Asymmetric reduction of 4¿-substituted _a-fluoroacetophenones

Chiral and fluorinated chemicals play an important role in modern pharmaceutical science. We are currently examining the potential of alpha-fluoracetophenones as starting materials for enantiopure finechemicals and drugs. Structurally related compounds have recently been incorporated in biologically active compunds. A series of 4´substituted alpha-fluoroacetophenones (2a-h) have been synthesised in moderate to good yields through electrophilic fluorination starting with the corresponding acetophenones 3a-h. The asymmetric reduction of the prochiral ketones have been investigated using different catalytic systems . The best results were accomplished with the proline based (R)-MeCBS catalyst, yielding the (R)-aøcohols 1a-h in high yields and excellent enantiomeric excess. Asymmetric reduction using Baker yeast (Saccharomyces cerevisiae) and Geotrichum candidum also reduced the alpha-fluoroacetophenones with high selectivity for the R-enantiomer.