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

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 gamma,delta-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 delta-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.

Automated summary

A novel palladium-catalyzed spirocyclization method has been developed through sequential Narasaka-Heck cyclization, C-H activation and [4 + 2] annulation. This method utilizes cheap and readily available compounds to react with gamma,delta-unsaturated oxime ester, achieving high regioselectivity in the spirocyclization reaction.