Late-stage fluorination of bridged scaffolds: Chemoselective generation of a CHF group at three positions of the bicyclo[3.3.1]nonane system

Abstract Monofluorobicyclo[3.3.1]nonane derivatives were prepared by late-stage fluorination, often proceeding with control of stereochemistry. Introduction of fluorine at the 3-, 6- or 7-position was achieved chemoselectively, the bicyclo system being constructed by a tandem one-pot Michael-aldol annulation. The major conformer was deduced for each of the fluorobicyclo compounds prepared, each possessing a unique C F orientation on a common rigid bridged scaffold that can be polysubstituted.