Copper-Catalyzed Alkylation of Silyl Enol Ethers with Sterically Hindered α‑Bromocarbonyls: Access to the Histamine H3 Receptor Antagonist

A general and efficient copper-catalyzed alkylation of silyl enol ethers with functionalized alkyl bromides has been developed for the synthesis of the sterically hindered γ-ketoesters. The transformation was induced through C­(sp3)-halogen activation of commercially available sterically hindered alkyl bromides under mild conditions in good results. The strategy could be used for the synthesis of biologically active histamine H3 receptor (H3R) antagonist for medicinal purposes.