Heterogeneous Catalytic Enantioselective Hydrogenation of Activated Ketones

Abstract

The manuscript gives an overview mainly on the results performed at the Department of Organic Chemistry the University of Szeged on the enantioselective hydrogenation of activated ketones of various structures on Pt/alumina catalysts modified with cinchona alkaloids. Relevant results by other research groups are also referred too. The review covers the literature till the end of 2004.

Asymmetric cascade reaction of 2-nitrophenylpyruvates over chirally modified platinum catalyst

“…Similarly, Pt catalysts modified by cinchona alkaloids have been successfully applied for the enantioselective hydrogenation of several activated ketones, such as -ketoesters,-ketoacids, -ketoamides, -diketones, -keto acetals, -ketoethers, trifluoromethyl ketones, ketopantolactone, and others [42][43][44][45]. However, most of the knowledge about this catalytic system has been collected using the enantioselective hydrogenation of methyl or ethyl pyruvate and benzoate, originally reported by Orito and co-workers (Scheme 7) [46,47].…”

“…Based on the stereochemistry of the hydrogenations of -keto esters investigated up to now over Pt modified by CD [42][43][44][45], we assumed that the use of alkaloids from this series results in excess formation of the product enantiomer having R absolute configuration. However, the configuration of the product was checked by reducing the purified product using LiAlH 4 to 3-hydroxy-1,2,3,4-tetrahydroquinoline with known specific rotation [106].…”

“…The solvent may have a significant effect on the hydrogenation rate of the functional groups, as well as on the ee obtained in the hydrogenation of activated ketones over Pt catalysts modified by cinchona alkaloids [42][43][44][45]. Accordingly, initially we have studied the effect of different solvents on the reaction out-come.…”

“…It is known that toluene (T) and acetic acid (AcOH), and their mixtures are the best performing and most often used in the enantioselective hydrogenation of α-keto esters over Pt catalysts modified with cinchona alkaloids [42][43][44][45]. Therefore, we decided to investigate the reaction in T and T with addition of small amount of AcOH, which was used because of low solubility of some products in pure T. On the other hand, the indole (3) selectivity increased to 38% in pure AcOH (not shown in Table 1).…”

“…The best result was obtained using dHMCD (dihydrocinchonidine methyl ether) as modifier, although cinchona alkaloid methyl ethers provided better results as compared with the parent alkaloids in both cinchona series (C 8 S-C 9 R and C 8 R-C 9 S). Based on the stereochemistry of the hydrogenations of -keto esters investigated up to now over Pt modified by CD [42][43][44][45]119,120] we supposed that the use of alkaloids from this series results in excess formation of the R enantiomer. The configuration of the product was checked by reducing the product formed in the cascade reaction of ethyl 2-nitrophenylpyruvate with LiAlH 4 to 3-hydroxy-1,2,3,4-tetrahydroquinoline with known specific rotation [106].…”