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Title: Photoredox-mediated hydroalkylation and hydroarylation of functionalized olefins for DNA-encoded library synthesis
DNA-encoded library (DEL) technology features a time- and cost-effective interrogation format for the discovery of therapeutic candidates in the pharmaceutical industry. To develop DEL platforms, the implementation of water-compatible transformations that facilitate the incorporation of multifunctional building blocks (BBs) with high C(sp 3 ) carbon counts is integral for success. In this report, a decarboxylative-based hydro alkylation of DNA-conjugated trifluoromethyl-substituted alkenes enabled by single-electron transfer (SET) and subsequent hydrogen atom termination through electron donor–acceptor (EDA) complex activation is detailed. In a further photoredox-catalyzed hydro arylation protocol, the coupling of functionalized, electronically unbiased olefins is achieved under air and within minutes of blue light irradiation through the intermediacy of reactive (hetero)aryl radical species with full retention of the DNA tag integrity. Notably, these processes operate under mild reaction conditions, furnishing complex structural scaffolds with a high density of pendant functional groups.  more » « less
Award ID(s):
1827457
PAR ID:
10300461
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ;
Date Published:
Journal Name:
Chemical Science
Volume:
12
Issue:
36
ISSN:
2041-6520
Page Range / eLocation ID:
12036 to 12045
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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