Huihong Wang; Xiaohong Fan; Teng Chen; Yangfeng Li; Gong Zhang; Wei Fang; Yizhou Li
Org. Chem. Front., 2023, 10, 4105-4110
https://doi.org/10.1039/D3QO00901G

Abstract

Construction of DNA-encoded chemical libraries which contain focused pharmacophores is of great value for high-throughput hit discovery. Enaminone serves as a privileged scaffold in a series of bioactive compounds, and additionally as a versatile intermediate due to its reactivity for abundant diversifications. Herein, we presented a DNA-compatible amination reaction of allenic ketones to access enaminones. This synthetic approach generates enaminones in a controllable manner, thus offering a wealth of opportunities for further transformations. Meanwhile, this method exhibits a wide substrate scope with various primary or secondary amines. Further annulation transforms enaminones into unprecedented polyfunctionalized benzenes in a DNA-encoded stepwise fusion fashion, demonstrating the potential of allelic ketone synthons in DNA-encoded library construction.