Carbon Dioxide Activation Center (CADIAC), The Interdisciplinary Nanoscience Center (iNANO) and, Department of Chemistry, Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.
Chemistry. 2022 Jun 15;28(34):e202200997. doi: 10.1002/chem.202200997. Epub 2022 May 3.
An expedient ex-situ generation of difluoroiodomethane (DFIM) and its immediate use in a Pd-catalyzed difluoromethylation of aryl boronic acids and ester derivatives in a two-chamber reactor is reported. Heating a solution of bromodifluoroacetic acid with sodium iodide in sulfolane proved to be effective for the generation of near stoichiometric amounts of DFIM for the ensuing catalytic coupling step. A two-step difluoromethylation of aryl (pseudo)halides with tetrahydroxydiboron as a low-cost reducing agent, both promoted by Pd catalysis, proved effective to install this fluorine-containing C group onto several pharmaceutically relevant molecules. Finally, the method proved adaptable to deuterium incorporation by simply adding D O to the DFIM-generating chamber.
本文报道了一种简便的二氟碘甲烷（DFIM）的异位生成方法，并将其立即用于在双室反应器中钯催化的芳基硼酸和酯衍生物的二氟甲基化反应中。研究发现，将溴二氟乙酸与碘化钠在环丁砜中加热，可有效地生成近化学计量的 DFIM，用于随后的催化偶联步骤。使用四氢二羟基二硼作为低成本还原剂，通过两步法对芳基（假）卤化物进行二氟甲基化，同时促进钯催化，可有效地将该含氟 C 基团引入到几种具有药用价值的分子中。最后，通过简单地将 D2O 添加到 DFIM 生成室中，该方法可适应氘的掺入。
