Keasler Kaitlyn T, Zick Mary E, Stacy Emily E, Kim Jaehwan, Lee Jung-Hoon, Aeindartehran Lida, Runčevski Tomče, Milner Phillip J
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14850, USA.
Computational Science Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
Science. 2023 Sep 29;381(6665):1455-1461. doi: 10.1126/science.adg8835. Epub 2023 Sep 28.
Fluorine is an increasingly common substituent in pharmaceuticals and agrochemicals because it improves the bioavailability and metabolic stability of organic molecules. Fluorinated gases represent intuitive building blocks for the late-stage installation of fluorinated groups, but they are generally overlooked because they require the use of specialized equipment. We report a general strategy for handling fluorinated gases as benchtop-stable solid reagents using metal-organic frameworks (MOFs). Gas-MOF reagents are prepared on gram-scale and used to facilitate fluorovinylation and fluoroalkylation reactions. Encapsulation of gas-MOF reagents within wax enables stable storage on the benchtop and controlled release into solution upon sonication, which represents a safer alternative to handling the gas directly. Furthermore, our approach enables high-throughput reaction development with these gases.
氟是药物和农用化学品中越来越常见的取代基，因为它能提高有机分子的生物利用度和代谢稳定性。氟化气体是后期安装氟代基团的直观构建模块，但它们通常被忽视，因为使用它们需要专门的设备。我们报道了一种使用金属有机框架（MOF）将氟化气体作为台面稳定的固体试剂进行处理的通用策略。气体-MOF试剂以克级规模制备，并用于促进氟乙烯基化和氟烷基化反应。将气体-MOF试剂封装在蜡中能够在台面上稳定储存，并在超声处理时可控地释放到溶液中，这是一种比直接处理气体更安全的替代方法。此外，我们的方法能够实现这些气体的高通量反应开发。
