Sanofi, R&D, Integrated Drug Discovery, Industriepark Höchst, 65926 Frankfurt am Main, Germany.
J Am Chem Soc. 2022 Jun 8;144(22):9997-10005. doi: 10.1021/jacs.2c03220. Epub 2022 May 25.
Introducing the novel concept of amino radical transfer (ART) enables the use of easily accessible and commercially available alkyl boronic esters as cross-coupling partners for aryl halides in dual photoredox/nickel catalysis mediated by visible light. Activation of otherwise photochemically innocent boronic esters by radicals generated from primary or secondary alkylamines gives rise to an outstanding functional group tolerance in a mild, fast, and air-stable reaction. As shown in more than 50 examples including unprotected alcohols, amines, and carboxylic acids, this reaction allows quick access to relevant scaffolds for organic synthesis and medicinal chemistry. In comparison with existing methods for C(sp)-C(sp) couplings an extraordinary generality could be realized via the ART concept, employing a single set of optimized reaction conditions. Due to its selectivity, the transformation can also be used for late-stage functionalization, as demonstrated with three exemplary syntheses of drug molecules. Furthermore, the successful one-to-one scalability of this reaction up to gram scale without the necessity of any further precautions or flow systems is demonstrated.
引入了新型的氨基自由基转移（ART）概念，使得在可见光介导的双光氧化还原/镍催化作用下，可以使用易于获得和商业上可用的烷基硼酸酯作为芳基卤化物的交叉偶联伙伴。通过自由基将原本光化学上惰性的硼酸酯激活，这些自由基来自伯胺或仲胺，可以在温和、快速且空气稳定的反应中实现出色的官能团耐受性。正如 50 多个实例所示，包括未保护的醇、胺和羧酸，该反应为有机合成和药物化学提供了快速获得相关支架的途径。与现有的 C(sp)-C(sp) 偶联方法相比，通过 ART 概念可以实现非凡的通用性，仅使用一套优化的反应条件即可实现。由于其选择性，该转化也可用于后期的功能化，通过三个药物分子的合成示例得到了证明。此外，该反应可以成功地进行一比一的放大至克级规模，而无需任何进一步的预防措施或流动系统。
