Palladium-Catalyzed Benzylation/Semipinacol Rearrangement for the Construction of 3-Quaternary Carbon 2-Spiroindoline

Abstract

The 3-quaternary carbon 2-spiroindoline scaffold occupies a significant position in both medicinal and synthetic chemistry. While the dearomatization of indoles represents the most direct and efficient route to such structural units, considerable limitations persist. Herein, utilizing 2-cyclobutanol-3-substituted indoles and benzyl phosphates as model substrates, we developed a novel Pd/BEt₃ synergistic catalyzed tandem benzylation/semipinacol rearrangement. This strategy efficiently constructs a series of 3-quaternary carbon 2-spiroindolines in high yields with excellent chemoselectivity and diastereoselectivity. Furthermore, this catalytic cascade reaction proceeds efficiently in a one-pot manner, as the thermally driven semipinacol rearrangement circumvents the need for intermediate isolation.