Synthesis of arylated chalcone derivatives via palladium cross-coupling reactions

A useful protocol for arylation of the olefin double bond of chalcones to afford tri- and tetra-substituted chalcone derivatives is reported. The protocol begins with the Heck reaction between chalcones and aryl iodides providing beta-arylchalcones. This reaction tolerates various functional groups on both rings, as well as deactivated aryl iodides. The products are obtained in moderate to excellent yields and the (E)-beta-arylchalcones (E:Z > 96:4) can be isolated via precipitation. Competitive Heck reactions pointed to a significant effect of ring one substituents on the reaction rate, while substituents on ring two have a much smaller effect. To access alpha,beta-diarylchalcones, a sequential bromination-Suzuki cross coupling strategy was applied to the beta-arylated compounds which afforded double arylated chalcone derivatives in 60-99% yield over two steps. (C) 2018 Elsevier Ltd. All rights reserved.