Keto esters hydrogenation

Enantioselective Ketone and / -Keto Ester Hydrogenations (Including Mechanisms)... 

Random screening is usually too time consuming but a certain randomness is desirable during the exploratory phase because unexpected effects are bound to occur. Again a citation Tai [1] says regarding the discovery of the Ni/tartrate/NaBr catalyst and its application to p-keto ester hydrogenation "It was sheer luck that methyl acetoacetate was employed as a substrate...". 

Scheme 1 a The [2 + 2] cycloaddition product of prochiral trans 2-butene with Si dimers of the Si(100) surface leads to chiral adsorbate complexes, b Hydrogenation of prochiral a-keto esters over platinum is a heterogeneously catalyzed reaction leading to chiral alcohols. Using cinchonidin as chiral modifier makes this surface reaction enantioselective. In a similar fashion, TA-modified nickel is a highly enantioselective catalyst for /3-keto ester hydrogenation... 

Given the importance of [l-hydroxy esters as versatile chiral building blocks in organic synthesis and medicinal chemistry, further development of this p-keto ester hydrogenation process continues. 

Collier P.J., Goulding T., Iggo J.A. and Whyman R. (1995) Studies of the Pt-cinchona alkaloid catalyst for enantioselective alpha-keto esters hydrogenation, in Jannes G. and Dubois V. (eds.). Chiral Reactions in Heterogeneous Catalysis, Plenum Press, N.Y. p. 105-110. 

Catalytic hydrogenation of a-keto-esters can be achieved in the presence of homogeneous neutral Rh complexes of the Wilkinson type. Asymmetric reduction occurs when chiral bis-phosphines are employed as ligands, and one of the best optical yields known for homogeneous a-keto-ester hydrogenation (76%) is observed with (20a) as a ligand and propyl pyruvate as substrate. Use of the ligand (20b) increases the lipophilicity of such rhodium catalysts, and hence their solubility in non-polar solvents. ... 

Ohkuma T, Noyori R. Enantioselective ketone and (3-keto ester hydrogenations (including mechanisms) In Vries JG, Elsevier CJ, editors. Handbook of homogeneous hydrogenation. Wenheim Wiley-VCH 2007. p 1105-1164. 

---