Difluorination of Furonaphthoquinones

An unprecedented difluorination reaction was developed based on the furonaphthoquinone skeleton of natural products tanshinones and their analogues. By using Selectfluor as the fluorinating source and H2O as the hydroxyl source, a wide range of unique polycyclic alpha,alpha-difluoro beta,beta-dihydroxyl para-quinone products were achieved with yields up to 90%. The mechanistic studies revealed that the reaction might undergo tandem multiple electrophilic and nucleophilic substitutions, as well as cleavages of C-O and C-C bonds. This approach not only provides a new method to synthesis of alpha,alpha-difluoro ketones, but also affords a series of unique chemotypes for biological activity screening.