Ruthenium methyl ketone synthesis

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). 

Enyne RCM reactions have been successfully coupled with a CM event [16]. Thus, a domino enyne RCM/CM process with enyne 65 and methyl vinyl ketone was used as the final step in a concise total synthesis of the bioactive sesquiterpene lactone (+)-8-epi-xanthatin (66) (Scheme 2.25) [16a,b. Using the phosphine-free ruthenium catalyst 4, an efHcient transformation was achieved with the required electron-deficient co-olefin. 

The installation of the butyrolactone substituent at C3 started with the addition of the lithiated form of the ortho ester 121 to 120. The y-butyrolactone core was installed after stereoselective reduction of the ketone moiety and exposure to TsOH in methanol. Claisen rearrangement afforded 122 which resisted attempts to undergo iodocyclization, but afforded tetracylic 123 after selenolactonization followed by Keck allylation and a-methylation. The total synthesis of (—)-tuberostemonine (4) was concluded after 25 steps and in 1.7% overall yield from 113 after isomerization of the allyl group and cross-metathesis with ethylene promoted by ruthenium catalyst 117 to provide the terminal vinyl group which was stereoselectively hydrogenated. 

Conjugated dienes can be selectively hydrated to ketones in the presence of cationic ruthenium complexes with bipyridyl ligands. The role of ruthenium is to catalyze the isomerization of allylic alcohols formed by the addition of water to diene. This method allows one to convert butadiene to methyl ethyl ketone in high yield [187]. Hydration of triple bonds is one of the oldest catalytic processes of organic chemistry. Though this reaction has no industrial value, it can serve as a tool of fine organic synthesis. The hydration can be catalyzed by rhodium salts under phase-transfer conditions [188]. The more exotic process of the hydrolysis of phenylacetylene to toluene and carbon monoxide catalyzed by ruthenium complex should also be mentioned [189] ... 

Jenner, G. Bentaleb, A. (1994) Ruthenium-catalyzed ethylene-methyl formate reactions synthesis of propanol and ketones, J. Mol Catal,91, 31-43. 

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