Pd-Catalyzed Cascade Heck/C(sp3)-H Activation for Spirocyclopropyl Oxindoles.

Abstract

We have demonstrated a Pd(0)-catalyzed Heck/C(sp3)-H activation cascade for the synthesis of spirocyclopropyl oxindoles in high yields from easily accessible ortho-bromoacrylamides. The formation of spirocyclopropyl oxindole is guided by an unconventional four-membered palladacycle through C(sp3)-H activation. The reaction exhibits a wide range of substrate scope and operates efficiently with a mere 0.5 mol % of Pd-catalyst. In addition, the use of microwave conditions facilitates rapid completion of the reaction. Furthermore, this spirocyclopropanation strategy can be coupled with [3 + 2] cycloaddition to produce spiropyrrolidine oxindoles, offering a valuable approach for the preparation of alkaloids such as (±)-horsfiline and (±)-coerulescine.