Catalytic asymmetric nucleophilic fluorination using BF₃·Et₂O as fluorine source and activating reagent

Fluorination using chiral catalytic methods could result in a direct access to asymmetric fluorine chemistry. However, challenges in catalytic asymmetric fluorinations, especially the longstanding stereochemical challenges existed in BF₃·Et₂O-based fluorinations, have not yet been addressed. Here we report the catalytic asymmetric nucleophilic fluorination using BF₃·Et₂O as the fluorine reagent in the presence of chiral iodine catalyst. Various chiral fluorinated oxazine products were obtained with good to excellent enantioselectivities (up to >99% ee) and diastereoselectivities (up to >20:1 dr). Control experiments (the desired fluoro-oxazines could not be obtained when Py·HF or Et₃N·3HF were employed as the fluorine source) indicated that BF₃·Et₂O acted not only as a fluorine reagent but also as the activating reagent for activation of iodosylbenzene.