College of Pharmacy, Jinhua Polytechnic, Jinhua 321007, People's Republic of China.
Jinhua Branch, Sichuan Industrial Institute of Antibiotics, Chengdu University, Jinhua 321007, People's Republic of China.
J Org Chem. 2022 Aug 5;87(15):9797-9805. doi: 10.1021/acs.joc.2c00854. Epub 2022 Jul 20.
The combination of the radical chemistry of ligand-to-metal charge transfer with metal catalysis by a single iron salt helps to realize the visible-light-promoted N-H alkylation of amides and -heterocycles. A wide variety of amides and nitrogen-containing heterocycles were tolerated in our protocol to give -alkylated products. The applicability of this protocol was further demonstrated by late-stage alkylation of N-H-containing pharmaceuticals. Moreover, N-H-alkylated α-amino tetrahydrofurans could be transformed into versatile ring-opened amino alcohols under reducing conditions. A mechanistic study revealed that hydrogen atom transfer by a -butoxyl radical and a chlorine radical was responsible for the activation of C(sp)-H precursors.
配体到金属电荷转移的自由基化学与单一铁盐的金属催化相结合，有助于实现可见光促进的酰胺和杂环的 N-H 烷基化。在我们的方案中，各种酰胺和含氮杂环都能耐受，从而得到 - 烷基化产物。该方案的适用性通过含 N-H 的药物的后期烷基化进一步证明。此外，在还原条件下，N-H- 烷基化的 α-氨基四氢呋喃可以转化为多功能的开环氨基醇。一项机理研究表明， - 丁氧基自由基和氯自由基的氢原子转移负责 C(sp)-H 前体的活化。
