Catalytic asymmetric nucleophilic fluorination using BF3·Et2O as fluorine source and activating reagent
Weiwei Zhu, Xiang Zhen, Jingyuan Wu, Yaping Cheng, Junkai An, Xingyu Ma, Jikun Liu, Yuji Qin, Hao Zhu, Jijun Xue, Xianxing Jiang
Abstract
Abstract 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 BF 3 ·Et 2 O-based fluorinations, have not yet been addressed. Here we report the catalytic asymmetric nucleophilic fluorination using BF 3 ·Et 2 O 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 Et 3 N·3HF were employed as the fluorine source) indicated that BF 3 ·Et 2 O acted not only as a fluorine reagent but also as the activating reagent for activation of iodosylbenzene.