Ru- p-cymene TsDPEN

10 SELECTIVE REDUCTION OF CARBONYL GROUP IN p,y-UNSATURATED a-KETOESTERS BY TRANSFER HYDROGENATION WITH Ru(P-CYMENE)(TsDPEN) 

The transfer hydrogenation of a-keto- S -unsaturated esters, catalyzed by Ru(p-cymene)(TsDPEN) (TsDPEN monotosylated l,2-diphenylethylene-l,2-dia-mine) with 2-propanol as the hydrogen source, has been developed as an efficient method for the preparation of a-hydroxy-)S, y-unsaturated esters or acids. 

1 SYNTHESIS OE Dl-/i-CHLORO-BlS[CHLORO(f -l-lSOPROPYL-4-METHYL-BENZENE)RUTHENlUM(ll)]  

Under the argon atmosphere, a solution of hydrated ruthenium trichloride (approximately RuCl3 3H20, containing 38-39% Ru) (1.00 g, approximately 3.83 mmol) in 50 mL of ethanol was treated with 5 mL of y-terpinene and heated under reflux in a 100-mL, round-bottomed flask for 4h. The hot solution was filtered as quickly as possible to remove the undissolved dark residue. The filtrate was concentrated to 25 mL under reduced pressure and cooled to room temperature and the red-brown microcrystalline product that resulted was collected by filtration. After drying in vacuo (approximately 1 mmHg) for 4 h, 0.70 g (59.9 %) of ruthenium complex was obtained. 

2 SYNTHESIS OF ( )-MONOTOSYLATE-l,2-DlPHENYL-l,2-ETHYT. ENEDl AMTNEJ J 

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A mixrnre of [RuCl2( -p-cymene)]2 (306 mg, 0.5 mmol), TsDPEN (366 mg, 1.0 mmol) and KOH (400 mg, 7.1 mmol) in 7 mL dichloromethane was stirred at room temperature for 5 min. On addition of water (7 mL) to the reaction mixmre, the colour changed from orange to deep purple. The purple organic layer was washed with 5 mL of water, dried with calcium hydride and concentrated to dryness to give the deep purple complex Ru(p-cymene)(TsDPEN) (455 mg, 75.8 % yield). 

A degassed Schlenk reaction tube was charged successively with the ketoester (0.5 mmol), isopropyl alcohol (5mL) under argon atmosphere. The reaction mixture was degassed three times by the circulation of freeze-pump-thaw, then Ru(p-cymene)(TsDPEN) (3 mg, 0.005 mmol) was added under argon atmosphere. The reaction mixture was then stirred at argon atmosphere for about 1 h to effect a complete conversion of the substrate. The solvent was removed... 

In conclusion, we have found a convenient and practical method for the selective reduction of C=0 bond of a wide spectrum of a-keto-)S, -unsaturated esters with Ru(p-cymene)(TsDPEN) as catalyst. The transition metal catalyzed transfer hydrogenation reaction with good selectivity and high efficiency offers possibilities to provide the optically active a-hydroxy-/l, y-unsaturated esters with chiral catalysts. Table 3.8 gives different substrates that can be reduced with Ru(p-cymene) (TsDPEN) complex in isopropyl alcohol. 

The reaction process can be monitored by TLC or GC. The unsaturated ketoester is generally consumed within 1 h. Once the starting material is consumed, the reaction can be quenched with 1 N HCl. The double bond in the product will be slowly reduced at elevated temperature (80 °C) and prolonged reaction time. However, it is relatively stable at room temperature under the catalysis of Ru(p-cymene)(TsDPEN) no significant amount (<1 %) of double bond reduced product was detected 5h after the consumption of the starting material. 

The asymmetric synthesis of allenes via enantioselective hydrogenation of ketones with ruthenium(II) catalyst was reported by Malacria and co-workers (Scheme 4.11) [15, 16]. The ketone 46 was hydrogenated in the presence of iPrOH, KOH and 5 mol% of a chiral ruthenium catalyst, prepared from [(p-cymene) RuC12]2 and (S,S)-TsDPEN (2 equiv./Ru), to afford 47 in 75% yield with 95% ee. The alcohol 47 was converted into the corresponding chiral allene 48 (>95% ee) by the reaction of the corresponding mesylate with MeCu(CN)MgBr. A phosphine oxide derivative of the allenediyne 48 was proved to be a substrate for a cobalt-mediated [2 + 2+ 2] cycloaddition. 

Conditions Ru cat = RuCI[(S, S)-Tsdpen](p-cymene), HCOOH/N(C2H5)3 = 4.4/2. Fig. 5 Asymmetric reduction of imsymmetrically substituted 1.2-diketone... 

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