Yang Yuhao, Hammond Gerald B, Umemoto Teruo
Department of Chemistry, University of Louisville, Louisville, KY 40292, USA.
Angew Chem Int Ed Engl. 2022 Oct 24;61(43):e202211688. doi: 10.1002/anie.202211688. Epub 2022 Sep 26.
Fluorination of carbanions is pivotal for the synthesis of fluorinated compounds, but the current N-F fluorinating agents have significant drawbacks due to many reactive locations that surround the reactive N-F site. By developing a sterically hindered N-fluorosulfonamide reagent, namely N-fluoro-N-(tert-butyl)-tert-butanesulfonamide (NFBB), we discovered a conceptually novel base-catalyzed, self-sustaining fluorination of active methylene compounds and achieved the high-yielding fluorination of the hitherto difficult highly basic (hetero)aryl and alkenyl lithium species. In the former, the mild and high yield fluorination of active methylene compounds exhibited wide functional group tolerance and its novel catalytic fluorination-deprotonation cycle mechanism was demonstrated by deuterium-tracing experiments. In the latter, NFBB reacted with a variety of highly basic (hetero)aryl and alkenyl lithium species to provide the desired fluoro (hetero)arenes and alkenes in unprecedented high or quantitative yields.
碳负离子的氟化反应对于含氟化合物的合成至关重要，但目前的N-F氟化剂存在显著缺点，因为在反应性N-F位点周围存在许多反应活性位置。通过开发一种空间位阻较大的N-氟磺酰胺试剂，即N-氟-N-(叔丁基)-叔丁烷磺酰胺（NFBB），我们发现了一种概念上新颖的碱催化、自维持的活性亚甲基化合物氟化反应，并实现了对迄今为止难以氟化的高碱性（杂）芳基和烯基锂物种的高产率氟化反应。在前一种反应中，活性亚甲基化合物的温和且高产率氟化反应表现出广泛的官能团耐受性，并且通过氘追踪实验证明了其新颖的催化氟化-去质子化循环机制。在后一种反应中，NFBB与多种高碱性（杂）芳基和烯基锂物种反应，以前所未有的高收率或定量收率提供所需的氟代（杂）芳烃和烯烃。
