Hydrogenation of 3-ketoester

In the hydrogenation of /3-ketoesters, more than 80% of the enantio-differentiation was performed regardless of the type of alkyl residue in the acyl or ester moieties as shown in Tables XXVIII and XXIX, respectively (52a). When the hydrogenation of AA with (R,R)-TA-NaBr-MRNi had been stopped at the point of 70% conversion and the enantiomer-differentiation (see Section IV,B) was controlled, (R,R)-2,4-pentanediol 7 with 98% optical purity was obtained by a single distillation of the product (46). 

Some neutral rhodium catalysts with chiral ligands, such as MCCPM 9 (see Scheme 33.3) [20c], Cy,Cy-oxoProNOP 15, and Cp,Cp-IndoNOP 18, demonstrate excellent enantioselectivities and reactivities in the hydrogenation of a-ketoesters and ketoamides indeed, they compare well with ruthenium-based catalysts (Table 33.2). Togni et al. have successfully used the Josiphos 47 ligand for the hydrogenation of ethyl acetoacetate [27], while the use of MannOPs has led to somewhat high enantioselectivities [18]. 

The asymmetric hydrogenation with BisP RuBr2 may be applied to a wide range of (3-ketoesters, (3-kctoamidcs, and (3-ketophosphonates. Table 9.2 shows typical examples. 

The chapter Chiral Modification of Catalytic Surfaces [84] in Design of Heterogeneous Catalysts New Approaches based on Synthesis, Characterization and Modelling summarizes the fundamental research related to the chiral hydrogenation of a-ketoesters on cinchona-modified platinum catalysts and that of [3-ketoesters on tartaric acid-modified nickel catalysts. Emphasis is placed on the adsorption of chiral modifiers as well as on the interaction of the modifier and the organic reactant on catalytic surfaces. 

Cyclic 1,3-diketones can also participate in this MCR. Thus, utilization of two equivalents of 1,3-cyclohexanedione or dimedone instead of (3-ketoesters led to hydrogenated acridine derivatives. However, when only one equivalent of cyclic 1,3-dicarbonyl is used in combination with one equivalent of (3-ketoester, unsym-metric 1,4-DHPs may be obtained (Scheme 3). For example, this reaction was applied to the synthesis of ZD0947, a potassium chaimel opener [20]. 

Similar but smaller effects of hydrogen concentration were observed with other aromatic and alkyl-aromatic trifluoromethyl ketones such as 2 and 3 (Table 2). On the contrary, in the hydrogenation of the aliphatic ketone 4 medium to high hydrogen pressure favoured the enantiodifferentiation. Note that this correlation is typical for the hydrogenation of a-ketoesters and other activated ketones over the Pt-CD system4. 

Furthermore, these ruthenium(binap) complexes are remarkably effective catalysts for the hydrogenation of C=0 bond of 3-ketoesters giving optically active alcohols [175]. 

Salen palladium(II) complexes have been reported to be effective homogeneous, or when immobilized, to be active heterogeneous catalysts for the hydrogenation of alkenes [1,2]. It is also known that platinum(O) catalysts modified with cinchona alkaloids catalyze the enantioselective hydrogenation of a-ketoesters to the corresponding a-hydroxyesters[3]. The platinum(O) catalyst is attached to AI2O3 [4] or to zeolites [5,6]. 

Muzart and coworkers have succeeded in a catalytic asymmetric protonation of enol compounds generated by palladium-induced cleavage of 3-ketoesters or enol carbonates under nearly neutral conditions [47,48]. Among the various optically active amino alcohols tested, (-i-)-e do-2-hydroxy-endo-3-aminoborn-ane (25) was effective as a chiral catalyst for the enantioselective reaction. Treatment of the P-ketoester of 2-methyl-1-indanone 58 with a catalytic amount of the amino alcohol 25 (0.3 equiv) and 5% Pd on charcoal (0.025 equiv) under bubbling of hydrogen at 21 °C gave the (P)-enriched product 59 with 60% ee... 

Nucleophilic substitution of a (R)-methoxyisopropanol derivative (Fig. 3). Here, the proposed key step was the enantioselective hydrogenation of methoxyace-tone in analogy to the Vt-Cinchona catalyzed hydrogenation of a-ketoesters [11] (the Ru-binap system was not yet known at that time). The nucleophilic substitution with clean inversion was expected to be difficult. 

Optimization of the phosphine ligands has led to high enantioselectivity in the hydrogenation of a-acetami-doacrylic esters with rhodium catalysts and of /3-ketoesters... 

The diphosphine on the left was used with a rhodium catalyst and hydrogen to reduce the dehydroamino acid derivatives. The same reduction could also be carried out with sugar-derived phosphinites, the product being obtained in 97-99% ee.84 The diphosphine on the right, or better its counterpart, in which isopropyl has replaced methyl, was used with a ruthenium catalyst and hydrogen or 2-propanol in the reductions of /3-ketoesters. 1-Acetyl-naphthalene was reduced with a ruthenium catalyst using the ligand on the left with 2-propanol (10.38) in more 99% yield and 97% ee. 

---