Palladium-Catalyzed Synthesis of Pyrroloisoquinolines and Isoindoles

Significance

Competitive C-H activation versus Heck reactions have been studied on 2-alkenylsubstituted o-iodobenzylpyrroles. The chemoselectivity is established by choosing the appropriate catalytic system [Pd(OAc)₂ for C-H activation, Pd(PPh₃)₄ for Heck]. The C-H activation process was extensively optimized, the Heck reaction less so. In order to rationalize the change in chemoselectivity, a ”concerted metalation-deprotonation" mechanism was proposed, based on the ability of the acetate ligand to abstract a proton from pyrrole, leading to the C-H activation product. In the absence of the acetate [catalyst: Pd(PPh₃)₄], the Heck reaction was observed.