Synthesis of medicinally relevant oxalylamines via copper/Lewis acid synergistic catalysis.

Wu, Ziying; Hu, Miao; Jin, Yangbin; Li, Jianxiao; Wu, Wanqing; Jiang, Huanfeng · Sci Adv · 2021

basic_science · Level V

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Abstract

Allylamines have long been recognized as valuable synthons because of their excellent reactivity in organic synthesis. Her<b>e,</b> an efficient amination reaction of allenyl ethers via copper/Lewis acid synergistic catalysis has been established, providing straightforward access to diverse functionalized <i>Z</i>-oxalylamines and <b><i>E</i></b> -halogenated oxalylamines in good to excellent yields with high regio- and stereoselectivities. The developed method tolerates more than 100 examples that include late-stage functionalization of bioactive molecules, and features gram-scale synthesis of oxalylamines with high turnover number (TON > 1000) under mild and simple conditions. The applicability of the protocol is further demonstrated with the construction of drug molecules.