Department of Drug Design, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Faculty of Chemistry, Department of Crystal Chemistry and Crystal, Physics, Biocrystallography Group, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.
J Org Chem. 2022 Nov 4;87(21):14463-14475. doi: 10.1021/acs.joc.2c01905. Epub 2022 Oct 25.
We achieved a divergent synthesis of isoquinolin-2(1)-yl-acetamides (16 examples, up to 90% yields) and regioselective isoindolin-2-yl-acetamides (14 examples, up to 93% yields) in moderate to good yields by reacting various substituted ethanones or terminal alkynes with Ugi-4CR intermediates via an ammonia-Ugi-4CR/Copper(I)-catalyzed annulation sequence reaction. The same intermediate thus gives 2D distant but 3D closely related scaffolds, which can be of high interest in exploiting chemistry space on a receptor. The scopes and limitations of these efficient sequence reactions are described, as well as gram-scale synthesis.
我们通过反应各种取代的乙酮或末端炔与 Ugi-4CR 中间体，经氨-Ugi-4CR/铜（I）催化的环加成序列反应，以中等至良好的收率实现了异喹啉-2(1)-基-乙酰胺（16 个实例，最高达 90%收率）和区域选择性异吲哚啉-2-基-乙酰胺（14 个实例，最高达 93%收率）的发散合成。相同的中间体因此提供了 2D 上相隔但 3D 上紧密相关的支架，这在受体上探索化学空间时可能具有很高的兴趣。这些高效序列反应的范围和限制以及克级合成也进行了描述。
