Late-Stage Functionalization Using a Popular Titrating Agent: Aryl-Chlorides and -Fluorides Activation by the
Alessandro Cerveri1, Giulia Russo1, Sara Sparascio1
1Department of Chemistry, Life Sciences and Environmental Sustainability, Università di Parma, Parco Area delle Scienze 17/A, 43124, Parma, Italy.
Abstract:
Aryl-chlorides and -fluorides are common building blocks, but their use in synthesis is limited by the high stability of their Ar-X bonds. The generation of aryl radicals via activation of strong Ar-X bonds is possible through the irradiation of tailor-made organic anions, which become reductants stronger than lithium metal. We report that the combination of visible light with the cheap diphenylacetic acid dianion is an even better tool, showing excellent activity across a variety of complex substrates and providing opportunities for late-stage drug modification. Ar-X bonds are chemoselectively activated in the presence of more easily reducible functions, such as Alk-Cl ones and carbonyl groups. These results pave the way to original synthetic strategies that would be otherwise considered impossible.
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