Functionalization of DNA-Tagged Alkenes with Diazo Compounds via Photocatalysis

Abstract

To explore potential chemical space using DNA-encoded library (DEL) technology, the development of various types of robust DNA-compatible reactions is urgently needed. Diazo compounds, which serve as valuable building blocks and important synthons in synthetic chemistry, have been rarely applied in DEL synthesis, probably because of their potential modifications of the bases and phosphate backbone of DNA. Herein we report two cases of DNA-compatible reactions with alkenes and diazo compounds, providing corresponding hydroalkylation and cyclopropanation products in moderate to excellent yields. Notably, these transformations not only provide new access to C(sp 3 )−C(sp 3 ) bond formation in DELs with excellent functional group tolerance but also represent practical ligation methods to introduce functionalized molecules into DNA.

Ru-Catalyzed Hydrogen Atom Transfer/C–F Bond Cleavage of Difluoroalkyl Diazos with Hantzsch Ester via a Photocatalytic Radical Process

“…Hantzsch ester (HE) has been well-applied in photoredox reactions as terminal reductants affording a hydride, electron, and hydrogen atom . HE is readily available and high stability; thus, it could be an ideal reagent as a sacrificial single-electron donor and hydrogen atom donor during the conversion of diazo compounds to carbon radical species . In 2020, Doyle and co-authors reported an elegant photocatalytic radical reaction of diazo compounds with alkenes in the presence of HE .…”

Copper-Mediated Three-Component Reaction for the Synthesis of N-Acylsulfonamide on DNA

“…As a result, reactions carried out under conventional heating conditions with low or high pH are limited for the preparation of DNA-conjugated compounds. Moreover, because negative charges of phosphates in the DNA backbone exhibit a metal-chelation effect, the application of recently developed transition metal catalysis is problematic. , For this reason, the development of a reaction for constructing a DNA-encoded library (DEL) capable of introducing a novel functional group is required to extend the versatility of current technologies. − …”

Vinyl azide as a synthon for DNA-compatible divergent transformations into N-heterocycles

“…25–30 While DNA liability to stringent conditions hampers its application in conventional organic synthesis, 31,32 a variety of DNA-compatible reactions have still been successfully developed in recent years to expand the structural complexity of encoded chemical libraries. 33–40…”

“…[25][26][27][28][29][30] While DNA liability to stringent conditions hampers its application in conventional organic synthesis, 31,32 a variety of DNA-compatible reactions have still been successfully developed in recent years to expand the structural complexity of encoded chemical libraries. [33][34][35][36][37][38][39][40] Diversity-oriented synthesis (DOS) represents a fast approach for generating distinct structures based on the uniform intermediate, which is in accordance with the DEL concept. [41][42][43] More structural diversity would undoubtedly increase the chemical space and broaden the structural complexity of the library.…”