Herein we report the synthesis of a series of C9-fluorinated quinine alkaloids by direct nucleophilic deoxyfluorination. This transformation gives rise to products bearing both S- and R-configured monofluoromethylene functionalities, consistent with an SN1-like mechanism. Furthermore, a series of ring-expanded 1-azabicyclo[3.2.2]nonane systems were generated by a skeletal rearrangement of the quinuclidine core. The modified alkaloids were converted to the corresponding hydrochloride salts and characterised by single-crystal X-ray diffraction analysis. The preference of the benzylic fluorine atom to adopt a gauche conformation relative to the protonated quinuclidine nitrogen atom was consistently observed throughout the cage-conserved compounds. Conversely, the molecular architecture of the 1-azabicyclo[3.2.2]nonane systems enforced an anti relationship between the fluorine atom and the protonated tertiary amine. This constitutes the first X-ray evidence of a vicinal fluorine atom at a stereogenic centre positioned anti to a substituted ammonium cation. The pharmacological efficacy of these compounds was assessed in vitro against the NF54 strain of Plasmodium falciparum (sensitive to all known antimalarial drugs). IC50 values of as low as 267 nM were observed; this highlights the potential of these materials in developing novel agents for parasite chemotherapy.