Shen Li-Wen, Li Ting-Ting, You Yong, Zhao Jian-Qiang, Wang Zhen-Hua, Yuan Wei-Cheng
National Engineering Research Center of Chiral Drugs, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, 610041, China.
Institute for Advanced Study, Chengdu University, Chengdu 610106, China.
J Org Chem. 2021 Sep 3;86(17):11472-11481. doi: 10.1021/acs.joc.1c00993. Epub 2021 Aug 3.
An efficient inverse electron-demand aza-Diels-Alder reaction of cyclic enamides and 1,2-diaza-1,3-dienes, which could be readily formed in situ from α-halogeno hydrazones and a base, has been successfully developed. With the developed approach, a wide range of fused polycyclic tetrahydropyridazines were smoothly obtained in up to 99% yield under benign reaction conditions. This reaction concept was also extended to acyclic enamide substrates for accessing 1,4,5,6-tetrahydropyridazines. A gram-scale experiment and further derivatizations of the polycyclic tetrahydropyridazine products were also conducted to verify the practicability of the methodology.
已成功开发出一种环状烯酰胺与1,2-二氮杂-1,3-二烯的高效逆电子需求氮杂-狄尔斯-阿尔德反应，1,2-二氮杂-1,3-二烯可由α-卤代腙和碱原位轻松生成。采用该方法，在温和的反应条件下，可顺利获得各种稠合多环四氢哒嗪，产率高达99%。该反应概念还扩展到无环烯酰胺底物，用于合成1,4,5,6-四氢哒嗪。还进行了克级实验以及多环四氢哒嗪产物的进一步衍生化，以验证该方法的实用性。
