School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
Angew Chem Int Ed Engl. 2020 May 25;59(22):8502-8506. doi: 10.1002/anie.202002246. Epub 2020 Mar 24.
There is considerable interest in incorporating fluorine into agrochemicals and pharmaceuticals to improve their biological properties. Whilst a number of methods have been reported for installing CH F and CHF groups, they are mainly limited to radical reactions, which are invariably racemic. Herein, we report the divergent, stereospecific reaction of fluoroiodomethyllithium with boronic esters to give α-fluoro-boronic esters. These unique intermediates can be readily transformed into the corresponding mono- or difluoromethylated compounds through proto- or fluorodeboronation, respectively. The use of the highly unstable fluoroiodomethyllithium was key to allowing rapid 1,2-migration over competing decomposition of the carbanion. DFT calculations informed and supported the experimental findings.
人们对将氟原子引入农药和药物中以改善其生物特性很感兴趣。虽然已经报道了许多用于安装 CHF 和 CHF 基团的方法，但它们主要限于自由基反应，而这些反应总是外消旋的。在此，我们报告了氟碘甲基锂与硼酸酯的发散、立体特异性反应，生成了α-氟代硼酸酯。这些独特的中间体可以很容易地通过原代或氟代脱硼反应分别转化为相应的单或二氟甲基化化合物。使用高度不稳定的氟碘甲基锂是允许碳负离子快速 1,2-迁移而不是竞争分解的关键。DFT 计算为实验结果提供了信息和支持。
