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

The first examples of asymmetric transfer hydrogenation of alpha-fluoroacetophenones are reported. Eight para-substituted a-fluoroacetophenones have been reduced using four catalytic systems constructed of [RuCl2(p-cymene)(2)](2) or [RuCl2(mesitylene)(2)](2) in combinations with each of the ligands (1R,2R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine ((R,R)-TsDPEN) and (1R,2R)-N-(p-toluenesulfonyl)-1,2cyclohexanediamine ((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%. (c) 2009 Elsevier B.V. All rights reserved.