Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.
Discovery Chemistry Platforms, PET Radiochemical Synthesis, Bristol-Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08543, United States.
J Am Chem Soc. 2020 May 20;142(20):9493-9500. doi: 10.1021/jacs.0c03125. Epub 2020 May 7.
We report a redox-neutral method for nucleophilic fluorination of -hydroxyphthalimide esters using an Ir photocatalyst under visible light irradiation. The method provides access to a broad range of aliphatic fluorides, including primary, secondary, and tertiary benzylic fluorides as well as unactivated tertiary fluorides, that are typically inaccessible by nucleophilic fluorination due to competing elimination. In addition, we show that the decarboxylative fluorination conditions are readily adapted to radiofluorination with [F]KF. We propose that the reactions proceed by two electron transfers between the Ir catalyst and redox-active ester substrate to afford a carbocation intermediate that undergoes subsequent trapping by fluoride. Examples of trapping with O- and C-centered nucleophiles and deoxyfluorination via -hydroxyphthalimidoyl oxalates are also presented, suggesting that this approach may offer a general blueprint for affecting redox-neutral S1 substitutions under mild conditions.
我们报告了一种使用 Ir 光催化剂在可见光照射下实现 -羟基邻苯二甲酰亚胺酯亲核氟化的氧化还原中性方法。该方法可用于合成广泛的脂肪族氟化物，包括伯、仲和苄基氟化物以及通常由于竞争消除而无法通过亲核氟化获得的未活化的叔氟化物。此外，我们表明脱羧氟化条件可轻松适应 [F]KF 的放射性氟化。我们提出反应通过 Ir 催化剂和氧化还原活性酯底物之间的两个电子转移进行，生成碳正离子中间体，随后被氟化物捕获。还提出了与 O-和 C-中心亲核试剂的捕获以及通过 -羟基邻苯二甲酰亚胺基草酸酯进行脱氧氟化的例子，这表明该方法可能为在温和条件下进行氧化还原中性 S1 取代提供了一种通用蓝图。
