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.本研究开发了一种通用且高效的铜催化硅烯醇醚（silyl enol ethers）与官能化烷基溴的烷基化反应，用于合成位阻较大的γ-酮酯。该转化通过市售位阻烷基溴的C(sp3)-卤键活化引发，在温和反应条件下即可获得良好的反应结果。此策略可用于合成具有生物活性的组胺H3受体（histamine H3 receptor, H3R）拮抗剂，以满足药用需求。