A Chemistry for Incorporation of Selenium into DNA-Encoded Libraries

Abstract

Conventional direct C-H selenylation suffers from simple selenation with limited atom economy and complicated reaction system. In this work, we designed benzoselenazolone as a novel bifunctional selenide reagent for both off- and on-DNA C-H selenylation under rhodium(III) catalysis. We show that using benzoselenazolone allowed production of a series of selenylation products containing an adjacent aminoacyl group in a fast and efficient way, with high atom economy. The synthetic application of this method was demonstrated by taking advantage of the amide functionality as a nucleophile, directing group, and amide coupling partner. This work shows great potential in facilitating rapid construction of selenium-containing DNA-encoded chemical libraries (SeDELs), and lays the foundation for the development of selenium-containing drugs.

Keywords: C−H activation; DNA-encoded library; benzoselenazolone; rhodium; selenylation.