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

• Published in: Journal of fluorine chemistry Vol. 130; no. 6; pp. 600 - 603
• Main Authors: Fuglseth, Erik, Sundby, Eirik, Hoff, Bård H.
• Format: Journal Article
• Language: English
• Published: LAUSANNE Elsevier B.V 01.06.2009; Elsevier
• Subjects: 1-Aryl-2-fluoroethanols; Asymmetric transfer hydrogenation; Chemistry; Chemistry, Inorganic & Nuclear; Chemistry, Organic; Physical Sciences; Ruthenium; Science & Technology; TsCYDN; TsDPEN; α-Fluoroacetophenone; Ruthenium; TsCYDN; α-Fluoroacetophenone; Asymmetric transfer hydrogenation; 1-Aryl-2-fluoroethanols; TsDPEN; alpha-Fluoroacetophenone; AROMATIC KETONES; REDUCTION; COMPLEXES; FLUORINE; ENANTIOSELECTIVE TRANSFER HYDROGENATION; WATER
• ISSN: 0022-1139; 1873-3328
• DOI: 10.1016/j.jfluchem.2009.03.011

The asymmetric transfer hydrogenation of para-substituted α-fluoroacetophenones using ruthenium based chiral catalysts gave the ( S)-1-aryl-2-fluoroethanols in ee ranging from 85–97.5%. 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%.