Regioselective synthesis of spirocyclic pyrrolines via a palladium-catalyzed Narasaka–Heck/C–H activation/[4 + 2] annulation cascade reaction

Abstract

A novel palladium-catalyzed spirocyclization through sequential Narasaka–Heck cyclization, C–H activation and [4 + 2] annulation has been developed. In this reaction, cheap and readily available 2-chlorobenzoic acid or ethyl phenylpropiolate was employed as the C2 insertion unit to react with γ,δ-unsaturated oxime ester. The key step in this transformation is the regioselective insertion of the C2 synthon into the spiro-palladacycle intermediate that is formed by the δ-C–H activation process, thereby efficiently assembling a series of spirocyclic pyrrolines with high regiocontrol. Furthermore, density functional theory (DFT) calculations and control experiments were performed to gain some insights into the reaction mechanism.