Abstract
The asymmetric reduction of eight alpha-fluoroacetophenones has been investigated using (R)-MeCBS as a catalyst in various media. Based on a solvent screen, 1,2-dimethoxyethane, diethyl ether and dichloromethane were used in reductions of the alpha-fluoroacetophenones. The enantiomeric excess of the products depended oil the solvent and the electronic character of the aromatic substituents. Higher enantioselectivity and less solvent dependency were observed in the reduction of substrates bearing electron donating substituents, whereas the opposite was the case for reduction of the substrates with electron withdrawing substituents. The (R)-2-fluoro-1-arylethanols were obtained with enantiomeric excesses in the range of 91-99% using 1,2-dimethoxyethane as a solvent. Six of the alcohols produced are new chemical entities. The absolute configurations of the (R)-2-fluoro-1-arylethanols were determined by circular dichroism using the exciton chirality method of tile (S)-benzoate esters of the alcohols. The (S)-benzoate esters were obtained by lipase-catalysed resolution using Novozym 435. (C) 2008 Elsevier Ltd. All Fights reserved.
