Zheng Hanliang, Li Zhen, Jing Jianfang, Xue Xiao-Song, Cheng Jin-Pei
State Key Laboratory of Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China.
Center of Basic Molecular Science, Department of Chemistry, Tsinghua University, Beijing, 100084, China.
Angew Chem Int Ed Engl. 2021 Apr 19;60(17):9401-9406. doi: 10.1002/anie.202015614. Epub 2021 Mar 17.
Fluorine incorporation into organic molecules is expected to lower the pK of neighboring functionality via its strong electron-withdrawing effect, and this strategy has been widely exploited in diverse disciplines. Herein, we report a striking anomalous α-fluorine substitution effect on the α-C -H acidity. We have experimentally measured the pK values of a series of popular nucleophilic monofluoromethylating reagents α-fluoro(phenylsulfonyl)methane derivatives as well as their C-H analogues by Bordwell's overlapping indicator method in dimethyl sulfoxide solution. Contrary to expectations, we found that α-fluorine substituent does not generally enhance but rather weaken the α-C -H acidity of most (phenylsulfonyl)methane derivatives. DFT computations reproduce and provide insight into the anomalous α-fluorine effect. A correlation was identified between the C-H pK of (phenylsulfonyl)methane derivatives and Mayr's nucleophilicity parameter (N) of the corresponding carbanions.
由于氟具有很强的吸电子效应，将氟引入有机分子有望降低相邻官能团的pK值，这一策略已在多个学科中得到广泛应用。在此，我们报道了一种关于α-氟取代对α-C-H酸度的显著异常效应。我们通过Bordwell重叠指示剂法在二甲亚砜溶液中实验测定了一系列常见的亲核单氟甲基化试剂α-氟（苯磺酰基）甲烷衍生物及其C-H类似物的pK值。与预期相反，我们发现α-氟取代基通常不会增强大多数（苯磺酰基）甲烷衍生物的α-C-H酸度，反而会使其减弱。密度泛函理论（DFT）计算重现了这种异常的α-氟效应并提供了相关见解。我们确定了（苯磺酰基）甲烷衍生物的C-H pK与相应碳负离子的迈尔亲核性参数（N）之间的相关性。
