Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.
J Am Chem Soc. 2020 May 20;142(20):9181-9187. doi: 10.1021/jacs.0c03881. Epub 2020 May 11.
Molecular editing such as insertion, deletion, and single atom exchange in highly functionalized compounds is an aspirational goal for all chemists. Here, we disclose a photoredox protocol for the replacement of a single fluorine atom with hydrogen in electron-deficient trifluoromethylarenes including complex drug molecules. A robustness screening experiment shows that this reductive defluorination tolerates a range of functional groups and heterocycles commonly found in bioactive molecules. Preliminary studies allude to a catalytic cycle whereby the excited state of the organophotocatalyst is reductively quenched by the hydrogen atom donor, and returned in its original oxidation state by the trifluoromethylarene.
分子编辑，如在高度官能化的化合物中进行的插入、删除和单原子交换，是所有化学家的理想目标。在这里，我们披露了一种光氧化还原协议，用于在包括复杂药物分子在内的缺电子三氟甲基芳烃中用氢原子取代单个氟原子。一项稳健性筛选实验表明，这种还原脱氟能够容忍生物活性分子中常见的一系列官能团和杂环。初步研究表明存在一个催化循环，其中有机光催化剂的激发态被氢原子供体还原猝灭，并通过三氟甲基芳烃返回到其原始氧化态。
