Chemo and enantioselective hydrogenation of fluorinated ketones on platinum modified with (R)-1-(1-naphthyl)ethylamine derivatives

The application range of platinum modified by new synthetic chiral amines was investigated in the enantioselective hydrogenation of α,α,α-trifluoromethyl ketones to the corresponding chiral alcohols. High-throughput screening was used to study the transformation of eight different substrates over a 5 wt.% Pt/Al2O3 catalyst chirally modified by eight derivatives of (R)-1-(1-naphthyl)ethylamine. The chiral modifiers possessed the same anchoring moiety (naphthalene ring) that allows strong adsorption on the Pt surface and the surroundings of the basic N atom was varied systematically. All modifiers improved the chemoselectivity to hydrogenation of the activated carbonyl group. The yield achieved in 2 h varied in a broad range (2-100%) and the modifiers had no clear positive or negative influence on the rate of the unmodified reaction. The best modifier pantoyl-naphthylethylamine (H) afforded better than 99% chemoselectivity and 90% enantiomeric excess (ee) (at 5% conversion in 2 h) in the hydrogenation of 1,1,1-trifluoro-5,5-dimethyl-2,4-hexanedione (1). Critical parameters of the reactions were the nature of solvent and catalyst pretreatments. This new catalyst system provided far better enantioselectivities than the commonly used cinchonidine-modified Pt.