Enantioselective gem-Chlorofluorination of Active Methylene Compounds

Significance

Despite the interesting synthetic and bioactive potential, molecules containing gem-chlorofluorinated chiral carbon centers have not received sufficient attention, which might be due to the challenging nature of stereodifferentiation between two halogen atoms. In this paper, a highly enantioselective one-pot chlorofluorination of active methylene compounds (involving β-keto esters and β-keto phosphonates) was achieved using a copper complex of the SPYMOX ligand, first reported by Shibatomi and Iwasa (Synlett 2009, 241). The synthetic importance of the resulting products was demonstrated by diverse functionalization. Notably, routes to fluoro epoxides and fluorinated β-amino acids were established.