Direct a-Fluorination of Aldehydes

Various chiral amines can catalyze the direct enantioselective a-fluorination of aldehydes. Enders and Hiittl have focused on the use of Selectfluor for the a-fluorination of aldehydes and ketones [24a], For the aldehydes, no enantiomeric excess was reported using L-proline as the catalyst. In an attempt to perform direct enantioselective a-fluorination of ketones, cyclohexanone was used as the model substrate and a number of chiral amines were tested for their enantioselective properties however, the enantiomeric excess was rather low and in the range of 0 to 36% ee. 

The direct enantioselective organocatalytic a-fluorination can also be performed with cinchona alkaloid derivatives as catalyst under phase-transfer reaction conditions [25]. The fluorination reaction by NFSI of / -ketoesters 21, readily enolizable substrates, generated a stereogenic quaternary C-F bond in high yields and with enantioselectivities up to 69% ee for the optically active products 26 (Eq. 6). 

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