Borane‐Mediated Highly Secondary Selective Deoxyfluorination of Alcohols

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Organofluorine compounds are vital across multiple sectors, hence highly selective methods to install fluorine are of considerable importance. The deoxyfluorination of alcohols is a key approach to prepare organofluorine compounds, however, a highly secondary (2°)‐selective deoxyfluorination of alcohols has not been realized to date. Herein, we report that borane‐mediated deoxyfluorination results in high 2°‐selectivity in inter‐ and intra‐molecular competition reactions versus primary (1°), tertiary (3°) and even benzylic (Bn) alcohols. This is an operationally simple method using only commercial reagents (e.g., Et 3 N ⋅ 3HF) that starts from the alcohol which is converted to the O ‐alkyl‐ N ‐H‐isourea in situ. The origin of the high 2°‐selectivity was elucidated to be due to the relative barriers to carbodiimide elimination from the O ‐alkyl‐ N ‐(BR 2 )‐isoureas. As the selectivity controlling step does not involve fluoride, this borane‐mediated approach can be applied to other nucleophiles, as demonstrated by 2°‐selective deoxychlorination using HCl occurring in preference to substitution of 1° and Bn analogues. This borane‐mediated nucleophilic substitution therefore provides a new approach to circumvent the selectivity limitations inherent in classical S N 2 and S N 1 type reactions.