. Thus, adding water, alcohols, aniline, acetylacetone, pyrroles, and dimethyl malonate to acyclic and aromatic enediynes 3.711 at 100°C for 12-24 hours in the presence of TpRuPPh3(MeCN)2PF6 (10 mol%) led to the functionalized benzenes 3.712 in satisfactory yields (Scheme 3.79) [334]. This cyclization involves regioselective nucleophilic attack of enediyne 3.711 to form a, TT-vinylruthenium intermediate 3.714 which finally converts to the benzene derivative. Experiment with labeled hydrogen atoms showed that the ruthenium n-alkyne complexes 3.713 are catalytically active. 

In addition to the reactions discussed above, there are still other alkyne reactions carried out in aqueous media. Examples include the Pseudomonas cepacia lipase-catalyzed hydrolysis of propargylic acetate in an acetone-water solvent system,137 the ruthenium-catalyzed cycloisomerization-oxidation of propargyl alcohols in DMF-water,138 an intramolecular allylindination of terminal alkyne in THF-water,139 and alkyne polymerization catalyzed by late-transition metals.140... 

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). 

Scheme 12 Ruthenium-catalyzed hetero Pauson-Khand reactions with alkynes and al-lenes...

Recently, cyclopropane derivatives were produced by a ruthenium-catalyzed cyclopropanation of alkenes using propargylic carboxylates as precursors of vinylcarbenoids [51] (Eq. 38). The key intermediate of this reaction is a vinylcarbene complex generated by nucleophilic attack of the carboxylate to an internal carbon of alkyne activated by the ruthenium complex. Then, a [2+1] cycloaddition between alkenes and carbenoid species affords vinylcyclo-propanes. 

The C-C bond formation can also be obtained via a first-step addition of a heteroatom to alkynes. Thus, the reaction of the three components terminal alkyne, water and enone led to 1,5-diketone with atom economy, using the system CpRuCl(COD)/NH4PF6 and In(0S02CF3)3 as a cocatalyst [58,59] (Eq. 43). The mechanism is postulated to proceed by the ruthenium-catalyzed nucleophilic addition of water to alkynes to generate a ruthenium enolate intermediate allowing further insertion of enone and formation of 1,5-diketones after protonation. 

Finally, ruthenium-catalyzed carbocyclization by intramolecular reaction of allylsilanes and allylstannanes with alkynes also led to the formation of vinyl-alkylidenecyclopentanes [81] (Eq. 60). This reaction is catalyzed by RuC13 or CpRuCl(PPh3)2/NH4PF6 in methanol. The postulated mechanism involves the coordination of the alkyne on the ruthenium center to form an electrophilic /f-alkyne complex. This complex can thus promote the nucleophilic addition of the allylsilane or stannane double bond. 

Selective addition of alkenes and alkynes to aromatic compounds has also been performed by ruthenium-catalyzed aromatic C-H bond activation. Carbon-carbon bond formation occurs at the ortho positions of aromatic compounds, assisted by the neighboring functional group chelation. The reaction, catalyzed by RuH2(CO)(PPh3)3, was efficient with aromatic and heteroaromatic compounds, with various functional groups, and a variety of alkenes and alkynes [ 121 ] (Eq. 90). Activation of vinylic C-H bonds can occur in a similar manner. 

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