Catalytic asymmetric nucleophilic fluorination using BF<sub>3</sub>·Et<sub>2</sub>O as fluorine source and activating reagent.

Zhu, Weiwei; Zhen, Xiang; Wu, Jingyuan; Cheng, Yaping; An, Junkai; Ma, Xingyu; Liu, Jikun; Qin, Yuji et al. · Nat Commun · 2021

basic_science · Level V

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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<sub>3</sub>·Et<sub>2</sub>O-based fluorinations, have not yet been addressed. Here we report the catalytic asymmetric nucleophilic fluorination using BF<sub>3</sub>·Et<sub>2</sub>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<sub>3</sub>N·3HF were employed as the fluorine source) indicated that BF<sub>3</sub>·Et<sub>2</sub>O acted not only as a fluorine reagent but also as the activating reagent for activation of iodosylbenzene.