Ruthenium-catalysed asymmetric transfer hydrogenation of para-substituted α-fluoroacetophenones

Abstract

The first examples of asymmetric transfer hydrogenation of α-fluoroacetophenones are reported. Eight para-substituted α-fluoroacetophenones have been reduced using four catalytic systems constructed of [RuCl 2( p-cymene) 2] 2 or [RuCl 2(mesitylene) 2] 2 in combinations with each of the ligands (1 R,2 R)- N-( p-toluenesulfonyl)-1,2-diphenylethylenediamine (( R, R)-TsDPEN) and (1 R,2 R)- N-( p-toluenesulfonyl)-1,2-cyclohexanediamine (( R, R)-TsCYDN). All reactions were performed in both water and formic acid/triethylamine. The highest enantioselectivity was obtained using the ( R, R)-TsDPEN ligand in a formic acid/triethylamine mixture, giving the ( S)-1-aryl-2-fluoroethanols in high to moderate enantiomeric excess (97.5–84.5%). For this solvent system the presence of electron withdrawing groups in the para position reduced the enantioselectivity. Reactions performed in water generally gave lower enantioselectivity and reaction rate, although RuCl(mesitylene)-( R, R)-TsDPEN yielded the product alcohols with enantiomeric excess in the range of 95.5–76.5%.