Hydrogenation of P-ketoester

The seven-membered ring containing chiral bisphosphine 121 (n = 1) was made as part of a series of bisphosphines (n = 1-6) to study the influence of ligand dihedral angles on the enantioselectivity of Ru-catalysed asymmetric hydrogenation of p-ketoesters . 

The previous volume of Organic Syntheses provides a detailed procedure for the asymmetric hydrogenation of p-ketoesters using a BINAP-ruthenium complex.15... 

Enantioselective hydrogenation of p-ketoesters with monodentate ligands. Angew, Chem., Int. Ed., 43, 5066-5096. 

Functionalized P-hydroxy esters 64 e,f,g,h were obtained quantitatively with excellent enantiomeric excesses (> 98 %) by hydrogenation of p-ketoesters in the presence of chiral ruthenium catalysts. This convenient methodology gives both optical antipodes with equal ease using (/ ) or (5) atropoisomer ligand for the metal complex. 

The first transition metal catalysis using BINAP-ruthenium complex in homogeneous phase for enantioselective hydrogenation of P-ketoesters was developed by Noyori and co-workers [31]. Genet and co-workers described a general synthesis of chiral diphosphine ruthenium(II) catalysts from commercially available (COD)Ru(2-methylallyl)2 [32]. These complexes preformed or prepared in situ have been found to be very efficient homogeneous catalysts for asymmetric hydrogenation of various substrates such as P-ketoesters at atmospheric pressure and at room temperature [33]. 

When we commenced our studies in 1995, perhaps the most intriguing aspect of the literature on the enantioselective hydrogenation of P-ketoesters over supported Ni catalysts was the critical dependence between enantiomeric excesses obtained and system variables such as temperature, concentration of modifier, time of modification, pH, etc [6, 7]. The underlying cause of this behaviour became evident when we discovered that the adsorption behaviour of enantiopure (7 ,J )-tartaric acid... 

In this section, we focus on the Ni(llO) surface, the metal most commonly modified by tartaric acid, to yield the successful enantioselective catalytic system for the hydrogenation of P-ketoesters [6, 7], A detailed study [22, 23] of the adsorption of (/ ,/ )-tartaric acid on Ni(llO) as a function of temperature and coverage again shows a polymorphic system, (Fig. 5.8) with the local nature of the chiral adsorbate changing dynamically as conditions change, echoing the findings on Cu(llO). 

Scheme 10.8 Quantitative analysis of the product ee-values obtained by the hydrogenation of P-ketoesters over the tartaric acid-NaBr-modified Raney nickel. Factor-/ indicates the intrinsic enantioselective ability of the tartaric acid-modified sites, and E and N indicate the contribution of the enantioselective catalysis sites and nonenantioselective hydrogenation sites, respectively.

The tartaric acid-NaBr-modified nickel catalyst is one of the intensively studied enantio-differentiating solid catalysts. This catalyst has a high enantio-differentiating ability (e.d.a.) for the hydrogenation of p-ketoesters and 2-alkanones [1-7]. E.d.a. values of 80-98% were attained for the hydrogenation of various P-ketoesters and 72-85% for that of the 2-afkanones. The tartaric acid-NaBr-modified nickel catalyst can be prepared by two methods, one is a conventional pre-modification method [2, 8-13], and the other is an in-situ-... 

Pyridines have also been constructed as essential portion of ligands used for transition metal catalysis. Chan and co-workers report the synthesis of dipyridylphosphines as ligands for the Ru-catalyzed asymmetric hydrogenation of p-ketoesters <01SL1050>. Pallet and coworkers report on the synthesis and use of a Ruthenium (R)-QUINAP catalyst for use in enantioselective Diels-Alder reactions <01OM2454>. 

Enantioselective hydrogenation of P-ketoesters has been achieved by using a ruthenium catalyst derived from (R,R)-l,2-bis(trans-2,5-diisopropylphospholano)ethane [(R,R)-i-Pr-PPE-Ru] to give P-hydroxy esters with high conversion and high ee under mild conditions (Scheme 103). "... 

Pye PJ, Rossen K, Reamer RA, Volante RP, Reider PJ. [2.2] PHANEPHOS-Ruthenium(II) complexes highly active asymmetric catalysts for the hydrogenation of p-ketoesters. Tetrahedron Lett. 1998 39(25) 4441 t444. 

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