DNA-compatible synthesis of enaminones via amination of allenic ketones

Abstract

Construction of DNA-encoded chemical libraries that 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 present 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 allenic ketone synthons in DNA-encoded library construction.