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.

DNA-encoded libraries (DELs): a review of on-DNA chemistries and their output

“…After optimization, they transferred the method to on-DNA reaction ( Table 4 entry 12). 62 The DNA-tagged indole derivatives reacted with benzoselenazolones, which were substituted with halogen ( i.e. , F, Cl, and Br) and methoxy in phosphate buffer–DMA (7 : 1) under (RhCp * [MeCN] 3 [SbF 6 ] 2 ) catalysis.…”

“…Except C-C coupling, the construction of C-N bond was mediated by nickel catalyst. The DNA linked phenyl iodine could62 The DNA-tagged indole derivatives reacted with benzoselenazolones, which were substituted with halogen (i.e., F, Cl, and Br) and methoxy in phosphate buffer-DMA (7 : 1) under (RhCp * [MeCN] 3[SbF 6…”

Transition-metal-free decarboxylative thiolation of stable aliphatic carboxylates

“…Based on the success of the decarboxylative C–S bond formation in this protocol and the similar reactivity in construction of C–Se bonds, 19 we further investigated the reactions of diphenyl diselenide with stable aliphatic carboxylates to generate related aryl selenide scaffolds ( Table 4 ), which are widely applied in antioxidants, fluorescent probes, and functional organic materials. 20 To our delight, both (hetero)aryl acetates and α-CN substituted acetates underwent decarboxylative cross-coupling of diphenyl diselenide under the standard reaction conditions described above, providing a simple general approach to synthesize a diverse range of organoselenium compounds.…”

In-solution direct oxidative coupling for the integration of sulfur/selenium into DNA-encoded chemical libraries

“…17 Moreover, Zhang and Lu reported an on-DNA transition-metal free aryl-S bond formation by using novel aryl ammonium building blocks through the S N Ar process. 18 For on-DNA selenylation, to the best of our knowledge, there are only two seminal reports from the groups Lerner and Yang 19 and Zhang, 20 respectively, where the former achieved Rh-catalyzed C-H functionalization via bifunctional benzoselenazolone and the latter achieved radical selenylation through a heterogeneous solid support-mediated on-DNA strategy (see path C in Fig. 1b).…”