Aminoketones, asymmetric hydrogenation

The reductive amination of ketones can be carried out under hydrogen pressure in the presence of palladium catalysts. However, if enantiopure Q -aminoketones are used, partial racemization of the intermediate a-amino imine can occur, owing to the equilibration with the corresponding enam-ine [102]. Asymmetric hydrogenation of racemic 2-amidocyclohexanones 218 with Raney nickel in ethanol gave a mixture of cis and trans 1,2-diamino cyclohexane derivatives 219 in unequal amounts, presumably because the enamines are intermediates, but with excellent enantioselectivity. The two diastereomers were easily separated and converted to the mono-protected cis- and trans- 1,2-diaminocyclohexanes 220. The receptor 221 has been also synthesized by this route [103] (Scheme 33). 

Asymmetric reduction The ruthenium(II)-BINAP catalysts developed by Noyori s group in 1980s were the most successful for the asymmetric hydrogenation of functionalized ketones such as a-ketoesters, a-hydroxyketones and a-aminoketones because the second... 

As an extension of this study, Hamada s group applied these conditions to the asymmetric hydrogenation of aromatic a-aminoketone hydrochlorides. Surprisingly, no reaction took place under similar conditions. However, it was discovered that the presence of a catalytic amount of NaBARF in addition to sodium acetate in toluene was essential for this hydrogenation catalysed by the same homogeneous nickel catalyst. In these adapted conditions, the synthesis of a series of anti jS-aminoalcohol hydrochlorides was achieved with moderate to high yields, almost complete anti diastereoselectivity in all cases of substrates and high enantioselectivities of up to 96% ee, as shown in Scheme 2.70. 

---