Generation of Tertiary and Quaternary Stereocenters via Palladium-Catalyzed Intramolecular Heck-type Reactions for the Stereocontrolled Synthesis of Pyrrolo[1,2-b]isoquinolines

Abstract

The generation of quaternary and tertiary stereocenters on C-10 of the pyrroloisoquinoline skeleton through intramolecular Mizoroki-Heck reactions of 2-alkenyl substituted pyrroles and pyrrolidines has been studied. The cyclizations proceeded with moderate to good yields (up to 81%), although with low enantioselection when chiral phosphanes, such as (R)-BINAP, are used as ligands. However, enantiomerically pure 10-substituted pyrrolo[1,2-b]isoquinolines have been efficiently obtained through a diastereoselective approach using chiral non-racemic pyrrolidines as substrates, generating a tertiary stereocenter