Wan Yanjun, Ramírez Emmanuel, Ford Ayzia, Zhang Harriet K, Norton Jack R, Li Gang
Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, Utah 84322, United States.
Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, United States.
J Am Chem Soc. 2024 Feb 21;146(7):4985-4992. doi: 10.1021/jacs.3c14481. Epub 2024 Feb 6.
Unsaturated amides represent common functional groups found in natural products and bioactive molecules and serve as versatile synthetic building blocks. Here, we report an iron(II)/cobalt(II) dual catalytic system for the syntheses of distally unsaturated amide derivatives. The transformation proceeds through an iron nitrenoid-mediated 1,5-hydrogen atom transfer (1,5-HAT) mechanism. Subsequently, the radical intermediate undergoes hydrogen atom abstraction from vicinal methylene by a cobaloxime catalyst, efficiently yielding β,γ- or γ,δ-unsaturated amide derivatives under mild conditions. The efficiency of Co-mediated HAT can be tuned by varying different auxiliaries, highlighting the generality of this protocol. Remarkably, this desaturation protocol is also amenable to practical scalability, enabling the synthesis of unsaturated carbamates and ureas, which can be readily converted into various valuable molecules.
不饱和酰胺是天然产物和生物活性分子中常见的官能团，也是用途广泛的合成砌块。在此，我们报道了一种用于合成远端不饱和酰胺衍生物的铁（II）/钴（II）双催化体系。该转化过程通过铁氮宾介导的1,5-氢原子转移（1,5-HAT）机制进行。随后，自由基中间体通过钴肟催化剂从邻位亚甲基夺取氢原子，在温和条件下高效生成β,γ-或γ,δ-不饱和酰胺衍生物。通过改变不同的助剂可以调节钴介导的氢原子转移效率，突出了该方法的通用性。值得注意的是，这种去饱和方法也适用于实际放大生产，能够合成不饱和氨基甲酸酯和脲，它们可以很容易地转化为各种有价值的分子。
